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COLOPEC: Adjuvant HIPEC for high-risk colon cancer disappoints
SAN FRANCISCO – according to primary results of the Dutch COLOPEC trial presented at the 2019 GI Cancers Symposium.
“Despite adjuvant systemic chemotherapy, locally advanced stage II and stage III colon cancer can give rise to metachronous peritoneal metastases in up to 25% of patients,” commented principal investigator Pieter J. Tanis, MD, PhD, a colorectal surgeon at the Academic Medical Center in Amsterdam. “These metastases are very difficult to detect, and when you detect them, they are difficult to treat.”
The 202 patients in COLOPEC, a multicenter, phase 3, randomized, controlled trial, underwent curative resection of primary colon tumors that were large (pT4 or cT4) or perforated, putting them at high risk for peritoneal metastases. All received routine adjuvant systemic chemotherapy.
At 18 months, the proportion of patients alive and free of peritoneal recurrence, assessed by laparoscopy, was 81% with addition of early postoperative oxaliplatin HIPEC and 76% without it, a nonsignificant difference.
“We couldn’t find any superiority of adjuvant HIPEC with oxaliplatin regarding peritoneal metastases–free survival in patients with T4 or perforated colon cancer,” Dr. Tanis summarized.
“We had a problem with the intention-to-treat analysis because 9% of patients already had recurrences before we performed the adjuvant HIPEC,” he added. “But I think we cannot perform an as-treated analysis in this trial because we don’t know the early recurrences in the control group.”
A symposium attendee wondered if the longer time to receiving systemic adjuvant systemic chemotherapy in the HIPEC group, a delay of about 4 weeks relative to the no-HIPEC group, was problematic and warranted consideration of neoadjuvant chemotherapy instead.
“The problem of the delay in chemotherapy, if you look in the literature, is there is no randomized trial looking at, for example, an 8- versus 12-week interval,” Dr. Tanis replied, noting that, in studies, adjuvant chemotherapy has most commonly been delayed because of patient comorbidities or surgical complications. “But you have to look very carefully at the expectation of the direct association between delay of chemotherapy and an effect. We have already looked at the disease-free survival and overall survival [in COLOPEC] and have not seen any difference … now at 23 months of follow-up,” he said.
End of the line for HIPEC?
Invited discussant Elin. R. Sigurdson, MD, PhD, a professor in the department of surgical oncology at the Fox Chase Cancer Center, Philadelphia, framed her discussion by drawing on the words of emeritus surgeon Blake Cady, MD. “ ‘In the world of surgical oncology, biology is the King, selection of cases is Queen, and the technical aspects of the surgical procedures are the Princes and Princesses who frequently try to overthrow the King and the Queen.’ ”
Staging systems, such as the Peritoneal Carcinomatosis Index, have improved patient selection. “It’s obviously very critical to assess these patients appropriately at the time of surgery, and that has influenced this study,” she maintained. “The very early recurrences I think fall into the lap of the surgeons.”
Trials in established disease have helped sort out the roles of tumor debulking and HIPEC. “In our attempt to overcome the biology of this disease, we can see that, in most of these studies, the debulking-only arm did much better than we would have thought. But controversies remain regarding both the duration of the HIPEC and the chemotherapy that we use,” Dr. Sigurdson commented. “Perhaps, as we move forward, more questions will be addressed in the near future as there are ongoing clinical trials both on our side and the European side.”
Symposium attendee Alan P. Venook, MD, of the University of California, San Francisco, noted that there have been three negative clinical trials of HIPEC in the last 3 years. “Is that enough to say enough, or do we still need to study the role of HIPEC in these patients?” he asked.
“The issue becomes, are there new possibilities in the way of new drugs in order to carry on?” Dr. Sigurdson replied. Also, “it clearly has been a learning curve in doing HIPEC, and we have failed to recognize how impactful the surgical part of HIPEC has been.”
“The trials shown today from Europe are the best-designed trials that we have, and I agree, yes, the negative trials are discouraging,” she elaborated. “But if there were drugs where the therapeutic index of giving them intraperitoneally would be beneficial, then it would be useful because it has worked in ovarian cancer, it has worked in other cancers. So hope remains. But I would argue that, in the absence of new drugs, we are getting to the point that repeating the clinical trials with those [same] drugs is not going to be positive.”
Study details
In COLOPEC, adjuvant HIPEC consisted of 30 minutes of intraperitoneal oxaliplatin plus intravenous 5-fluoruracil and leucovorin, Dr. Tanis reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
HIPEC was usually performed 5-8 weeks after resection (91%) and laparoscopically (71%). Almost a fifth of patients were found to have extensive adhesions, making the procedure more difficult.
The rate of postoperative complications was 88% in the small number of patients having HIPEC at the time of resection, but only 6% in those having it 5-8 weeks after resection. A single patient developed encapsulating peritoneal sclerosis 8 months after HIPEC, requiring parenteral nutrition and surgery.
Patients in the HIPEC and control groups were similarly likely to receive adjuvant systemic chemotherapy (84% vs. 89%, P = .385), but the former had a longer time before starting this therapy (10.2 vs. 6.4 weeks, P less than .001).
Relative to counterparts in the control group, patients in the HIPEC group had a 14% reduction in risk of peritoneal recurrence or death at 18 months, but the difference was not significant (hazard ratio, 0.86; 95% confidence interval, 0.51-1.54). Findings were similar across a variety of subgroups.
In both trial groups, about two-thirds of patients in whom peritoneal metastases were detected underwent cytoreductive surgery and/or (additional) HIPEC to treat them.
“Overall, 21% of patients had peritoneal metastases detected after 23 months of follow-up, demonstrating the magnitude of this clinical problem,” noted Dr. Tanis, who reported that he had no relevant disclosures. The trial was sponsored by the Academic Medical Center, University of Amsterdam.
SOURCE: Tanis PJ et al. GI Cancers Symposium 2019, Abstract 482.
SAN FRANCISCO – according to primary results of the Dutch COLOPEC trial presented at the 2019 GI Cancers Symposium.
“Despite adjuvant systemic chemotherapy, locally advanced stage II and stage III colon cancer can give rise to metachronous peritoneal metastases in up to 25% of patients,” commented principal investigator Pieter J. Tanis, MD, PhD, a colorectal surgeon at the Academic Medical Center in Amsterdam. “These metastases are very difficult to detect, and when you detect them, they are difficult to treat.”
The 202 patients in COLOPEC, a multicenter, phase 3, randomized, controlled trial, underwent curative resection of primary colon tumors that were large (pT4 or cT4) or perforated, putting them at high risk for peritoneal metastases. All received routine adjuvant systemic chemotherapy.
At 18 months, the proportion of patients alive and free of peritoneal recurrence, assessed by laparoscopy, was 81% with addition of early postoperative oxaliplatin HIPEC and 76% without it, a nonsignificant difference.
“We couldn’t find any superiority of adjuvant HIPEC with oxaliplatin regarding peritoneal metastases–free survival in patients with T4 or perforated colon cancer,” Dr. Tanis summarized.
“We had a problem with the intention-to-treat analysis because 9% of patients already had recurrences before we performed the adjuvant HIPEC,” he added. “But I think we cannot perform an as-treated analysis in this trial because we don’t know the early recurrences in the control group.”
A symposium attendee wondered if the longer time to receiving systemic adjuvant systemic chemotherapy in the HIPEC group, a delay of about 4 weeks relative to the no-HIPEC group, was problematic and warranted consideration of neoadjuvant chemotherapy instead.
“The problem of the delay in chemotherapy, if you look in the literature, is there is no randomized trial looking at, for example, an 8- versus 12-week interval,” Dr. Tanis replied, noting that, in studies, adjuvant chemotherapy has most commonly been delayed because of patient comorbidities or surgical complications. “But you have to look very carefully at the expectation of the direct association between delay of chemotherapy and an effect. We have already looked at the disease-free survival and overall survival [in COLOPEC] and have not seen any difference … now at 23 months of follow-up,” he said.
End of the line for HIPEC?
