TBD Meeting (3274-23)

SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.

However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.

The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.

The researchers found no difference in 5-year axillary or invasive recurrence rates whether women had axillary dissections or not. The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.

Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.

“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.

However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.

Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.

So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.

Study details

The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.

Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.

Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.

Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.

Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.

The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.

The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.

The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).

Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.

“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.

The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.

SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.

However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.

The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.

The researchers found no difference in 5-year axillary or invasive recurrence rates whether women had axillary dissections or not. The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.

Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.

“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.

However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.

Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.

So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.

Study details

The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.

Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.

Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.

Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.

Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.

The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.

The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.

The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).

Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.

“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.

The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.

SAN ANTONIO — Axillary lymph node dissection is the current standard of care in breast cancer when metastases are found in sentinel lymph nodes after neoadjuvant chemotherapy.

However, what to do when isolated tumor cells instead of outright metastases are found in sentinel nodes is an open question. Some surgeons opt for a full axillary dissection while others do not, and there is no standard of care, explained Giacomo Montagna, MD, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York City.

The study led and presented by Dr. Montagna at the San Antonio Breast Cancer Symposium brings some much-needed clarity to the issue.

The researchers found no difference in 5-year axillary or invasive recurrence rates whether women had axillary dissections or not. The findings argue strongly against “routine axillary lymph node dissection” — with its considerable morbidities — “in patients with residual isolated tumor cells after neoadjuvant chemotherapy,” Dr. Montagna said.

Study discussant Elizabeth Mittendorf, MD, PhD, a breast cancer surgeon at Brigham and Women’s Hospital, Boston, agreed.

“It appears that the presence of isolated tumor cells in the sentinel nodes does not negatively impact oncologic outcomes. These additional data allow us to debunk some of the surgical dogma we grew up with, specifically that lymph node dissection is required for either survival or local control,” Dr. Mittendorf said.

However, there was concern among audience members that the information gleaned from a full dissection might still be needed to guide follow-on adjuvant therapy decisions.

Dr. Mittendorf didn’t think so. Although additional positive lymph nodes were found in almost a third of women who had axillary dissections in the review, the majority of involved nodes simply had more isolated tumor cells; macrometastases were found in just 5% of cases.

So, for most patients, additional information from axillary dissections is “unlikely needed to inform adjuvant therapy, and in fact,” based on the 5% figure, “we are thinking we would have to do well over a hundred lymph node dissections in such patients to inform treatment recommendations for fewer than five. This comes at the cost of fair morbidity,” she said.

Study details

The retrospective study, dubbed OPBC05/EUBREAST-14R/ICARO, included 583 women with cT1-4 N0-3 breast cancer treated at 62 centers in 18 countries. The majority of subjects were from the United States and Europe.

Every patient was found to have isolated tumor cells (ITCs) in their sentinel lymph nodes after neoadjuvant chemotherapy (NAC), which generally included anthracycline and taxane-based regimens. The majority of patients did not have a pathologic complete response to NAC.

Overall, 182 patients (31%) had a subsequent axillary lymph node dissection; the rest did not.

Dissections were more common in the presence of lymphovascular invasion and N2/N3 disease as well as when fewer lymph nodes were removed and when ITCs were found during surgery on frozen section, which was the case in a quarter of patients.

Additional positive nodes were found in 30% of patients in the dissection group and consisted of more nodes with ITCs in 18%, micrometastases in 7%, and macrometastases in 5%. Receptor status and nodal status at presentation did not have an impact on the likelihood of finding macrometastases.

The main finding of the study was that there were no statistically significant differences in recurrence outcomes between the two groups.

The 5-year rate of isolated axillary recurrence was 1.7% with axillary lymph node dissection (ALND) versus 1.1% without it. The 5-year rate of any invasive recurrence was 16% in the ALND arm and 19% in the no-dissection group.

The median age in the study was 48 years. The majority of patients (57%) had clinical T2 tumors. Most were HR positive and either HER2 negative (41%) or HER2 positive (28%).

