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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.
Dr. Ingrid A. Mayer on neoadjuvant endocrine therapy: The times are changing
SAN ANTONIO – Phase 2 neoadjuvant endocrine therapy breast cancer trials can and should serve as a testing platform to inform the design of phase 3 trials with the ability to change practice, according to Ingrid A. Mayer, MD.
Correlating outcomes such as the Preoperative Endocrine Prognostic Index and Ki67 blood levels from phase 2 trials to larger, similarly designed trials could reduce costs, time, and the need for large numbers of patients, thereby promoting more efficient development of effective breast cancer therapies, she said during a plenary lecture at the San Antonio Breast Cancer Symposium.
In this video interview, Dr. Mayer, director of breast medical oncology at Vanderbilt University, Nashville, Tenn., explained that while neoadjuvant endocrine therapy is suitable for down-staging tumors in women with stage I-III breast cancer, it is not commonly used, as those patients are also good surgery candidates.
However, neoadjuvant endocrine therapy can be “an incredible platform” to test novel combinations of endocrine therapy agents with or without targeted treatments, validate new biomarkers, discover mechanisms of resistance, and predict the best combinations for moving forward in phase 3 trials, she said, adding that “this is something that all academic institutions potentially should be doing.”
Although the direct clinical benefit for patients who participate in such trials is not tremendous, participation has the potential to ultimately improve outcomes for participants and for “their friends and families and daughters,” and to help propel the science forward, Dr. Meyer noted.
“I would argue that we really should be moving forward to designing trials in the neoadjuvant endocrine setting more and more, and really utilizing this platform for that end,” she said.
Dr. Mayer reported having no relevant disclosures.
SAN ANTONIO – Phase 2 neoadjuvant endocrine therapy breast cancer trials can and should serve as a testing platform to inform the design of phase 3 trials with the ability to change practice, according to Ingrid A. Mayer, MD.
Correlating outcomes such as the Preoperative Endocrine Prognostic Index and Ki67 blood levels from phase 2 trials to larger, similarly designed trials could reduce costs, time, and the need for large numbers of patients, thereby promoting more efficient development of effective breast cancer therapies, she said during a plenary lecture at the San Antonio Breast Cancer Symposium.
In this video interview, Dr. Mayer, director of breast medical oncology at Vanderbilt University, Nashville, Tenn., explained that while neoadjuvant endocrine therapy is suitable for down-staging tumors in women with stage I-III breast cancer, it is not commonly used, as those patients are also good surgery candidates.
However, neoadjuvant endocrine therapy can be “an incredible platform” to test novel combinations of endocrine therapy agents with or without targeted treatments, validate new biomarkers, discover mechanisms of resistance, and predict the best combinations for moving forward in phase 3 trials, she said, adding that “this is something that all academic institutions potentially should be doing.”
Although the direct clinical benefit for patients who participate in such trials is not tremendous, participation has the potential to ultimately improve outcomes for participants and for “their friends and families and daughters,” and to help propel the science forward, Dr. Meyer noted.
“I would argue that we really should be moving forward to designing trials in the neoadjuvant endocrine setting more and more, and really utilizing this platform for that end,” she said.
Dr. Mayer reported having no relevant disclosures.
SAN ANTONIO – Phase 2 neoadjuvant endocrine therapy breast cancer trials can and should serve as a testing platform to inform the design of phase 3 trials with the ability to change practice, according to Ingrid A. Mayer, MD.
Correlating outcomes such as the Preoperative Endocrine Prognostic Index and Ki67 blood levels from phase 2 trials to larger, similarly designed trials could reduce costs, time, and the need for large numbers of patients, thereby promoting more efficient development of effective breast cancer therapies, she said during a plenary lecture at the San Antonio Breast Cancer Symposium.
In this video interview, Dr. Mayer, director of breast medical oncology at Vanderbilt University, Nashville, Tenn., explained that while neoadjuvant endocrine therapy is suitable for down-staging tumors in women with stage I-III breast cancer, it is not commonly used, as those patients are also good surgery candidates.
However, neoadjuvant endocrine therapy can be “an incredible platform” to test novel combinations of endocrine therapy agents with or without targeted treatments, validate new biomarkers, discover mechanisms of resistance, and predict the best combinations for moving forward in phase 3 trials, she said, adding that “this is something that all academic institutions potentially should be doing.”
Although the direct clinical benefit for patients who participate in such trials is not tremendous, participation has the potential to ultimately improve outcomes for participants and for “their friends and families and daughters,” and to help propel the science forward, Dr. Meyer noted.
“I would argue that we really should be moving forward to designing trials in the neoadjuvant endocrine setting more and more, and really utilizing this platform for that end,” she said.
Dr. Mayer reported having no relevant disclosures.
REPORTING FROM SABCS 2018
DTCs in marrow herald worse outcomes for early breast cancer
SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.
The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.
“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.
The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.
The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.
The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.
Patients were defined as being DTC positive if one or more DTCs were detected.
A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).
At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).
Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).
In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.
“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.
There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).
“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.
Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.
SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.
SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.
The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.
“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.
The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.
The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.
The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.