Invited discussant Elin. R. Sigurdson, MD, PhD, a professor in the department of surgical oncology at the Fox Chase Cancer Center, Philadelphia, framed her discussion by drawing on the words of emeritus surgeon Blake Cady, MD. “ ‘In the world of surgical oncology, biology is the King, selection of cases is Queen, and the technical aspects of the surgical procedures are the Princes and Princesses who frequently try to overthrow the King and the Queen.’ ”
Staging systems, such as the Peritoneal Carcinomatosis Index, have improved patient selection. “It’s obviously very critical to assess these patients appropriately at the time of surgery, and that has influenced this study,” she maintained. “The very early recurrences I think fall into the lap of the surgeons.”
Trials in established disease have helped sort out the roles of tumor debulking and HIPEC. “In our attempt to overcome the biology of this disease, we can see that, in most of these studies, the debulking-only arm did much better than we would have thought. But controversies remain regarding both the duration of the HIPEC and the chemotherapy that we use,” Dr. Sigurdson commented. “Perhaps, as we move forward, more questions will be addressed in the near future as there are ongoing clinical trials both on our side and the European side.”
Symposium attendee Alan P. Venook, MD, of the University of California, San Francisco, noted that there have been three negative clinical trials of HIPEC in the last 3 years. “Is that enough to say enough, or do we still need to study the role of HIPEC in these patients?” he asked.
“The issue becomes, are there new possibilities in the way of new drugs in order to carry on?” Dr. Sigurdson replied. Also, “it clearly has been a learning curve in doing HIPEC, and we have failed to recognize how impactful the surgical part of HIPEC has been.”
“The trials shown today from Europe are the best-designed trials that we have, and I agree, yes, the negative trials are discouraging,” she elaborated. “But if there were drugs where the therapeutic index of giving them intraperitoneally would be beneficial, then it would be useful because it has worked in ovarian cancer, it has worked in other cancers. So hope remains. But I would argue that, in the absence of new drugs, we are getting to the point that repeating the clinical trials with those [same] drugs is not going to be positive.”
Study details
In COLOPEC, adjuvant HIPEC consisted of 30 minutes of intraperitoneal oxaliplatin plus intravenous 5-fluoruracil and leucovorin, Dr. Tanis reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
HIPEC was usually performed 5-8 weeks after resection (91%) and laparoscopically (71%). Almost a fifth of patients were found to have extensive adhesions, making the procedure more difficult.
The rate of postoperative complications was 88% in the small number of patients having HIPEC at the time of resection, but only 6% in those having it 5-8 weeks after resection. A single patient developed encapsulating peritoneal sclerosis 8 months after HIPEC, requiring parenteral nutrition and surgery.
Patients in the HIPEC and control groups were similarly likely to receive adjuvant systemic chemotherapy (84% vs. 89%, P = .385), but the former had a longer time before starting this therapy (10.2 vs. 6.4 weeks, P less than .001).
Relative to counterparts in the control group, patients in the HIPEC group had a 14% reduction in risk of peritoneal recurrence or death at 18 months, but the difference was not significant (hazard ratio, 0.86; 95% confidence interval, 0.51-1.54). Findings were similar across a variety of subgroups.
In both trial groups, about two-thirds of patients in whom peritoneal metastases were detected underwent cytoreductive surgery and/or (additional) HIPEC to treat them.
“Overall, 21% of patients had peritoneal metastases detected after 23 months of follow-up, demonstrating the magnitude of this clinical problem,” noted Dr. Tanis, who reported that he had no relevant disclosures. The trial was sponsored by the Academic Medical Center, University of Amsterdam.
SOURCE: Tanis PJ et al. GI Cancers Symposium 2019, Abstract 482.
SAN FRANCISCO – according to primary results of the Dutch COLOPEC trial presented at the 2019 GI Cancers Symposium.
“Despite adjuvant systemic chemotherapy, locally advanced stage II and stage III colon cancer can give rise to metachronous peritoneal metastases in up to 25% of patients,” commented principal investigator Pieter J. Tanis, MD, PhD, a colorectal surgeon at the Academic Medical Center in Amsterdam. “These metastases are very difficult to detect, and when you detect them, they are difficult to treat.”
The 202 patients in COLOPEC, a multicenter, phase 3, randomized, controlled trial, underwent curative resection of primary colon tumors that were large (pT4 or cT4) or perforated, putting them at high risk for peritoneal metastases. All received routine adjuvant systemic chemotherapy.
At 18 months, the proportion of patients alive and free of peritoneal recurrence, assessed by laparoscopy, was 81% with addition of early postoperative oxaliplatin HIPEC and 76% without it, a nonsignificant difference.
“We couldn’t find any superiority of adjuvant HIPEC with oxaliplatin regarding peritoneal metastases–free survival in patients with T4 or perforated colon cancer,” Dr. Tanis summarized.
“We had a problem with the intention-to-treat analysis because 9% of patients already had recurrences before we performed the adjuvant HIPEC,” he added. “But I think we cannot perform an as-treated analysis in this trial because we don’t know the early recurrences in the control group.”
A symposium attendee wondered if the longer time to receiving systemic adjuvant systemic chemotherapy in the HIPEC group, a delay of about 4 weeks relative to the no-HIPEC group, was problematic and warranted consideration of neoadjuvant chemotherapy instead.
“The problem of the delay in chemotherapy, if you look in the literature, is there is no randomized trial looking at, for example, an 8- versus 12-week interval,” Dr. Tanis replied, noting that, in studies, adjuvant chemotherapy has most commonly been delayed because of patient comorbidities or surgical complications. “But you have to look very carefully at the expectation of the direct association between delay of chemotherapy and an effect. We have already looked at the disease-free survival and overall survival [in COLOPEC] and have not seen any difference … now at 23 months of follow-up,” he said.
End of the line for HIPEC?
Invited discussant Elin. R. Sigurdson, MD, PhD, a professor in the department of surgical oncology at the Fox Chase Cancer Center, Philadelphia, framed her discussion by drawing on the words of emeritus surgeon Blake Cady, MD. “ ‘In the world of surgical oncology, biology is the King, selection of cases is Queen, and the technical aspects of the surgical procedures are the Princes and Princesses who frequently try to overthrow the King and the Queen.’ ”
Staging systems, such as the Peritoneal Carcinomatosis Index, have improved patient selection. “It’s obviously very critical to assess these patients appropriately at the time of surgery, and that has influenced this study,” she maintained. “The very early recurrences I think fall into the lap of the surgeons.”
Trials in established disease have helped sort out the roles of tumor debulking and HIPEC. “In our attempt to overcome the biology of this disease, we can see that, in most of these studies, the debulking-only arm did much better than we would have thought. But controversies remain regarding both the duration of the HIPEC and the chemotherapy that we use,” Dr. Sigurdson commented. “Perhaps, as we move forward, more questions will be addressed in the near future as there are ongoing clinical trials both on our side and the European side.”
Symposium attendee Alan P. Venook, MD, of the University of California, San Francisco, noted that there have been three negative clinical trials of HIPEC in the last 3 years. “Is that enough to say enough, or do we still need to study the role of HIPEC in these patients?” he asked.
“The issue becomes, are there new possibilities in the way of new drugs in order to carry on?” Dr. Sigurdson replied. Also, “it clearly has been a learning curve in doing HIPEC, and we have failed to recognize how impactful the surgical part of HIPEC has been.”
“The trials shown today from Europe are the best-designed trials that we have, and I agree, yes, the negative trials are discouraging,” she elaborated. “But if there were drugs where the therapeutic index of giving them intraperitoneally would be beneficial, then it would be useful because it has worked in ovarian cancer, it has worked in other cancers. So hope remains. But I would argue that, in the absence of new drugs, we are getting to the point that repeating the clinical trials with those [same] drugs is not going to be positive.”
Study details
In COLOPEC, adjuvant HIPEC consisted of 30 minutes of intraperitoneal oxaliplatin plus intravenous 5-fluoruracil and leucovorin, Dr. Tanis reported at the symposium, which is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
HIPEC was usually performed 5-8 weeks after resection (91%) and laparoscopically (71%). Almost a fifth of patients were found to have extensive adhesions, making the procedure more difficult.
The rate of postoperative complications was 88% in the small number of patients having HIPEC at the time of resection, but only 6% in those having it 5-8 weeks after resection. A single patient developed encapsulating peritoneal sclerosis 8 months after HIPEC, requiring parenteral nutrition and surgery.