Regional nodal radiation was more common in the ALND group, 82% versus 75%. The dissection arm had a mean of 2.8 sentinel lymph nodes removed versus 3.5 in the no-dissection group.

“The likelihood of finding additional positive lymph nodes in patients with residual ITCs after NAC is lower than in patients with residual micro- and macrometastases. In the majority of cases, they contain ITCs. Nodal recurrence after omission of ALND is rare in this population,” the investigators concluded in their abstract.

The work was funded by EUBREAST. Dr. Montagna doesn’t have any disclosures. Dr. Mittendorf has several industry ties, including being an advisor for Roche, AstraZeneca, and Moderna and a speaker for Merck.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Axillary lymph node dissection may be unnecessary if breast cancer patients with one or two positive sentinel lymph nodes plan to have adjuvant nodal radiation, according to a major Scandinavian trial presented at the San Antonio Breast Cancer Symposium.

“It means that you don’t need to dissect the axilla if you” are going to “radiate the axilla.” “For the U.S., that’s the conclusion because there are still centers that do both, and that’s out,” lead investigator Jana de Boniface, MD, PhD, a breast cancer surgeon at the Karolinska Institutet, Stockholm, said in an interview.

The study added to a persistent theme at this year’s meeting, protecting breast cancer patients from doing too much and causing unnecessary harm. Some even wondered if 5 years of endocrine therapy is necessary.

Dr. Boniface shared her thoughts after presenting the Scandinavian trial, SENOMAC, which she led.

SENOMAC randomized 1,204 patients with one or two positive sentinel lymph nodes to axillary dissection; 1,335 with the same finding were randomized to no dissection.

Subjects had clinically T1-3, N0 primary breast cancer. About 89% in both arms went on to adjuvant radiation, including nodal radiation, and almost all also went on to systemic therapy, which included endocrine therapy in over 90%. Only about 2% of subjects had neoadjuvant therapy.

At a median follow-up of nearly 4 years, recurrence-free survival was virtually identical in both groups, with 8% of patients in the dissection arm and 7.1% in the no-dissection group having recurrences. Estimated 5-year recurrence-free survival was just shy of 90% in both groups. Skipping dissection was strongly non-inferior to having one (P < .001).

SENOMAC “clearly shows that you don’t need to dissect the axilla if you have one to two positive sentinel lymph nodes” so long as patients have adjuvant nodal radiation. Recurrence-free survival “curves practically overlap, and we cannot see any difference between the two groups,” Dr. Boniface said.

Meanwhile, the dissection group fared worse on patient reported outcomes. Overall survival outcomes, the primary endpoint of the trial, are expected within 2 years.

The goal of the trial, the largest to date to look into the issue, was to fill gaps in the literature. Similar outcomes were reported around a decade ago in patients with low sentinel lymph node burdens, but the extensive exclusion criteria raised questions about general applicability.

In contrast, SENOMAC was widely inclusive. Over a third of patients had mastectomies, over a third had sentinel lymph node extracapsular extension, almost 6% had T3 disease, almost 20% had lobular carcinoma, 40% were 65 years or older, and tumors were as large as 15.5 cm.

The findings held regardless of those and other factors on subgroup analyses, including estrogen receptor and HER2 status and the number of additional positive nodes retrieved in the dissection group.

Andrea V. Barrio, MD, the study discussant and a breast cancer surgeon at Memorial Sloan Kettering Cancer Center, New York, agreed with the message from SENOMAC.

“Based on this, ALND [axillary lymph node dissection] should not be considered standard in patients with clinical T1-3, N0 breast cancer with one to two positive sentinel nodes, with or without microscopic extracapsular extension, undergoing lumpectomy or mastectomy,” provided nodal adjuvant radiotherapy is indicated, she said.