Patients were defined as being DTC positive if one or more DTCs were detected.
A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).
At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).
Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).
In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.
“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.
There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).
“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.
Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.
SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.
SAN ANTONIO – When disseminated tumor cells – even a single cell – are detected in the bone marrow of patients with early breast cancer, it’s not a good sign, according to results of pooled international analysis.
The presence of disseminated tumor cells (DTCs) in marrow at the time of primary diagnosis was an independent prognostic factor for overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS), reported Andreas Daniel Hartkopf, MD, MSc, of the University of Tübingen, Germany, on behalf of colleagues in the PADDY study.
“The DTC detection was associated with higher local tumor burden and more aggressive biological subtype,” he said at the San Antonio Breast Cancer Symposium.
The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is an international cooperative effort designed to evaluate the association between DTC detection in patients with early breast cancer and clinical outcomes.
The investigators collected individual data sets including information on bone marrow samples from 10,307 patients treated at 11 centers in the United States and Europe.
The patients had early invasive breast cancer (T1-4, NO-3, M0) and for inclusion in the study had to have had bone marrow aspiration performed at the time of diagnosis or during primary surgery, with no prior systemic therapy. DTCs were detected by cytokeratin staining.
Patients were defined as being DTC positive if one or more DTCs were detected.
A total of 2,814 of the 10,307 patients (27.3%) were DTC positive. DTC status was not significantly associated with menopausal status or tumor histology (invasive ductal, invasive lobular, or other), but was positively associated with tumor grade, with 21.1% of patients with grade 1 tumors being DTC positive, compared with 27.2% with grade 2 tumors, and 29.9% with grade 3 tumors (P less than .001).
At a median follow-up of 7.6 years from bone marrow sampling DTC positivity was significantly associated with, in addition to higher tumor grade, higher T stage, nodal positivity, estrogen and progesterone receptor negativity, and HER2 positivity (P less than .001 for all).
Univariate analysis showed that DTC-positive patients had significantly shorter OS, breast cancer–specific survival, and DDFS compared with DTC negative patients (P less than .001 for all).
In a multivariate model stratified by center and controlling for age, menopausal status, histology, tumor size, nodal status, and biological subtype, DTC was an independent prognostic marker for OS (hazard ratio 1.23, P = .006), DFS (HR 1.30, P less than .001) and DDFS (HR 1.30, P = .006), but not for locoregional relapse-free survival.
“These results confirm that DTC detection is an independent risk factor for metastatic relapse and poor overall survival in early breast cancer,” Dr. Hartkopf said.
There was a statistically significant interaction between DTCs and subtypes with regard to DDFS, with a HR of 2.34 for patients with luminal B disease (P = .014).
“Future trials must evaluate the predictive value of DTC detection and/or their characterization on adjuvant therapy efficacy,” Dr. Hartkopf concluded.
Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.
SOURCE: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.
REPORTING FROM SABCS 2018
Key clinical point: The presence of even a single DTC may be prognostic of metastases and poor survival.
Major finding: DTC was an independent prognostic marker for overall survival, disease-free survival, and distant disease-free survival.
Study details: Retrospective analysis of data on 10,030 patients, including 2,814 with detectable DTCs in bone marrow.
Disclosures: Dr. Hartkopf did not disclose a study funding source or potential conflicts of interest.
Source: Hartkopf AD et al. SABCS 2018. Abstract GS5-07.
Exercise during adjuvant breast cancer therapy improves CV outcomes
SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
The overall change in VO2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.
Among patients receiving chemotherapy, the VO2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.
Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m2, and a mean VO2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO2max at baseline.
They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.
Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.
In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.
“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.
Dr. Thune reported having no disclosures.
SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
The overall change in VO2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.
Among patients receiving chemotherapy, the VO2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.
Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m2, and a mean VO2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO2max at baseline.
They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.
Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.
In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.
“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.
Dr. Thune reported having no disclosures.
SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
The overall change in VO2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.
Among patients receiving chemotherapy, the VO2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.
Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m2, and a mean VO2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO2max at baseline.
They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.
Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.
In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.
“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.
Dr. Thune reported having no disclosures.
REPORTING FROM SABCS 2018
Key clinical point: An exercise program during adjuvant breast cancer treatment improves cardiovascular outcomes.
Major finding: The rate of VO2max change at 12 months was +0.3% in the exercise group versus –8.9% in the control group.
Study details: EBBA-II, a randomized trial of 546 women.
Disclosures: Dr. Thune reported having no disclosures.
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.
Extended anastrozole improves DFS, distant DFS
SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).
After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.
The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.
“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).
Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.
Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.
Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.
The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.
Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.
SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.
SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).
After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.
The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.
“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).
Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.
Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.
Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.
The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.
Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.
SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.
SAN ANTONIO – Extending treatment with adjuvant anastrozole (Arimidex) to 10 years led to significantly higher rates of disease-free and distant disease-free survival in postmenopausal women with hormone receptor–positive breast cancer in the prospective, randomized, open-label phase 3 Arimidex Extended Adjuvant Randomized Study (AERAS).