Patients in the HIPEC and control groups were similarly likely to receive adjuvant systemic chemotherapy (84% vs. 89%, P = .385), but the former had a longer time before starting this therapy (10.2 vs. 6.4 weeks, P less than .001).
Relative to counterparts in the control group, patients in the HIPEC group had a 14% reduction in risk of peritoneal recurrence or death at 18 months, but the difference was not significant (hazard ratio, 0.86; 95% confidence interval, 0.51-1.54). Findings were similar across a variety of subgroups.
In both trial groups, about two-thirds of patients in whom peritoneal metastases were detected underwent cytoreductive surgery and/or (additional) HIPEC to treat them.
“Overall, 21% of patients had peritoneal metastases detected after 23 months of follow-up, demonstrating the magnitude of this clinical problem,” noted Dr. Tanis, who reported that he had no relevant disclosures. The trial was sponsored by the Academic Medical Center, University of Amsterdam.
SOURCE: Tanis PJ et al. GI Cancers Symposium 2019, Abstract 482.
REPORTING FROM THE 2019 GI CANCERS SYMPOSIUM
Key clinical point: Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) is not efficacious in patients undergoing curative resection of high-risk colon cancer.
Major finding: The rate of peritoneal metastasis–free survival at 18 months was 81% with HIPEC and 76% without HIPEC (hazard ratio, 0.86; 95% confidence interval, 0.51-1.54).
Study details: A phase 3, randomized, controlled trial among 202 patients who underwent curative resection of colon cancer having stage T4 or perforated tumors, all given adjuvant systemic chemotherapy (COLOPEC).
Disclosures: Dr. Tanis reported no relevant relationships. The trial was sponsored by the Academic Medical Center, University of Amsterdam.
Source: Tanis PJ et al. GI Cancers Symposium 2019, Abstract 482.
Young women opt for mastectomy even when neoadjuvant chemo works well
SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.
Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.
“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”
The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.
“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”
The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.
Drivers and explanatory factors
Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”
“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”
Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.
“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”
The study did not tease out that population, Dr. Kim replied.
Study details
The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).
Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.
However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.
Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.
Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.
The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.
In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.
SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.
Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.
“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”
The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.
“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”
The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.
Drivers and explanatory factors
Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”
“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”
Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.
“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”
The study did not tease out that population, Dr. Kim replied.
Study details
The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).
Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.
However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.
Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.
Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.
The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.
In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.
SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
SAN ANTONIO – Response to neoadjuvant chemotherapy has little if any influence on the choice of surgery among young women with early-stage breast cancer, suggests a multicenter, prospective cohort study reported at the San Antonio Breast Cancer Symposium.
Randomized, controlled trials have found high levels of mastectomy among patients who are eligible for breast-conserving surgery, according to first author Hee Jeong Kim, MD, PhD, a visiting scholar at the Dana-Farber Cancer Institute, Boston, and an associate professor in the division of breast in the department of surgery at the University of Ulsan, Seoul, South Korea.
“Young women are more likely to present with large tumors and particularly benefit from a neoadjuvant systemic approach,” she noted. “Recent data suggest that response rates, including pathological complete response, are higher in women younger than 40 than in older women, but little is known about how response to neoadjuvant chemotherapy influences surgical decisions in young women.”
The investigators studied 315 women aged 40 years or younger at diagnosis of unilateral stage I-III breast cancer who received neoadjuvant chemotherapy. Results showed that the chemotherapy doubled the proportion who were eligible for breast-conserving surgery, but 41% of all women eligible after neoadjuvant chemotherapy opted to undergo mastectomy, and the value was essentially the same (42%) among the subset who achieved a complete clinical response. The leading reason given in the medical record for this choice was personal preference in the absence of any known high-risk predisposition.
“Surgical decisions among young women with breast cancer appear to be driven by factors beyond the extent of disease and response to neoadjuvant chemotherapy,” she commented. “We should focus our efforts to optimize surgical decisions in these patients.”
The study complements another study undertaken in the same cohort, also reported at the symposium, that assessed longer-term quality of life according to which surgery women chose; this quality-of-life study found poorer measures after mastectomy.
Drivers and explanatory factors
Session moderator Fatima Cardoso, MD, director of the Breast Unit at the Champalimaud Clinical Center in Lisbon, asked, “Do you think this is really the patient preference, or is this more the surgeon’s preference that is passed on to the patient? Because there is now data showing that breast conservation with radiation is better, even in terms of survival, than mastectomy.”
“Patient preference includes a variety of things. Maybe it is a real patient preference [driven by] fear of recurrence or their peace of mind, but another important factor is maybe the doctor, especially the surgeon. That’s why we should be aware of surgical overtreatment, especially in these young early breast cancer patients,” Dr. Kim replied. “But the good news from this study is that neoadjuvant chemotherapy can give options to the patients, they can choose mastectomy. I think that it’s totally different when the patient has no option other than mastectomy versus the patient can choose mastectomy.”
Two main groups of patients in the United States are being given neoadjuvant chemotherapy, noted session attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York. One group has large tumors, and the goal is to shrink the tumor; the other group is planning to have unilateral or bilateral mastectomy with some type of reconstruction by a plastic surgeon.
“The medical oncologist, having decided the [latter] patient needs chemotherapy, chooses to give the chemotherapy preoperatively, so it’s not delayed by 3-5 months for the wounds to heal,” he elaborated. “How many of your patients were in the second category?”
The study did not tease out that population, Dr. Kim replied.
Study details
The women studied were participants in the Young Women’s Breast Cancer Study (YWS). Some 67% had a clinical complete response (no palpable tumor in the breast) to their neoadjuvant chemotherapy, and 32% had a pathological complete response (no tumor in the breast, with or without ductal carcinoma in situ [DCIS], and no tumor deposit exceeding 0.2 mm in the lymph nodes).
Before neoadjuvant chemotherapy, 26% of the women overall were eligible for breast-conserving surgery, but after neoadjuvant chemotherapy, 42% were eligible, Dr. Kim reported.
However, in the entire cohort, breast-conserving surgery was the initial surgery in just 25% of women and the final (definitive) surgery in just 23%.
Among patients eligible for breast conservation after neoadjuvant chemotherapy, 41% chose mastectomy instead as their initial surgery. Response to the chemotherapy seemingly did not influence this choice given that 42% of the subset with a clinical complete response still chose mastectomy. Furthermore, among those eligible for breast conservation who underwent mastectomy, 35% had a pathologic complete response to the chemotherapy.
Of all patients eligible for breast-conserving surgery who opted for mastectomy (and usually a bilateral procedure), the most common reason for choosing this more extensive surgery was personal preference, documented in 53% of cases, followed by presence of a BRCA or p53 mutation or a strong family history, documented in 40%. Reasons were similar among the breast conservation–eligible women who had a clinical complete response and/or ultimately a pathological complete response but chose mastectomy.
The study did not analyze disease factors that may have influenced choice of surgery, such as multicentricity or presence of DCIS, acknowledged Dr. Kim, who disclosed that she had no relevant conflicts of interest.
In an exploratory analysis, use of neoadjuvant chemotherapy increased over time among YWS participants, from 23% among those with diagnosis in 2006-2007 to 44% among those with diagnosis in 2014-2015. There were concurrent improvements in the proportions who achieved a clinical complete response (from 64% to 77%) and a pathological complete response (from 23% to 34%). Yet the proportion undergoing breast-conserving surgery as their initial surgery fell slightly, from 21% to 19%, during the same period.
SOURCE: Kim HJ et al. SABCS 2018, Abstract GS6-01,
REPORTING FROM SABCS 2018
Key clinical point: Response to neoadjuvant chemotherapy does not alter choice of surgery among young breast cancer patients.
Major finding: Neoadjuvant chemotherapy increased the proportion eligible for breast-conserving surgery from 26% to 42%, but about 40% of those eligible chose mastectomy regardless of chemotherapy response, mainly because of personal preference.
Study details: A multicenter, prospective cohort study of 315 women aged 40 years or younger at diagnosis of early-stage breast cancer who received neoadjuvant chemotherapy (Young Women’s Breast Cancer Study).
Disclosures: Dr. Kim disclosed that she had no relevant conflicts of interest.
Source: Kim HJ et al. SABCS 2018, Abstract GS6-01.
Older breast cancer patients given adjuvant chemo live longer
SAN ANTONIO – captured in the National Cancer Database.