Although adjuvant nodal radiation for patients with one to three positive sentinel nodes is standard of care in Denmark and Sweden, where most of the patients in SENOMAC were located, practices vary widely in the United States. If adjuvant radiation isn’t used, “then ALND [is still] indicated,” Dr. Barrio said, but in either case, “only one is needed.”

In keeping with the de-escalation theme at the 2023 symposium, both Dr. Boniface and Dr. Barrio noted that trials are now underway to find patients who can avoid any axillary treatment at all if they have just one or two positive sentinel lymph nodes.

Preoperative axillary ultrasound was mandatory in SENOMAC and patients with non-palpable suspicious axillary lymph nodes were enrolled.

Thirty-six were positive on fine needle aspiration and randomized into the study, but when asked, Dr. Boniface didn’t have the data immediately at hand on how they fared.

The work was funded by the Swedish Research Council, Nordic Cancer Union, and others. Dr. Boniface and Dr. Barrio didn’t have any disclosures.

SAN ANTONIO — Researchers have likely solved the key problem with using olanzapine to prevent nausea and vomiting in chemotherapy patients.

Although it’s highly effective in combination with standard antiemetic therapy, olanzapine at the standard dose of 10 mg makes people too drowsy. “This has prevented its widespread use in clinical practice,” medical oncologist Jyoti Bajpai, DM, of Tata Memorial Cancer Centre, Mumbai, India, explained at the San Antonio Breast Cancer Symposium.

She and her colleagues had a simple idea: Reduce the dose to 2.5 mg instead of 10 mg to prevent the problem. In a randomized trial with 267 patients that Dr. Bajpai presented at the meeting, they found that the lower dose was just as effective for nausea and vomiting prophylaxis, and it greatly reduced daytime somnolence.

“This merits consideration as an antiemetic regimen of choice for highly emetogenic chemotherapy.” The findings are “practice changing,” Dr. Bajpai, the lead investigator, said.

Laura Huppert, MD, a breast oncologist at the University of California, San Francisco, wasn’t surprised by the finding.

She said she and her colleagues at UCSF use a lot of olanzapine for nausea and vomiting prophylaxis. Like the team in India, they have found that 2.5 mg is effective and causes far less sleepiness. Some patients require 5 mg, but the full 10-mg dose is rarely needed.

Although the approach is familiar at UCSF, Dr. Huppert said she doesn’t think a lot of oncologists outside of academic centers know that olanzapine is “really helpful” and that “you don’t need a high dose.” It’s “a very good clinical pearl” and “definitely a new message for some,” she said in an interview.

Over 90% of the subjects in the study were women with breast cancer. Other cancers included sarcoma, germ cell tumors, and head and neck cancer. Subjects were scheduled for their first chemotherapy session with anthracycline-cyclophosphamide and high-dose cisplatin.

The trial randomized 135 patients to 10 mg of olanzapine and 132 to 2.5mg for 5 days, starting the day of their session. They were also on standard triple-antiemetic therapy (selective serotonin receptor (5-HT3) antagonist, neurokinin-1 receptor antagonist, and single-dose dexamethasone).

There were no significant differences between the two arms regarding nausea and vomiting, which patients tracked in daily journals using symptom severity and visual analog scales.

For instance, 44.7% in the 2.5-mg arm and 43.7% in the 10-mg arm reported no vomiting, no use of rescue medications, and no or only mild nausea (P = .87). Results were similar in the first 24 hours as well as on subsequent days.

There was also no difference in the proportion of patients who did have an emetic episode or needed rescue medication: 49.2% in the 2.5-mg arm versus 48.9% with 10 mg (P = .954).

Where the two groups split was on the incidence of daytime somnolence, which was reported by 65.2% of patients in the low-dose arm but 89.6% in the standard-dose group (P < .001). During the first 24 hours, 4.5% of low-dose patients reported severe somnolence versus 40% with 10-mg dosing (P < .001).