After a median of 4.9 years of follow-up, the primary endpoint of disease-free survival (DFS) was 91.9% in 840 women who were randomized to continue receiving anastrozole for an additional 5 years versus 84.4% in 843 who stopped after the initial 5 years (hazard ratio, 0.548; P = .0004), Shoichiro Ohtani, MD, reported at the San Antonio Breast Cancer Symposium.
The rate of 5-year distant DFS was 97.2% vs. 94.3% in the groups, respectively (HR, 0.514; P = .0077), said Dr. Ohtani, of Hiroshima City (Japan) Hiroshima Citizens Hospital.
“As we expected, there was no difference between the two groups in overall survival,” he said; overall survival was 99.5% and 99.6% in the groups, respectively (HR, 1.389; P = .665).
Study subjects were postmenopausal patients with stages I-III hormone receptor-positive breast cancer (HR+ BC) with a median age of 64 years who were disease-free after 5 years of either anastrozole alone or tamoxifen for 2-3 years followed by anastrozole 2-3 years. They were enrolled between November 2007 and November 2012.
Treatment with an aromatase inhibitor such as anastrozole for up to 5 years either as up-front monotherapy or after 2-3 years of tamoxifen therapy is the treatment of choice for HR+ BC in postmenopausal women, but it was thought that extending aromatase inhibitor therapy to 10 years might reduce the risk of breast cancer recurrence, Dr. Ohtani explained.
Indeed, while women randomized to extended anastrozole treatment in the current study experienced more bone-related adverse events, including arthralgia (19.2% vs. 11.7%), stiff joints (11.7% vs. 4.9%), bone fractures (2.8% vs. 1.1%), and new-onset osteoporosis (33% vs. 28%) than did those in the group that stopped anastrozole at 5 years, extended treatment significantly reduced recurrence rates.
The findings show that extended adjuvant anastrozole treatment for an additional 5 years after initial treatment is safe and provides important DFS and distant DFS benefits, he concluded.
Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis,and Ezai.
SOURCE: Ohtani S et al. SABCS 2018, Abstract GS3-04.
REPORTING FROM SABCS 2018
Key clinical point: Extending treatment with adjuvant anastrozole to 10 years improves disease free survival and distant DFS in HR+ breast cancer.
Major finding: DFS was 91.9% in patients who continued anastrozole versus 84.4% in those who stopped anastrozole after the initial 5 years (hazard ratio, 0.548; P = .0004).
Study details: A prospective, randomized, open-label, phase 3 study of 1,683 patients.
Disclosures: Dr. Ohtani has received speaker fees from CHUGAI, Astra Zeneca, Novartis, and Ezai.
Source: Ohtani S et al. SABCS 2018, Abstract GS3-04.
Tamoxifen at 5 mg halves recurrence of breast intraepithelial neoplasia
SAN ANTONIO – Good old tamoxifen, there’s life in the old girl yet: A 3-year course of low-dose tamoxifen – one-fourth of the standard dose – reduced the risk of breast intraepithelial neoplasia (IEN) recurrence by half, compared with placebo.
And although the patient numbers were relatively small, tamoxifen at 5 mg/day also reduced the risk of contralateral breast cancer by 75%, results of the TAM01 study showed.
Among 500 patients with either atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) randomized either to tamoxifen 5 mg/day for 3 years or placebo, there were 28 cases of either invasive breast cancer or recurrent DCIS in patients after a median follow-up of 5.1 years for patients assigned to placebo, compared with 14 events for patients assigned to tamoxifen, translating into a hazard ratio of 0.48 (P = .024), reported Andrea De Censi, MD, from Ospidali Galliera in Genoa, Italy, at the San Antonio Breast Cancer Symposium.
“We think our results have external validity because of the pragmatic nature of the study and the easy accessibility of the drug, and so they are generalizable,” he said, adding that “our findings are applicable in clinical practice from tomorrow [on].”
Despite concerns about the known carcinogenic and cardiovascular side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis (DVT)/pulmonary embolism between the groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen.
IEN accounts for approximately 15%-25% of all breast neoplasms. Although tamoxifen has a long track record of efficacy in prevention of recurrence, its side effects, including increased risk of endometrial cancer and thrombotic events as well as menopausal-type symptoms, have dissuaded some clinicians from prescribing it and scared some patients away from taking it.
Dr. De Censi and his colleagues conducted a phase 3 trial comparing tamoxifen 5 mg daily with placebo in 500 women with hormone-sensitive breast IEN following surgery. Women with grade 3 disease, positive margins, or comedo/necrosis DCIS received radiotherapy.
The patients were followed every 6 months, and had annual mammograms for at least 5 years after randomization.
As noted before, after 5.1 years median follow-up the primary endpoint of invasive breast cancer or DCIS had occurred in 28 patients on placebo versus 14 on tamoxifen, for an HR of 0.48. The respective incidences of contralateral breast cancer were 12 and 3, translating into a HR for tamoxifen at 0.24 (P = .018).
There were no statistically significant differences in serious adverse events between groups, including endometrial cancer (one in the tamoxifen group vs. one in the placebo group), DVT/PE (one in each group), other neoplasms (four vs. six cases, respectively), coronary heart disease (two cases each), other nonfatal events (three vs. five), or deaths (one vs. two).