“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.
In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.
Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.
“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.
In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.
“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.
He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”
“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”
Study details
The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.
Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.
Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).
Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).
Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.
The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).
“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted
Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.
SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.
SAN ANTONIO – captured in the National Cancer Database.
“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.
In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.
Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.
“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.
In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.
“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.
He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”
“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”
Study details
The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.
Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.
Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).
Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).
Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.
The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).
“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted
Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.
SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.
SAN ANTONIO – captured in the National Cancer Database.
“Data for elderly patients in clinical trials is limited. The NCCN [National Comprehensive Cancer Network] guidelines note that there is limited data to make chemotherapy recommendations for those older than 70 years of age,” commented first author Shreya Sinha, MD, an oncology fellow at the State University of New York, Syracuse. Furthermore, the few studies assessing adjuvant chemotherapy benefit among geriatric breast cancer patients have had conflicting results.
In the new study, reported at the San Antonio Breast Cancer Symposium, older women with stage I-III breast cancer who received adjuvant chemotherapy had a nearly 40% reduction in the adjusted risk of death relative to counterparts who did not receive adjuvant chemotherapy. Benefit was seen across disease stages and across hormone receptor statuses.
Patients’ fitness to receive chemotherapy and their causes of death could not be determined, Dr. Sinha acknowledged. Therefore, chemotherapy’s role in the observed survival difference is not definitive.
“In general, when we are treating our elderly population, we have to take physiologic age into consideration when coming up with a treatment plan,” she said. However, “we also have to use chemotherapy toxicity prediction calculators,” such as the Cancer and Aging Research Group tool and the Chemotherapy Risk Assessment Scale for High-Age Patients.
In addition, gene-based assays, such as Oncotype DX and MammaPrint, which were not taken into account for the study, can be applied to estimate the likely benefit of chemotherapy and further inform the treatment decision.
“It can’t be that chemotherapy is making these patients live longer. It has to be that the doctors know not to give chemotherapy to those who are going to die soon,” speculated symposium attendee Steven E. Vogl, MD, an oncologist at Montefiore Medical Center, New York.
He therefore wondered if the amount of chemotherapy received was related to survival. “If it was a chemotherapy effect, then more is probably better, and if it’s a selection effect at the time of initiation, then more probably wouldn’t be better.”
“These are the issues we run into when we use the National Cancer Database or such large databases,” Dr. Sinha replied. “We don’t necessarily have the information on how much chemotherapy the patients received. It really is based on if they received chemotherapy or not.”
Study details
The 160,676 patients studied were treated for stage I-III breast cancer during 2004-2015 and were included regardless of hormone receptor status and HER2 status.
Overall, 60.45% received adjuvant chemotherapy, Dr. Sinha reported. Mean age was 70.7 years among chemotherapy recipients and 75.5 years among nonrecipients.
Women were more likely to receive adjuvant chemotherapy if they had a tumor grade of 2 or 3 (adjusted odds ratios, 1.88 and 3.51), had a tumor negative for both estrogen and progesterone receptors or just progesterone receptors (aOR, 2.72 and 1.70), had private insurance versus Medicaid or Medicare (aOR, 1.40 and 1.20), or received radiation therapy (aOR, 2.55).
Women were less likely to receive adjuvant chemotherapy if they had stage 1 or 2 disease (aOR, 0.23 and 0.56; P less than .0001 for each), were older than 80 years (aOR, 0.105; P less than .0001), had undergone lumpectomy versus mastectomy (aOR, 0.82; P = .0011), were treated in an academic versus community program (aOR, 0.93; P = .0007), or had a Charlson/Deyo comorbidity score of 3 or higher (aOR, 0.38; P less than .0001).
Median overall survival was 144.9 months with and 112.6 months without adjuvant chemotherapy. The difference translated to a significantly reduced risk of death for the women given adjuvant chemotherapy (adjusted hazard ratio, 0.617; P less than .0001). The corresponding 10-year overall survival rates were 59.5% and 46.7%.
The reduced risk of death with adjuvant chemotherapy was evident in women with stage 1 disease (aHR, 0.801), stage 2 disease (aHR, 0.608), and stage 3 disease (aHR, 0.666) (P less than .0001 for all). It was also evident in those with tumors positive for both estrogen and progesterone receptors (aHR, 0.649), negative for progesterone receptors only (aHR, 0.609), and negative for both (aHR, 0.547) (P less than .0001 for all).
“The HER2/neu patient unfortunately was not well defined since there was no data [on that marker] before 2010,” Dr. Sinha noted
Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.
SOURCE: Sinha S et al. SABCS 2018, Abstract GS2-02.
REPORTING FROM SABCS 2018
Key clinical point: Older patients with early breast cancer who are given adjuvant chemotherapy live longer.
Major finding: Receipt of adjuvant chemotherapy was associated with a reduced risk of death after taking into account factors such as age and comorbidity burden (adjusted hazard ratio, 0.617; P less than .0001).
Study details: A retrospective cohort study of 160,676 breast cancer patients aged 65 years and older with stage I-III disease.
Disclosures: Dr. Sinha reported no relevant conflicts of interest. The study received funding from the Research Foundation of SUNY.
Source: Sinha S et al. SABCS 2018, Abstract GS2-02.
QOL is poorer for young women after mastectomy than BCS
SAN ANTONIO – , according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.
Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.
“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”
Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.
“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
Moving away from mastectomy
“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.
“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”
The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
Study details
The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)
Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).
Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).
Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).
The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.
Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.
“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”
Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.
SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,
SAN ANTONIO – , according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.
Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.
“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”
Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.
“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
Moving away from mastectomy
“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.
“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”
The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
Study details
The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)
Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).
Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).
Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).
The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.
Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.
“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”
Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.
SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,
SAN ANTONIO – , according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.
Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.
“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”
Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.
“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
Moving away from mastectomy
“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.
“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”
The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
Study details
The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)
Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).
Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).
Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).
The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.
Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.
“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”
Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.
SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,
REPORTING FROM SABCS 2018
Key clinical point: More extensive breast surgery has a long-term negative impact on QOL for young breast cancer survivors.
Major finding: Compared with peers who underwent breast-conserving surgery, young women who underwent unilateral or bilateral mastectomy had significantly poorer adjusted scores for breast satisfaction (beta, –8.7 and –9.3 points) and psychosocial well-being (beta, –8.3 and –10.5 points).
Study details: A multicenter cross-sectional cohort study of 560 women with a mean age of 37 years at breast cancer diagnosis who completed the BREAST-Q questionnaire a median of 5.8 years later.
Disclosures: Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.
Source: Dominici LS et al. SABCS 2018, Abstract GS6-06.
Oxybutynin rapidly quells hot flashes
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
SAN ANTONIO – because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.
Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium
But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.
The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.
The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.
Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.
“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
Treatment considerations
“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.
“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.
His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”
As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.
It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.
“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
Study details
The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.
In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.
Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.
Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.
Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.
REPORTING FROM SABCS 2018
Partial- and whole-breast irradiation very close in efficacy
SAN ANTONIO – , suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.
At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.
Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.
“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
Implications for practice and research
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.
“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”
Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”
It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.
The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
Study details
Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).
The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).
The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).
Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,
SAN ANTONIO – , suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.
At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.
Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.
“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
Implications for practice and research
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.
“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”
Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”
It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.
The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
Study details
Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).
The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).
The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).
Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,
SAN ANTONIO – , suggests a phase 3, randomized, controlled trial conducted by NRG Oncology.
At a median follow-up of 10.2 years, the trial was unable to refute the hypothesis that the partial technique was inferior in terms of ipsilateral breast tumor recurrences; however, the difference between techniques in this outcome was an absolute 0.7%, lead investigator Frank Vicini, MD, principal investigator at the MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Mich., reported in a session and press conference at the San Antonio Breast Cancer Symposium. The difference in recurrence-free interval was significant but likewise small, at 1.6%, and other efficacy outcomes were similar.
Meanwhile, the groups had low, statistically indistinguishable rates of grade 3-5 toxicities and second cancers. The investigators are still analyzing quality of life and cosmesis outcomes.