The overall incidence declined over the remaining study days, but the differences between the two groups were comparable. On day 5, for instance, 0.8% of low-dose patients but 8.1% of standard-dose patients reported severe somnolence (P = .004).

Low-dose patients also reported less appetite suppression.

The work was supported by the Progressive Ladies Welfare Association. Dr. Bajpai didn’t have any disclosures. Dr. Huppert is an adviser for AstraZeneca.

SAN ANTONIO — Researchers have likely solved the key problem with using olanzapine to prevent nausea and vomiting in chemotherapy patients.

Although it’s highly effective in combination with standard antiemetic therapy, olanzapine at the standard dose of 10 mg makes people too drowsy. “This has prevented its widespread use in clinical practice,” medical oncologist Jyoti Bajpai, DM, of Tata Memorial Cancer Centre, Mumbai, India, explained at the San Antonio Breast Cancer Symposium.

She and her colleagues had a simple idea: Reduce the dose to 2.5 mg instead of 10 mg to prevent the problem. In a randomized trial with 267 patients that Dr. Bajpai presented at the meeting, they found that the lower dose was just as effective for nausea and vomiting prophylaxis, and it greatly reduced daytime somnolence.

“This merits consideration as an antiemetic regimen of choice for highly emetogenic chemotherapy.” The findings are “practice changing,” Dr. Bajpai, the lead investigator, said.

Laura Huppert, MD, a breast oncologist at the University of California, San Francisco, wasn’t surprised by the finding.

She said she and her colleagues at UCSF use a lot of olanzapine for nausea and vomiting prophylaxis. Like the team in India, they have found that 2.5 mg is effective and causes far less sleepiness. Some patients require 5 mg, but the full 10-mg dose is rarely needed.

Although the approach is familiar at UCSF, Dr. Huppert said she doesn’t think a lot of oncologists outside of academic centers know that olanzapine is “really helpful” and that “you don’t need a high dose.” It’s “a very good clinical pearl” and “definitely a new message for some,” she said in an interview.

Over 90% of the subjects in the study were women with breast cancer. Other cancers included sarcoma, germ cell tumors, and head and neck cancer. Subjects were scheduled for their first chemotherapy session with anthracycline-cyclophosphamide and high-dose cisplatin.

The trial randomized 135 patients to 10 mg of olanzapine and 132 to 2.5mg for 5 days, starting the day of their session. They were also on standard triple-antiemetic therapy (selective serotonin receptor (5-HT3) antagonist, neurokinin-1 receptor antagonist, and single-dose dexamethasone).

There were no significant differences between the two arms regarding nausea and vomiting, which patients tracked in daily journals using symptom severity and visual analog scales.

For instance, 44.7% in the 2.5-mg arm and 43.7% in the 10-mg arm reported no vomiting, no use of rescue medications, and no or only mild nausea (P = .87). Results were similar in the first 24 hours as well as on subsequent days.

There was also no difference in the proportion of patients who did have an emetic episode or needed rescue medication: 49.2% in the 2.5-mg arm versus 48.9% with 10 mg (P = .954).

Where the two groups split was on the incidence of daytime somnolence, which was reported by 65.2% of patients in the low-dose arm but 89.6% in the standard-dose group (P < .001). During the first 24 hours, 4.5% of low-dose patients reported severe somnolence versus 40% with 10-mg dosing (P < .001).

The overall incidence declined over the remaining study days, but the differences between the two groups were comparable. On day 5, for instance, 0.8% of low-dose patients but 8.1% of standard-dose patients reported severe somnolence (P = .004).

Low-dose patients also reported less appetite suppression.

The work was supported by the Progressive Ladies Welfare Association. Dr. Bajpai didn’t have any disclosures. Dr. Huppert is an adviser for AstraZeneca.

SAN ANTONIO — Researchers have likely solved the key problem with using olanzapine to prevent nausea and vomiting in chemotherapy patients.