“If we compare these findings with the NSABP-P1 prevention trial with a dose of 20 mg per day we would expect 2.7 endometrial cancers on tamoxifen, and 2.4 DVT or pulmonary emboli,” Dr. De Censi said in a briefing prior to his presentation of the data in a general session.
Patient-reported daily hot flashes occurred slightly but significantly more often with tamoxifen (P = .05). But when the frequency of reported hot flashes was multiplied by the intensity, the difference between the arms was not significant.
There were no significant differences between the groups for the patient-reported outcomes of vaginal dryness or pain at intercourse, or of musculoskeletal pain/arthralgia. Treatment adherence over 3 years did not differ between the groups.
Dr. De Censi noted that because 5 mg tablets of tamoxifen are not currently available, investigators recommend either cutting 10 mg tablets in half or taking the 10-mg dose every other day.
Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated the briefing, commented that the study provides valuable information about the dosing of this time-tested drug.
“When you look at drug development, in many cases we rush these drugs out and we don’t pay attention to the dose that’s needed – we pay attention to the dose that’s not very toxic, and so many of the drugs that we use we end up using them at higher doses than we need to use them,” she said.
“A drug doesn’t work if you don’t take it, and so if you can find ways to take the drug, like in giving it at lower doses, then these women are going to benefit,” Dr. Kaklamani added.
She said that based on these data she would “definitely” give patients with ADH and LCIS lower doses of tamoxifen, and while she wants to see more data on DCIS patients with further follow-up, “if I have a DCIS patient who’s not tolerating tamoxifen at the 20 mg dose, I’d be extremely happy lowering to 5 mg.”
Sandhya Pruthi, MD, from the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, said in an interview that, while she was impressed by both the reduction in risk and the favorable side effect profile, the patient sample was too small to draw firm conclusions.
“Could I go back to the clinic and tell all my patients who are taking 20 mg of tamoxifen that you can now cut your dose in half to 10 mg or even to the 5-mg dose based on this trial? That would I think be a little premature,” she said.
“Where I would like to go with this is that we do a larger trial – a randomized, controlled trial,” Dr. Pruthi added.
The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest. Dr. Kaklamani and Dr. Pruthi reported no relevant conflicts of interest.
SOURCE: De Censi A et al. SABCS 2018, Abstract GS3-01.
SAN ANTONIO – Good old tamoxifen, there’s life in the old girl yet: A 3-year course of low-dose tamoxifen – one-fourth of the standard dose – reduced the risk of breast intraepithelial neoplasia (IEN) recurrence by half, compared with placebo.
And although the patient numbers were relatively small, tamoxifen at 5 mg/day also reduced the risk of contralateral breast cancer by 75%, results of the TAM01 study showed.
Among 500 patients with either atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) randomized either to tamoxifen 5 mg/day for 3 years or placebo, there were 28 cases of either invasive breast cancer or recurrent DCIS in patients after a median follow-up of 5.1 years for patients assigned to placebo, compared with 14 events for patients assigned to tamoxifen, translating into a hazard ratio of 0.48 (P = .024), reported Andrea De Censi, MD, from Ospidali Galliera in Genoa, Italy, at the San Antonio Breast Cancer Symposium.
“We think our results have external validity because of the pragmatic nature of the study and the easy accessibility of the drug, and so they are generalizable,” he said, adding that “our findings are applicable in clinical practice from tomorrow [on].”
Despite concerns about the known carcinogenic and cardiovascular side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis (DVT)/pulmonary embolism between the groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen.
IEN accounts for approximately 15%-25% of all breast neoplasms. Although tamoxifen has a long track record of efficacy in prevention of recurrence, its side effects, including increased risk of endometrial cancer and thrombotic events as well as menopausal-type symptoms, have dissuaded some clinicians from prescribing it and scared some patients away from taking it.
Dr. De Censi and his colleagues conducted a phase 3 trial comparing tamoxifen 5 mg daily with placebo in 500 women with hormone-sensitive breast IEN following surgery. Women with grade 3 disease, positive margins, or comedo/necrosis DCIS received radiotherapy.
The patients were followed every 6 months, and had annual mammograms for at least 5 years after randomization.
As noted before, after 5.1 years median follow-up the primary endpoint of invasive breast cancer or DCIS had occurred in 28 patients on placebo versus 14 on tamoxifen, for an HR of 0.48. The respective incidences of contralateral breast cancer were 12 and 3, translating into a HR for tamoxifen at 0.24 (P = .018).
There were no statistically significant differences in serious adverse events between groups, including endometrial cancer (one in the tamoxifen group vs. one in the placebo group), DVT/PE (one in each group), other neoplasms (four vs. six cases, respectively), coronary heart disease (two cases each), other nonfatal events (three vs. five), or deaths (one vs. two).
“If we compare these findings with the NSABP-P1 prevention trial with a dose of 20 mg per day we would expect 2.7 endometrial cancers on tamoxifen, and 2.4 DVT or pulmonary emboli,” Dr. De Censi said in a briefing prior to his presentation of the data in a general session.