“This was the largest trial ever looking at partial-breast [irradiation] in a very diverse group of patients. Even though we weren’t able to demonstrate equivalence, it’s nice to see that in this large population of patients with extended follow-up, the differences are quite small,” Dr. Vicini said. “Because the differences for both ipsilateral breast tumor recurrence and recurrence-free interval were very small, partial-breast irradiation may be an acceptable alternative to whole-breast irradiation for a proportion of women who are undergoing breast-conserving surgery.”
Implications for practice and research
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at UT Health San Antonio, asked how the findings have influenced his practice.
“This trial is over 15 years old now, and a lot of these techniques have been refined. But we are offering partial-breast irradiation to our patients,” Dr. Vicini replied. “There are a lot of competing ways to do radiation now; probably the biggest competing way is to do 3 weeks of whole-breast irradiation. But for those patients who have transportation issues and more elderly patients, we try to offer partial-breast irradiation, within the guidelines of ASTRO [American Society for Therapeutic Radiology and Oncology].”
Some of the women enrolled had risk factors that fall outside those guidelines, for example, higher-grade tumors or axillary node involvement, he acknowledged. “We tried to do exploratory analyses to look at whether certain patients did better with whole-breast irradiation or not, and we weren’t able to really pick out any group of patients that had better or worse outcome based on those criteria,” he said. “We have yet to look at the quality indices for radiation therapy, in other words, how much the breast actually needs to be treated. But at the present time, I would just suggest sticking with the ASTRO guidelines.”
It is noteworthy that likely the most important endpoints, disease-free and overall survival, did not differ between groups, according to Dr. Vicini. “Certainly, a recurrence is still an important event for a patient, so our goal is to always limit that as much as possible,” he said. “But putting it into perspective, does a 0.7% higher risk of recurrence [matter] when you know the survival rates are the same? That’s what patients and doctors need to take into consideration. This is a pretty dramatic difference in treatment [duration], 6 weeks, down to 1 week or less. There have been many studies looking at quality of life and, as you can imagine, quality of life is better” with the shorter therapy.
The trial’s results can also inform statistical planning of future trials, according to Dr. Kaklamani. “It’s important when we design the trials to look at clinically meaningful differences because we don’t want to harm our patients, but at the same time, we are also harming them by giving them more treatment. So if you are designing a trial where a 0.7% difference is statistically significant, you probably would have been able to get away with many fewer patients and a difference of 1.5% or 2% not being significant, and I think everybody would be happy with that.”
Study details
Dr. Vicini and colleagues enrolled in their trial 4,216 women with stage 0-II breast cancer who had undergone lumpectomy. They were randomized to whole-breast irradiation (5-6 weeks of radiation therapy at that time) or partial-breast irradiation using one of three techniques (3D conformal external beam radiation completed in 5 days, interstitial brachytherapy completed in 5 days, or device-based brachytherapy).
The hazard ratio for ipsilateral breast tumor recurrence (invasive or DCIS) as a first recurrence with partial-breast irradiation versus whole-breast irradiation was 1.22, with the upper bound of the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5), Dr. Vicini reported. However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was merely 0.7% (4.6% vs. 3.9%).
The 10-year recurrence-free interval was inferior with partial-breast irradiation (hazard ratio, 1.33; P = .02), but the absolute difference was again small at 1.6% (91.8% vs 93.4%). The partial- and whole-breast irradiation groups were statistically indistinguishable on distant disease-free interval (96.7% vs 97.1%; HR, 1.31; P = .15) and overall survival (90.6% vs. 91.3%; HR, 1.10; P = .35).
Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
SOURCE: Vicini FA et al. SABCS 2018, Abstract GS4-04,
REPORTING FROM SABCS 2018
Key clinical point: Partial- and whole-breast irradiation yield outcomes that are statistically nonequivalent but very similar.
Major finding: The hazard ratio for ipsilateral recurrences with partial- vs. whole-breast irradiation was 1.22, with the confidence interval falling just outside the range for equivalence, but the absolute difference in 10-year rate was just 0.7% (4.6% vs. 3.9%).
Study details: A phase 3, randomized, controlled trial among women who underwent lumpectomy for stage 0-II breast cancer, conducted by NRG Oncology (NSABP B-39/RTOG 0413).
Disclosures: Dr. Vicini disclosed that he is a research advisor for ImpediMed. The study was sponsored by the National Cancer Institute.
Source: Vicini FA et al. SABCS 2018, Abstract GS4-04.
AMAROS: Radiation has edge for axillary treatment
SAN ANTONIO – For treatment of the axilla in women with early-stage breast cancer having a positive sentinel node, the risk-benefit calculus tilts toward radiation therapy over axillary lymph node dissection, finds an update of the phase 3, noninferiority, randomized AMAROS trial.
The trial’s previously reported 5-year results showed noninferiority of axillary radiation relative to axillary lymph node dissection (ALND) with respect to axillary recurrences, as well as less lymphedema (Lancet Oncol. 2014 Nov;15(12):1303-10). But the trial was criticized as being underpowered and having insufficient follow-up, according to principal investigator Emiel J. T. Rutgers, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.
Now, at a median follow-up of 10 years, findings were basically the same, with few additional axillary recurrences having occurred in either group, he reported in a session and press conference at the San Antonio Breast Cancer Symposium. There was a nonsignificant difference in the very-low 10-year cumulative incidences of axillary recurrence, and no significant difference in other efficacy outcomes. Meanwhile, an update of the rate of lymphedema at 5 years continued to show that this treatment complication was about half as common with radiation.
The radiation therapy group did have a higher risk of second primaries, with an absolute difference of about 4%, mainly driven by more contralateral breast cancers. But it was unclear whether this difference was related to the radiation, according to Dr. Rutgers.
“Both axillary clearance and radiotherapy provide excellent, comparable locoregional control in patients who have a positive sentinel node in the axilla,” he summarized. “After 10 years [of follow-up], there is significantly less lymphedema after radiation therapy at 5 years, and therefore this can be considered a standard procedure.”
Putting data into practice
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at University of Texas, San Antonio, wondered how Dr. Rutger’s institution has incorporated findings of the AMAROS trial and findings of the previously reported ACOSOG Z11 trial (JAMA. 2011;305:569-75).
They apply both, on a case-by-case basis, he replied. “If it’s limited node involvement in early breast cancer – and of course that’s subjective, we have some cutoffs for that – we do nothing if the sentinel node is positive. If it’s a larger tumor, high grade, lymphovascular invasion, and there are two positive sentinel nodes, then we irradiate the axilla according to the AMAROS trial. This is a discussion within our tumor board, of course, with the multidisciplinary team and together with the patient.”
Over the past 20 years, the percentage of women at his institute undergoing axillary clearance has fallen sharply, from about 75% to merely 3%, as a result of introduction of and growing evidence on sentinel node biopsy, advances in radiation therapy, and increased use of neoadjuvant chemotherapy, according to Dr. Rutgers. “At our institute, an axillary clearance in breast cancer is a rare operation for our residents. They have to go to the melanoma doctors to learn axillary clearance.” At the same time, the occurrence of lymph node metastases has remained unchanged at about 1% annually.
“This is really the beauty of this sort of deescalation in therapy, where you’re improving the morbidity of our patients – our patients have a better quality of life because they don’t have as much lymphedema – without compromising their outcomes. The chance of them having a local recurrence is very low,” Dr. Kaklamani commented. “So taking 20 and 30 and sometimes 40 lymph nodes out, like we used to do, isn’t needed anymore.”
Still, selecting the right patient for radiation is important, she cautioned, as the findings do not apply to those with a bulky lymph node, for example. “But the majority of patients we see with breast cancer have these small metastases to their axillas, if they do [have any], and in those cases, doing radiation, instead of doing more surgery or not doing anything, is very appropriate.”
Changing the standard in the United States has historically been slow. “It is the longer follow-ups from Z11, from AMAROS that are helping our surgeons cut back on the amount of surgery that they are doing,” Dr. Kaklamani maintained. “I have been surprised because we have had these trials out for 10 years, and we still are doing more axillary node dissections than we should be doing.”
At the global level, trends in use of ALND by country and region have varied depending on national practice patterns and acceptance of the trial data, according to Dr. Rutgers. “Taking a toy away from a surgeon is a difficult thing to do.”
Study details
The AMAROS trial was conducted by the European Organization for Research and Treatment of Cancer Breast Cancer Group and Radiation Oncology Group, in collaboration with the Dutch Breast Cancer Research Group and the ALMANAC Trialists’ Group.