Patient-reported daily hot flashes occurred slightly but significantly more often with tamoxifen (P = .05). But when the frequency of reported hot flashes was multiplied by the intensity, the difference between the arms was not significant.
There were no significant differences between the groups for the patient-reported outcomes of vaginal dryness or pain at intercourse, or of musculoskeletal pain/arthralgia. Treatment adherence over 3 years did not differ between the groups.
Dr. De Censi noted that because 5 mg tablets of tamoxifen are not currently available, investigators recommend either cutting 10 mg tablets in half or taking the 10-mg dose every other day.
Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated the briefing, commented that the study provides valuable information about the dosing of this time-tested drug.
“When you look at drug development, in many cases we rush these drugs out and we don’t pay attention to the dose that’s needed – we pay attention to the dose that’s not very toxic, and so many of the drugs that we use we end up using them at higher doses than we need to use them,” she said.
“A drug doesn’t work if you don’t take it, and so if you can find ways to take the drug, like in giving it at lower doses, then these women are going to benefit,” Dr. Kaklamani added.
She said that based on these data she would “definitely” give patients with ADH and LCIS lower doses of tamoxifen, and while she wants to see more data on DCIS patients with further follow-up, “if I have a DCIS patient who’s not tolerating tamoxifen at the 20 mg dose, I’d be extremely happy lowering to 5 mg.”
Sandhya Pruthi, MD, from the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, said in an interview that, while she was impressed by both the reduction in risk and the favorable side effect profile, the patient sample was too small to draw firm conclusions.
“Could I go back to the clinic and tell all my patients who are taking 20 mg of tamoxifen that you can now cut your dose in half to 10 mg or even to the 5-mg dose based on this trial? That would I think be a little premature,” she said.
“Where I would like to go with this is that we do a larger trial – a randomized, controlled trial,” Dr. Pruthi added.
The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest. Dr. Kaklamani and Dr. Pruthi reported no relevant conflicts of interest.
SOURCE: De Censi A et al. SABCS 2018, Abstract GS3-01.
SAN ANTONIO – Good old tamoxifen, there’s life in the old girl yet: A 3-year course of low-dose tamoxifen – one-fourth of the standard dose – reduced the risk of breast intraepithelial neoplasia (IEN) recurrence by half, compared with placebo.
And although the patient numbers were relatively small, tamoxifen at 5 mg/day also reduced the risk of contralateral breast cancer by 75%, results of the TAM01 study showed.
Among 500 patients with either atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or lobular carcinoma in situ (LCIS) randomized either to tamoxifen 5 mg/day for 3 years or placebo, there were 28 cases of either invasive breast cancer or recurrent DCIS in patients after a median follow-up of 5.1 years for patients assigned to placebo, compared with 14 events for patients assigned to tamoxifen, translating into a hazard ratio of 0.48 (P = .024), reported Andrea De Censi, MD, from Ospidali Galliera in Genoa, Italy, at the San Antonio Breast Cancer Symposium.
“We think our results have external validity because of the pragmatic nature of the study and the easy accessibility of the drug, and so they are generalizable,” he said, adding that “our findings are applicable in clinical practice from tomorrow [on].”
Despite concerns about the known carcinogenic and cardiovascular side effects of tamoxifen, there were no significant differences in either the rate of endometrial cancer or of deep vein thrombosis (DVT)/pulmonary embolism between the groups, and there was only a borderline increase in hot flashes among patients randomized to tamoxifen.
IEN accounts for approximately 15%-25% of all breast neoplasms. Although tamoxifen has a long track record of efficacy in prevention of recurrence, its side effects, including increased risk of endometrial cancer and thrombotic events as well as menopausal-type symptoms, have dissuaded some clinicians from prescribing it and scared some patients away from taking it.
Dr. De Censi and his colleagues conducted a phase 3 trial comparing tamoxifen 5 mg daily with placebo in 500 women with hormone-sensitive breast IEN following surgery. Women with grade 3 disease, positive margins, or comedo/necrosis DCIS received radiotherapy.
The patients were followed every 6 months, and had annual mammograms for at least 5 years after randomization.
As noted before, after 5.1 years median follow-up the primary endpoint of invasive breast cancer or DCIS had occurred in 28 patients on placebo versus 14 on tamoxifen, for an HR of 0.48. The respective incidences of contralateral breast cancer were 12 and 3, translating into a HR for tamoxifen at 0.24 (P = .018).
There were no statistically significant differences in serious adverse events between groups, including endometrial cancer (one in the tamoxifen group vs. one in the placebo group), DVT/PE (one in each group), other neoplasms (four vs. six cases, respectively), coronary heart disease (two cases each), other nonfatal events (three vs. five), or deaths (one vs. two).
“If we compare these findings with the NSABP-P1 prevention trial with a dose of 20 mg per day we would expect 2.7 endometrial cancers on tamoxifen, and 2.4 DVT or pulmonary emboli,” Dr. De Censi said in a briefing prior to his presentation of the data in a general session.
Patient-reported daily hot flashes occurred slightly but significantly more often with tamoxifen (P = .05). But when the frequency of reported hot flashes was multiplied by the intensity, the difference between the arms was not significant.
There were no significant differences between the groups for the patient-reported outcomes of vaginal dryness or pain at intercourse, or of musculoskeletal pain/arthralgia. Treatment adherence over 3 years did not differ between the groups.
Dr. De Censi noted that because 5 mg tablets of tamoxifen are not currently available, investigators recommend either cutting 10 mg tablets in half or taking the 10-mg dose every other day.
Virginia Kaklamani, MD, leader of the breast cancer program at the University of Texas, San Antonio, who moderated the briefing, commented that the study provides valuable information about the dosing of this time-tested drug.
“When you look at drug development, in many cases we rush these drugs out and we don’t pay attention to the dose that’s needed – we pay attention to the dose that’s not very toxic, and so many of the drugs that we use we end up using them at higher doses than we need to use them,” she said.
“A drug doesn’t work if you don’t take it, and so if you can find ways to take the drug, like in giving it at lower doses, then these women are going to benefit,” Dr. Kaklamani added.
She said that based on these data she would “definitely” give patients with ADH and LCIS lower doses of tamoxifen, and while she wants to see more data on DCIS patients with further follow-up, “if I have a DCIS patient who’s not tolerating tamoxifen at the 20 mg dose, I’d be extremely happy lowering to 5 mg.”
Sandhya Pruthi, MD, from the Mayo Clinic in Rochester, Minnesota, who was not involved in the study, said in an interview that, while she was impressed by both the reduction in risk and the favorable side effect profile, the patient sample was too small to draw firm conclusions.
“Could I go back to the clinic and tell all my patients who are taking 20 mg of tamoxifen that you can now cut your dose in half to 10 mg or even to the 5-mg dose based on this trial? That would I think be a little premature,” she said.
“Where I would like to go with this is that we do a larger trial – a randomized, controlled trial,” Dr. Pruthi added.
The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest. Dr. Kaklamani and Dr. Pruthi reported no relevant conflicts of interest.
SOURCE: De Censi A et al. SABCS 2018, Abstract GS3-01.
REPORTING FROM SABCS 2018
Key clinical point: Tamoxifen at one-fourth of the standard dose prevents invasive breast disease or ductal carcinoma in situ recurrence with toxicities, comparable with those of placebo.
Major finding: Tamoxifen at 5 mg/day reduced the risk of invasive disease or ductal carcinoma in situ by 52%, and the risk of contralateral breast cancer by 76%.
Study details: A randomized, phase 3 trial in 500 women with breast intraepithelial neoplasia.
Disclosures: The TAM01 study was supported by the Italian Ministry of Health, Italian Association for Cancer Research, and the Italian League Against Cancer. Dr. De Censi and his coauthors reported having no direct conflicts of interest. Dr. Kaklamani and Dr. Pruthi reported no relevant conflicts of interest.
Source: De Censi A et al. SABCS 2018, Abstract GS3-01.
TNBC survival appears better when adjuvant chemotherapy is delivered within 30 days
SAN ANTONIO – The longer the delay in initiating adjuvant chemotherapy, the worse the survival in patients with triple-negative breast cancer (TNBC), findings from a review of nearly 700 cases suggest.
Delays of more than 30 days between surgery and initiation of chemotherapy were associated with lower disease-free survival (DFS), distant recurrence–free survival (DRFS), and overall survival (OS), Zaida Morante, MD, reported at the San Antonio Breast Cancer Symposium.
In 687 women with clinical stage I, II, or III TNBC who were diagnosed at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, during 2000-2014 and followed for a median of 8.5 years, time to chemotherapy was less than 30 days in 189 patients (27.5%), 31-60 days in 329 patients (47.9%), 61-90 days in 115 patients (16.7%), and more than 91 days in 54 patients (7.9%), said Dr. Morante, a medical oncologist at the institute.
Overall survival at 10 years was 82% in those who received chemotherapy within 30 days of surgery, compared with 67.4%, 67.1%, and 65.1% in those treated at 31-60, 61-90, and more than 91 days after surgery, respectively, she said.
“The difference was consistent across the different periods of the evaluation,” she said during a press briefing at the symposium. “Additionally, the benefit of receiving chemotherapy within 30 days exists and is statistically significant for [nodal status] N0 and N1 (hazard ratios, 1.701 and 2.498).”
In those with N2 and N3 nodal status, there was a numerical difference, but it didn’t reach statistical significance.
DFS was also significantly worse if treated later than 30 days after surgery; those treated within 30 days had 10-year DFS of 81.4%, compared with 68.8%, 70.8%, and 68.1% in the other groups, respectively. The difference was even more pronounced for 10-year DRFS, which was 80.2%, 64.9%, 67.5%, and 58.6% in the groups, respectively.
Multivariate analyses confirmed that time to adjuvant chemotherapy was an independent prognostic factor for survival, she said, noting that compared with patients treated within 30 days of surgery, those treated at 31-60 days had 1.9-fold increased risk of death, and those treated at 61-90 days had a 2.4-fold increased risk of death.