The 1,425 patients randomized had breast cancer that was clinically node negative by either palpation or ultrasound (cT1-2,N0) and were scheduled for breast-conserving surgery or mastectomy.
The updated results showed that the 10-year cumulative incidence of axillary recurrence was 1.82% with axillary radiation and 0.93% with ALND, a nonsignificant difference (hazard ratio, 1.71; P = .365), Dr. Rutgers reported. The women also had statistically indistinguishable rates of disease-free survival (HR, 1.19; P = .105), as well as distant metastasis–free survival and overall survival.
The 10-year cumulative incidence of second primaries was higher with radiation than with ALND: 12.09% versus 8.33% (HR, 1.45; P = .035). “This is to some extent due to contralateral breast cancers,” Dr. Rutgers commented. “We cannot exclude an effect of the radiotherapy to the axilla, but we have to realize that 85% of these patients received radiotherapy anyway because of breast conservation. So for us, it is difficult to see whether the addition of the axillary radiation field would lead to more second primaries.”
The updated 5-year rate of lymphedema (data for this outcome were not collected at 10 years) showed persistence of a large difference in the occurrence of lymphedema as defined by clinical observation and/or treatment: 29.4% with ALND and 14.6% with radiation (P less than .0001).
Dr. Rutgers reported that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.
SOURCE: Rutgers EJT et al. SABCS 2018, Abstract GS4-01.
SAN ANTONIO – For treatment of the axilla in women with early-stage breast cancer having a positive sentinel node, the risk-benefit calculus tilts toward radiation therapy over axillary lymph node dissection, finds an update of the phase 3, noninferiority, randomized AMAROS trial.
The trial’s previously reported 5-year results showed noninferiority of axillary radiation relative to axillary lymph node dissection (ALND) with respect to axillary recurrences, as well as less lymphedema (Lancet Oncol. 2014 Nov;15(12):1303-10). But the trial was criticized as being underpowered and having insufficient follow-up, according to principal investigator Emiel J. T. Rutgers, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.
Now, at a median follow-up of 10 years, findings were basically the same, with few additional axillary recurrences having occurred in either group, he reported in a session and press conference at the San Antonio Breast Cancer Symposium. There was a nonsignificant difference in the very-low 10-year cumulative incidences of axillary recurrence, and no significant difference in other efficacy outcomes. Meanwhile, an update of the rate of lymphedema at 5 years continued to show that this treatment complication was about half as common with radiation.
The radiation therapy group did have a higher risk of second primaries, with an absolute difference of about 4%, mainly driven by more contralateral breast cancers. But it was unclear whether this difference was related to the radiation, according to Dr. Rutgers.
“Both axillary clearance and radiotherapy provide excellent, comparable locoregional control in patients who have a positive sentinel node in the axilla,” he summarized. “After 10 years [of follow-up], there is significantly less lymphedema after radiation therapy at 5 years, and therefore this can be considered a standard procedure.”
Putting data into practice
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at University of Texas, San Antonio, wondered how Dr. Rutger’s institution has incorporated findings of the AMAROS trial and findings of the previously reported ACOSOG Z11 trial (JAMA. 2011;305:569-75).
They apply both, on a case-by-case basis, he replied. “If it’s limited node involvement in early breast cancer – and of course that’s subjective, we have some cutoffs for that – we do nothing if the sentinel node is positive. If it’s a larger tumor, high grade, lymphovascular invasion, and there are two positive sentinel nodes, then we irradiate the axilla according to the AMAROS trial. This is a discussion within our tumor board, of course, with the multidisciplinary team and together with the patient.”
Over the past 20 years, the percentage of women at his institute undergoing axillary clearance has fallen sharply, from about 75% to merely 3%, as a result of introduction of and growing evidence on sentinel node biopsy, advances in radiation therapy, and increased use of neoadjuvant chemotherapy, according to Dr. Rutgers. “At our institute, an axillary clearance in breast cancer is a rare operation for our residents. They have to go to the melanoma doctors to learn axillary clearance.” At the same time, the occurrence of lymph node metastases has remained unchanged at about 1% annually.
“This is really the beauty of this sort of deescalation in therapy, where you’re improving the morbidity of our patients – our patients have a better quality of life because they don’t have as much lymphedema – without compromising their outcomes. The chance of them having a local recurrence is very low,” Dr. Kaklamani commented. “So taking 20 and 30 and sometimes 40 lymph nodes out, like we used to do, isn’t needed anymore.”
Still, selecting the right patient for radiation is important, she cautioned, as the findings do not apply to those with a bulky lymph node, for example. “But the majority of patients we see with breast cancer have these small metastases to their axillas, if they do [have any], and in those cases, doing radiation, instead of doing more surgery or not doing anything, is very appropriate.”
Changing the standard in the United States has historically been slow. “It is the longer follow-ups from Z11, from AMAROS that are helping our surgeons cut back on the amount of surgery that they are doing,” Dr. Kaklamani maintained. “I have been surprised because we have had these trials out for 10 years, and we still are doing more axillary node dissections than we should be doing.”
At the global level, trends in use of ALND by country and region have varied depending on national practice patterns and acceptance of the trial data, according to Dr. Rutgers. “Taking a toy away from a surgeon is a difficult thing to do.”
Study details
The AMAROS trial was conducted by the European Organization for Research and Treatment of Cancer Breast Cancer Group and Radiation Oncology Group, in collaboration with the Dutch Breast Cancer Research Group and the ALMANAC Trialists’ Group.
The 1,425 patients randomized had breast cancer that was clinically node negative by either palpation or ultrasound (cT1-2,N0) and were scheduled for breast-conserving surgery or mastectomy.
The updated results showed that the 10-year cumulative incidence of axillary recurrence was 1.82% with axillary radiation and 0.93% with ALND, a nonsignificant difference (hazard ratio, 1.71; P = .365), Dr. Rutgers reported. The women also had statistically indistinguishable rates of disease-free survival (HR, 1.19; P = .105), as well as distant metastasis–free survival and overall survival.
The 10-year cumulative incidence of second primaries was higher with radiation than with ALND: 12.09% versus 8.33% (HR, 1.45; P = .035). “This is to some extent due to contralateral breast cancers,” Dr. Rutgers commented. “We cannot exclude an effect of the radiotherapy to the axilla, but we have to realize that 85% of these patients received radiotherapy anyway because of breast conservation. So for us, it is difficult to see whether the addition of the axillary radiation field would lead to more second primaries.”
The updated 5-year rate of lymphedema (data for this outcome were not collected at 10 years) showed persistence of a large difference in the occurrence of lymphedema as defined by clinical observation and/or treatment: 29.4% with ALND and 14.6% with radiation (P less than .0001).
Dr. Rutgers reported that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.
SOURCE: Rutgers EJT et al. SABCS 2018, Abstract GS4-01.
SAN ANTONIO – For treatment of the axilla in women with early-stage breast cancer having a positive sentinel node, the risk-benefit calculus tilts toward radiation therapy over axillary lymph node dissection, finds an update of the phase 3, noninferiority, randomized AMAROS trial.
The trial’s previously reported 5-year results showed noninferiority of axillary radiation relative to axillary lymph node dissection (ALND) with respect to axillary recurrences, as well as less lymphedema (Lancet Oncol. 2014 Nov;15(12):1303-10). But the trial was criticized as being underpowered and having insufficient follow-up, according to principal investigator Emiel J. T. Rutgers, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.
Now, at a median follow-up of 10 years, findings were basically the same, with few additional axillary recurrences having occurred in either group, he reported in a session and press conference at the San Antonio Breast Cancer Symposium. There was a nonsignificant difference in the very-low 10-year cumulative incidences of axillary recurrence, and no significant difference in other efficacy outcomes. Meanwhile, an update of the rate of lymphedema at 5 years continued to show that this treatment complication was about half as common with radiation.
The radiation therapy group did have a higher risk of second primaries, with an absolute difference of about 4%, mainly driven by more contralateral breast cancers. But it was unclear whether this difference was related to the radiation, according to Dr. Rutgers.
“Both axillary clearance and radiotherapy provide excellent, comparable locoregional control in patients who have a positive sentinel node in the axilla,” he summarized. “After 10 years [of follow-up], there is significantly less lymphedema after radiation therapy at 5 years, and therefore this can be considered a standard procedure.”
Putting data into practice
SABCS codirector and press conference moderator Virginia Kaklamani, MD, leader of the breast cancer program at University of Texas, San Antonio, wondered how Dr. Rutger’s institution has incorporated findings of the AMAROS trial and findings of the previously reported ACOSOG Z11 trial (JAMA. 2011;305:569-75).
They apply both, on a case-by-case basis, he replied. “If it’s limited node involvement in early breast cancer – and of course that’s subjective, we have some cutoffs for that – we do nothing if the sentinel node is positive. If it’s a larger tumor, high grade, lymphovascular invasion, and there are two positive sentinel nodes, then we irradiate the axilla according to the AMAROS trial. This is a discussion within our tumor board, of course, with the multidisciplinary team and together with the patient.”
Over the past 20 years, the percentage of women at his institute undergoing axillary clearance has fallen sharply, from about 75% to merely 3%, as a result of introduction of and growing evidence on sentinel node biopsy, advances in radiation therapy, and increased use of neoadjuvant chemotherapy, according to Dr. Rutgers. “At our institute, an axillary clearance in breast cancer is a rare operation for our residents. They have to go to the melanoma doctors to learn axillary clearance.” At the same time, the occurrence of lymph node metastases has remained unchanged at about 1% annually.
“This is really the beauty of this sort of deescalation in therapy, where you’re improving the morbidity of our patients – our patients have a better quality of life because they don’t have as much lymphedema – without compromising their outcomes. The chance of them having a local recurrence is very low,” Dr. Kaklamani commented. “So taking 20 and 30 and sometimes 40 lymph nodes out, like we used to do, isn’t needed anymore.”
Still, selecting the right patient for radiation is important, she cautioned, as the findings do not apply to those with a bulky lymph node, for example. “But the majority of patients we see with breast cancer have these small metastases to their axillas, if they do [have any], and in those cases, doing radiation, instead of doing more surgery or not doing anything, is very appropriate.”
Changing the standard in the United States has historically been slow. “It is the longer follow-ups from Z11, from AMAROS that are helping our surgeons cut back on the amount of surgery that they are doing,” Dr. Kaklamani maintained. “I have been surprised because we have had these trials out for 10 years, and we still are doing more axillary node dissections than we should be doing.”
At the global level, trends in use of ALND by country and region have varied depending on national practice patterns and acceptance of the trial data, according to Dr. Rutgers. “Taking a toy away from a surgeon is a difficult thing to do.”
Study details
The AMAROS trial was conducted by the European Organization for Research and Treatment of Cancer Breast Cancer Group and Radiation Oncology Group, in collaboration with the Dutch Breast Cancer Research Group and the ALMANAC Trialists’ Group.
The 1,425 patients randomized had breast cancer that was clinically node negative by either palpation or ultrasound (cT1-2,N0) and were scheduled for breast-conserving surgery or mastectomy.
The updated results showed that the 10-year cumulative incidence of axillary recurrence was 1.82% with axillary radiation and 0.93% with ALND, a nonsignificant difference (hazard ratio, 1.71; P = .365), Dr. Rutgers reported. The women also had statistically indistinguishable rates of disease-free survival (HR, 1.19; P = .105), as well as distant metastasis–free survival and overall survival.
The 10-year cumulative incidence of second primaries was higher with radiation than with ALND: 12.09% versus 8.33% (HR, 1.45; P = .035). “This is to some extent due to contralateral breast cancers,” Dr. Rutgers commented. “We cannot exclude an effect of the radiotherapy to the axilla, but we have to realize that 85% of these patients received radiotherapy anyway because of breast conservation. So for us, it is difficult to see whether the addition of the axillary radiation field would lead to more second primaries.”
The updated 5-year rate of lymphedema (data for this outcome were not collected at 10 years) showed persistence of a large difference in the occurrence of lymphedema as defined by clinical observation and/or treatment: 29.4% with ALND and 14.6% with radiation (P less than .0001).
Dr. Rutgers reported that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.
SOURCE: Rutgers EJT et al. SABCS 2018, Abstract GS4-01.
REPORTING FROM SABCS 2018
Key clinical point: In patients with a positive sentinel node, axillary radiation has similar efficacy to axillary lymph node dissection and less morbidity.
Major finding: Compared with axillary lymph node dissection, axillary radiation therapy had a similar 10-year cumulative incidence of axillary recurrence (1.82% vs. 0.93%; P = .365) and half the 5-year rate of lymphedema (14.6% vs. 29.4%; P less than .0001).
Study details: A phase 3, noninferiority, randomized, controlled trial among 1,425 women with early-stage breast cancer and a positive sentinel node.
Disclosures: Dr. Rutgers reported that he had no relevant conflicts of interest. The study was supported by the European Organization for Research and Treatment of Cancer Charitable Trust.
Source: Rutgers EJT et al. SABCS 2018, Abstract GS4-01.
Oxybutynin nets dramatic reduction in hot flashes
SAN ANTONIO – Oxybutynin (Ditropan), a drug approved to treat overactive bladder, is highly efficacious and well tolerated when used to alleviate hot flashes, according to results of a randomized, controlled trial of 150 women reported by lead author Roberto A. Leon-Ferre, MD.
The women, about two-thirds of whom were breast cancer survivors taking tamoxifen or aromatase inhibitors, were having at least 28 hot flashes weekly at baseline. Results of the trial showed that the 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups).
There also was a significant difference in quality of life in favor of the drug and, in the higher-dose group, significantly better scores for mood and life enjoyment. In a video interview, Dr. Leon-Ferre discussed how oxybutynin compares with other available treatment options, which women are good or poor candidates for this drug, and how the findings have influenced his own practice.
Dr. Leon-Ferre of the Mayo Clinic, Rochester, Minn., disclosed that he had no relevant conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SAN ANTONIO – Oxybutynin (Ditropan), a drug approved to treat overactive bladder, is highly efficacious and well tolerated when used to alleviate hot flashes, according to results of a randomized, controlled trial of 150 women reported by lead author Roberto A. Leon-Ferre, MD.
The women, about two-thirds of whom were breast cancer survivors taking tamoxifen or aromatase inhibitors, were having at least 28 hot flashes weekly at baseline. Results of the trial showed that the 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups).
There also was a significant difference in quality of life in favor of the drug and, in the higher-dose group, significantly better scores for mood and life enjoyment. In a video interview, Dr. Leon-Ferre discussed how oxybutynin compares with other available treatment options, which women are good or poor candidates for this drug, and how the findings have influenced his own practice.
Dr. Leon-Ferre of the Mayo Clinic, Rochester, Minn., disclosed that he had no relevant conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
SAN ANTONIO – Oxybutynin (Ditropan), a drug approved to treat overactive bladder, is highly efficacious and well tolerated when used to alleviate hot flashes, according to results of a randomized, controlled trial of 150 women reported by lead author Roberto A. Leon-Ferre, MD.
The women, about two-thirds of whom were breast cancer survivors taking tamoxifen or aromatase inhibitors, were having at least 28 hot flashes weekly at baseline. Results of the trial showed that the 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups).
There also was a significant difference in quality of life in favor of the drug and, in the higher-dose group, significantly better scores for mood and life enjoyment. In a video interview, Dr. Leon-Ferre discussed how oxybutynin compares with other available treatment options, which women are good or poor candidates for this drug, and how the findings have influenced his own practice.
Dr. Leon-Ferre of the Mayo Clinic, Rochester, Minn., disclosed that he had no relevant conflicts of interest. The study was funded by the Breast Cancer Research Foundation.
REPORTING FROM SABCS 2018
Extent of breast surgery is tied to quality of life among young breast cancer survivors
SAN ANTONIO – Younger breast cancer patients who undergo unilateral or bilateral mastectomy report lower breast satisfaction and poorer psychosocial and sexual well-being than counterparts who undergo breast-conserving surgery, finds a cross-sectional cohort study presented by lead investigator Laura S. Dominici, MD, FACS, at the San Antonio Breast Cancer Symposium.