“The difference in 10-year overall survival rates between receiving chemotherapy within 30 days after surgery and after 30 days was more than 10%,” she said. “These results represent a feasible opportunity for improving outcomes in triple-negative breast cancer patients.”
Although only 28% of patients in this review received adjuvant chemotherapy within 30 days, most patients in the United States “will fall within the 30 days and under” category, said press briefing moderator Carlos Arteaga, MD, professor and director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas.
However, the findings might suggest a greater role for neoadjuvant chemotherapy in these patients.
“Because this is systemic therapy ... it’s treating the systemic disease. I wonder if this is arguing ... that we need to have an impetus to deliver the systemic therapy as soon as we can – early, even before the operation,” he said.
Indeed, while timing isn’t everything, Dr. Morante’s findings and others presented at the meeting “highlight the possibility that perhaps it is more important than we previously suspected,” discussant Joseph A. Sparano, MD, said at the meeting, adding that the findings raise questions about current paradigms for management of breast cancer.
“We now have substantial data suggesting that the timing of adjuvant chemotherapy matters in triple-negative breast cancer, and that 30 days may be optimal,” said Dr. Sparano, professor at the Albert Einstein College of Medicine, New York.
“This doesn’t mean that patients who may not be ready for the chemotherapy because of complications related to the surgery should be forced into a situation where they are at higher risk from receiving the chemotherapy, but nevertheless, the results are important,” he said.
Dr. Morante and Dr. Arteaga each reported having no relevant conflicts of interest to declare. Dr. Sparano has received consulting fees from Roche, Eli Lilly, Novartis, Celldex, AstraZeneca, Pfizer, and Adgero. He also has ownership interests with MetaStat.
SOURCE: Morante Z et al. SABCS 2018, Abstract GS2-05.
SAN ANTONIO – The longer the delay in initiating adjuvant chemotherapy, the worse the survival in patients with triple-negative breast cancer (TNBC), findings from a review of nearly 700 cases suggest.
Delays of more than 30 days between surgery and initiation of chemotherapy were associated with lower disease-free survival (DFS), distant recurrence–free survival (DRFS), and overall survival (OS), Zaida Morante, MD, reported at the San Antonio Breast Cancer Symposium.
In 687 women with clinical stage I, II, or III TNBC who were diagnosed at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, during 2000-2014 and followed for a median of 8.5 years, time to chemotherapy was less than 30 days in 189 patients (27.5%), 31-60 days in 329 patients (47.9%), 61-90 days in 115 patients (16.7%), and more than 91 days in 54 patients (7.9%), said Dr. Morante, a medical oncologist at the institute.
Overall survival at 10 years was 82% in those who received chemotherapy within 30 days of surgery, compared with 67.4%, 67.1%, and 65.1% in those treated at 31-60, 61-90, and more than 91 days after surgery, respectively, she said.
“The difference was consistent across the different periods of the evaluation,” she said during a press briefing at the symposium. “Additionally, the benefit of receiving chemotherapy within 30 days exists and is statistically significant for [nodal status] N0 and N1 (hazard ratios, 1.701 and 2.498).”
In those with N2 and N3 nodal status, there was a numerical difference, but it didn’t reach statistical significance.
DFS was also significantly worse if treated later than 30 days after surgery; those treated within 30 days had 10-year DFS of 81.4%, compared with 68.8%, 70.8%, and 68.1% in the other groups, respectively. The difference was even more pronounced for 10-year DRFS, which was 80.2%, 64.9%, 67.5%, and 58.6% in the groups, respectively.
Multivariate analyses confirmed that time to adjuvant chemotherapy was an independent prognostic factor for survival, she said, noting that compared with patients treated within 30 days of surgery, those treated at 31-60 days had 1.9-fold increased risk of death, and those treated at 61-90 days had a 2.4-fold increased risk of death.
“The difference in 10-year overall survival rates between receiving chemotherapy within 30 days after surgery and after 30 days was more than 10%,” she said. “These results represent a feasible opportunity for improving outcomes in triple-negative breast cancer patients.”
Although only 28% of patients in this review received adjuvant chemotherapy within 30 days, most patients in the United States “will fall within the 30 days and under” category, said press briefing moderator Carlos Arteaga, MD, professor and director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas.
However, the findings might suggest a greater role for neoadjuvant chemotherapy in these patients.
“Because this is systemic therapy ... it’s treating the systemic disease. I wonder if this is arguing ... that we need to have an impetus to deliver the systemic therapy as soon as we can – early, even before the operation,” he said.
Indeed, while timing isn’t everything, Dr. Morante’s findings and others presented at the meeting “highlight the possibility that perhaps it is more important than we previously suspected,” discussant Joseph A. Sparano, MD, said at the meeting, adding that the findings raise questions about current paradigms for management of breast cancer.
“We now have substantial data suggesting that the timing of adjuvant chemotherapy matters in triple-negative breast cancer, and that 30 days may be optimal,” said Dr. Sparano, professor at the Albert Einstein College of Medicine, New York.
“This doesn’t mean that patients who may not be ready for the chemotherapy because of complications related to the surgery should be forced into a situation where they are at higher risk from receiving the chemotherapy, but nevertheless, the results are important,” he said.