The 560 women studied had a mean age of 37 years and had completed the BREAST-Q questionnaire a median of 5.8 years after their breast cancer diagnosis. Results showed that the mean score for satisfaction with breasts was 65.5 with breast-conserving surgery, 59.3 with unilateral mastectomy, and 60.4 with bilateral mastectomy (P = .008). The mastectomy groups also had poorer scores for psychosocial well-being (P less than .001) and sexual well-being (P less than .001), but not physical well-being. Most of the differences remained significant in meta-analysis. In a video interview, Dr. Dominici, of Dana-Farber Cancer Institute, Boston, discussed worry and anxiety about recurrence and second cancers as drivers of choosing mastectomy, generalizability of the study’s findings, and strategies for incorporating this new information into counseling and shared decision making.
Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.
SAN ANTONIO – Younger breast cancer patients who undergo unilateral or bilateral mastectomy report lower breast satisfaction and poorer psychosocial and sexual well-being than counterparts who undergo breast-conserving surgery, finds a cross-sectional cohort study presented by lead investigator Laura S. Dominici, MD, FACS, at the San Antonio Breast Cancer Symposium.
The 560 women studied had a mean age of 37 years and had completed the BREAST-Q questionnaire a median of 5.8 years after their breast cancer diagnosis. Results showed that the mean score for satisfaction with breasts was 65.5 with breast-conserving surgery, 59.3 with unilateral mastectomy, and 60.4 with bilateral mastectomy (P = .008). The mastectomy groups also had poorer scores for psychosocial well-being (P less than .001) and sexual well-being (P less than .001), but not physical well-being. Most of the differences remained significant in meta-analysis. In a video interview, Dr. Dominici, of Dana-Farber Cancer Institute, Boston, discussed worry and anxiety about recurrence and second cancers as drivers of choosing mastectomy, generalizability of the study’s findings, and strategies for incorporating this new information into counseling and shared decision making.
Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.
SAN ANTONIO – Younger breast cancer patients who undergo unilateral or bilateral mastectomy report lower breast satisfaction and poorer psychosocial and sexual well-being than counterparts who undergo breast-conserving surgery, finds a cross-sectional cohort study presented by lead investigator Laura S. Dominici, MD, FACS, at the San Antonio Breast Cancer Symposium.
The 560 women studied had a mean age of 37 years and had completed the BREAST-Q questionnaire a median of 5.8 years after their breast cancer diagnosis. Results showed that the mean score for satisfaction with breasts was 65.5 with breast-conserving surgery, 59.3 with unilateral mastectomy, and 60.4 with bilateral mastectomy (P = .008). The mastectomy groups also had poorer scores for psychosocial well-being (P less than .001) and sexual well-being (P less than .001), but not physical well-being. Most of the differences remained significant in meta-analysis. In a video interview, Dr. Dominici, of Dana-Farber Cancer Institute, Boston, discussed worry and anxiety about recurrence and second cancers as drivers of choosing mastectomy, generalizability of the study’s findings, and strategies for incorporating this new information into counseling and shared decision making.
Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.
REPORTING FROM SABCS 2018
pCR may obviate need for adjuvant chemotherapy
SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.
“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”
The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.
“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”
“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”
Study details
For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.
Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.
Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.
Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.
The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.
Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).
Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.
“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.
Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.
SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.
“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”
The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.
“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”
“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”
Study details
For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.
Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.
Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.
Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.
The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.
Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).
Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.
“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.
Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.
SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may be able to safely skip adjuvant chemotherapy, suggest new data from a patient-level meta-analysis reported in a session and press conference at the San Antonio Breast Cancer Symposium.
“The focus of many breast cancer trials for several years has been on adding additional systemic therapies to reduce recurrence risk. However, adding therapies can result in additional toxicity and overtreatment for many patients,” noted lead investigator Laura M. Spring, MD, of Massachusetts General Hospital Cancer Center and Harvard Medical School, both in Boston. “The neoadjuvant chemotherapy model offers several additional clinical and research advantages over adjuvant chemotherapy, including the rapid evaluation of treatment response utilizing surrogate biomarkers, such as pathological complete response.”
The meta-analysis of 52 studies, which included a total of 27,895 women who were given neoadjuvant chemotherapy, confirmed a large positive prognostic effect of pCR on outcomes in the entire sample, with a 69% relative reduction in event-free survival (EFS) events and a 78% relative reduction in risk of death, a pattern that was consistent across clinical subtypes of breast cancer. More importantly, among those achieving a pCR, EFS did not differ significantly whether they went on to receive more chemotherapy after surgery or not.
“Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved EFS and overall survival, particularly for triple-negative and HER2-positive breast cancer. The results are highly significant despite inclusion of a variety of neoadjuvant regimens, suggesting the path taken to attain a pCR may not be critical,” Dr. Spring proposed. “The similar outcomes with or without adjuvant chemotherapy in patients who attained pCR after neoadjuvant chemotherapy likely reflects tumor biology and suggests adjuvant chemotherapy could potentially be omitted in certain circumstances. Further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response.”
“Basically, it appears that the impact of chemotherapy is going to be early, or if you use it early, you really don’t lose the impact [that it has] if you wait until after surgery,” commented SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of Oncology Programs at UT Southwestern Medical Center, Dallas, Texas. “So if it was me, I would have it done before the operation, frankly, because at a minimum, it’s not worse than delaying it until after surgery – at a minimum. And you get the benefit of potential breast conservation, a lesser surgery.”
Study details
For the meta-analysis, Dr. Spring and her coinvestigators searched for published studies of localized breast cancer that had 25 patients or more, featured neoadjuvant chemotherapy, and reported pCR using definitions allowed by the FDA (ypT0 ypN0 or ypT0/is ypN0), as well as recurrence and/or survival based on pathologic outcome. They excluded studies reporting only local recurrence and those using neoadjuvant endocrine therapy or neoadjuvant radiation.
Results showed that the pCR rate averaged 21.1% for the entire study population, according to Dr. Spring. But there was wide variation by tumor subtype, as expected, with a rate of less than 10% for hormone receptor–positive/HER2-negative breast cancer, to rates in the mid-30% range for triple-negative breast cancer and HER2-positive breast cancer.
Women who had pCR after neoadjuvant chemotherapy had a significantly lower risk of EFS events than peers who had residual disease (hazard ratio, 0.31; 95% probability interval, 0.24-0.39). The corresponding 5-year EFS rates were 88% and 67%.
Similarly, women who had pCR had a significantly lower risk of death (HR, 0.22; 95% probability interval, 0.15-0.30). The corresponding 5-year overall survival rates were 94% and 75%.
The EFS benefit of pCR versus residual disease was consistently seen across subgroups with triple-negative breast cancer (90% vs. 57%), HER2-positive breast cancer (86% vs. 63%), and hormone receptor–positive/HER2-negative breast cancer (97% vs. 88%). Findings were essentially the same for overall survival, according to Dr. Spring.
Among patients attaining pCR, the 5-year EFS rate was 86% for those who went on to receive adjuvant chemotherapy (HR, 0.36; 95% probability interval, 0.19-0.67) and 88% for those who did not (HR, 0.36; 95% probability interval, 0.27-0.54). The difference in hazard ratios between groups was not significant (P = .60).
Finally, the investigators conducted modeling to assess how the change in pCR rate corresponded with the change in EFS benefit. “This approach could be helpful in the design of neoadjuvant studies,” Dr. Spring explained.
“Assuming pCR is a valid surrogate endpoint, this is, it mediates all treatment effects, and that the average pCR is 50%, the magnitude of pCR change is predictive of treatment effects on EFS within a certain amount of uncertainty, based on the model,” she reported. For example, a change in pCR of 0.3 had a corresponding HR of 0.72, with a 95% probability interval of 0.68-0.77.
Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
SOURCE: Spring LM et al. SABCS 2018, Abstract GS2-03.
REPORTING FROM SABCS 2018
Key clinical point: Adjuvant chemotherapy does not further improve outcome after a pathological complete response to neoadjuvant chemotherapy.
Major finding: Patients achieving pCR had a similar reduction in risk of EFS events whether they went on to receive adjuvant chemotherapy (hazard ratio, 0.36) or not (hazard ratio, 0.36; P = .60 for difference between groups).
Study details: Individual-level meta-analysis of 27,895 patients who received neoadjuvant chemotherapy for localized breast cancer.
Disclosures: Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
Source: Spring LM et al. SABCS 2018, Abstract GS2-03.