Dr. Morante and Dr. Arteaga each reported having no relevant conflicts of interest to declare. Dr. Sparano has received consulting fees from Roche, Eli Lilly, Novartis, Celldex, AstraZeneca, Pfizer, and Adgero. He also has ownership interests with MetaStat.
SOURCE: Morante Z et al. SABCS 2018, Abstract GS2-05.
SAN ANTONIO – The longer the delay in initiating adjuvant chemotherapy, the worse the survival in patients with triple-negative breast cancer (TNBC), findings from a review of nearly 700 cases suggest.
Delays of more than 30 days between surgery and initiation of chemotherapy were associated with lower disease-free survival (DFS), distant recurrence–free survival (DRFS), and overall survival (OS), Zaida Morante, MD, reported at the San Antonio Breast Cancer Symposium.
In 687 women with clinical stage I, II, or III TNBC who were diagnosed at the Instituto Nacional de Enfermedades Neoplasicas in Lima, Peru, during 2000-2014 and followed for a median of 8.5 years, time to chemotherapy was less than 30 days in 189 patients (27.5%), 31-60 days in 329 patients (47.9%), 61-90 days in 115 patients (16.7%), and more than 91 days in 54 patients (7.9%), said Dr. Morante, a medical oncologist at the institute.
Overall survival at 10 years was 82% in those who received chemotherapy within 30 days of surgery, compared with 67.4%, 67.1%, and 65.1% in those treated at 31-60, 61-90, and more than 91 days after surgery, respectively, she said.
“The difference was consistent across the different periods of the evaluation,” she said during a press briefing at the symposium. “Additionally, the benefit of receiving chemotherapy within 30 days exists and is statistically significant for [nodal status] N0 and N1 (hazard ratios, 1.701 and 2.498).”
In those with N2 and N3 nodal status, there was a numerical difference, but it didn’t reach statistical significance.
DFS was also significantly worse if treated later than 30 days after surgery; those treated within 30 days had 10-year DFS of 81.4%, compared with 68.8%, 70.8%, and 68.1% in the other groups, respectively. The difference was even more pronounced for 10-year DRFS, which was 80.2%, 64.9%, 67.5%, and 58.6% in the groups, respectively.
Multivariate analyses confirmed that time to adjuvant chemotherapy was an independent prognostic factor for survival, she said, noting that compared with patients treated within 30 days of surgery, those treated at 31-60 days had 1.9-fold increased risk of death, and those treated at 61-90 days had a 2.4-fold increased risk of death.
“The difference in 10-year overall survival rates between receiving chemotherapy within 30 days after surgery and after 30 days was more than 10%,” she said. “These results represent a feasible opportunity for improving outcomes in triple-negative breast cancer patients.”
Although only 28% of patients in this review received adjuvant chemotherapy within 30 days, most patients in the United States “will fall within the 30 days and under” category, said press briefing moderator Carlos Arteaga, MD, professor and director of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas.
However, the findings might suggest a greater role for neoadjuvant chemotherapy in these patients.
“Because this is systemic therapy ... it’s treating the systemic disease. I wonder if this is arguing ... that we need to have an impetus to deliver the systemic therapy as soon as we can – early, even before the operation,” he said.
Indeed, while timing isn’t everything, Dr. Morante’s findings and others presented at the meeting “highlight the possibility that perhaps it is more important than we previously suspected,” discussant Joseph A. Sparano, MD, said at the meeting, adding that the findings raise questions about current paradigms for management of breast cancer.
“We now have substantial data suggesting that the timing of adjuvant chemotherapy matters in triple-negative breast cancer, and that 30 days may be optimal,” said Dr. Sparano, professor at the Albert Einstein College of Medicine, New York.
“This doesn’t mean that patients who may not be ready for the chemotherapy because of complications related to the surgery should be forced into a situation where they are at higher risk from receiving the chemotherapy, but nevertheless, the results are important,” he said.
Dr. Morante and Dr. Arteaga each reported having no relevant conflicts of interest to declare. Dr. Sparano has received consulting fees from Roche, Eli Lilly, Novartis, Celldex, AstraZeneca, Pfizer, and Adgero. He also has ownership interests with MetaStat.
SOURCE: Morante Z et al. SABCS 2018, Abstract GS2-05.
REPORTING FROM SABCS 2018
Key clinical point: Outcomes are improved with adjuvant chemotherapy within 30 days of surgery, compared with beyond 30 days, in triple-negative breast cancer.
Major finding: 10-year overall survival was 82% with chemotherapy within 30 days of surgery versus 67.4%, 67.1%, and 65.1% with chemotherapy at 31-60, 61-90, and more than 91 days after surgery, respectively.
Study details: A retrospective review of 687 cases of TNBC.
Disclosures: Dr. Morante and Dr. Arteaga each reported having no relevant conflicts of interest to declare. Dr. Sparano has received consulting fees from Roche, Eli Lilly, Novartis, Celldex, AstraZeneca, Pfizer, and Adgero. He also has ownership interests with MetaStat.
Source: Morante Z et al., SABCS 2018 Abstract GS2-05.