Although it’s highly effective in combination with standard antiemetic therapy, olanzapine at the standard dose of 10 mg makes people too drowsy. “This has prevented its widespread use in clinical practice,” medical oncologist Jyoti Bajpai, DM, of Tata Memorial Cancer Centre, Mumbai, India, explained at the San Antonio Breast Cancer Symposium.

She and her colleagues had a simple idea: Reduce the dose to 2.5 mg instead of 10 mg to prevent the problem. In a randomized trial with 267 patients that Dr. Bajpai presented at the meeting, they found that the lower dose was just as effective for nausea and vomiting prophylaxis, and it greatly reduced daytime somnolence.

“This merits consideration as an antiemetic regimen of choice for highly emetogenic chemotherapy.” The findings are “practice changing,” Dr. Bajpai, the lead investigator, said.

Laura Huppert, MD, a breast oncologist at the University of California, San Francisco, wasn’t surprised by the finding.

She said she and her colleagues at UCSF use a lot of olanzapine for nausea and vomiting prophylaxis. Like the team in India, they have found that 2.5 mg is effective and causes far less sleepiness. Some patients require 5 mg, but the full 10-mg dose is rarely needed.

Although the approach is familiar at UCSF, Dr. Huppert said she doesn’t think a lot of oncologists outside of academic centers know that olanzapine is “really helpful” and that “you don’t need a high dose.” It’s “a very good clinical pearl” and “definitely a new message for some,” she said in an interview.

Over 90% of the subjects in the study were women with breast cancer. Other cancers included sarcoma, germ cell tumors, and head and neck cancer. Subjects were scheduled for their first chemotherapy session with anthracycline-cyclophosphamide and high-dose cisplatin.

The trial randomized 135 patients to 10 mg of olanzapine and 132 to 2.5mg for 5 days, starting the day of their session. They were also on standard triple-antiemetic therapy (selective serotonin receptor (5-HT3) antagonist, neurokinin-1 receptor antagonist, and single-dose dexamethasone).

There were no significant differences between the two arms regarding nausea and vomiting, which patients tracked in daily journals using symptom severity and visual analog scales.

For instance, 44.7% in the 2.5-mg arm and 43.7% in the 10-mg arm reported no vomiting, no use of rescue medications, and no or only mild nausea (P = .87). Results were similar in the first 24 hours as well as on subsequent days.

There was also no difference in the proportion of patients who did have an emetic episode or needed rescue medication: 49.2% in the 2.5-mg arm versus 48.9% with 10 mg (P = .954).

Where the two groups split was on the incidence of daytime somnolence, which was reported by 65.2% of patients in the low-dose arm but 89.6% in the standard-dose group (P < .001). During the first 24 hours, 4.5% of low-dose patients reported severe somnolence versus 40% with 10-mg dosing (P < .001).

The overall incidence declined over the remaining study days, but the differences between the two groups were comparable. On day 5, for instance, 0.8% of low-dose patients but 8.1% of standard-dose patients reported severe somnolence (P = .004).

Low-dose patients also reported less appetite suppression.

The work was supported by the Progressive Ladies Welfare Association. Dr. Bajpai didn’t have any disclosures. Dr. Huppert is an adviser for AstraZeneca.

SAN ANTONIO — The antibody-drug conjugate trastuzumab emtansine (T-DM1) does not improve survival outcomes compared with the standard of care in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.

Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.

However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life. 

Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.

Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.

Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.

Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.

At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).

There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).

However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.

Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.

The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).

Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.

Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.

Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.

“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said. 

The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — The antibody-drug conjugate trastuzumab emtansine (T-DM1) does not improve survival outcomes compared with the standard of care in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.

Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.

However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life. 

Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.

Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.

Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.

Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.

At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).

There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).

However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.

Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.

The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).

Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.

Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.

Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.

“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said. 

The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — The antibody-drug conjugate trastuzumab emtansine (T-DM1) does not improve survival outcomes compared with the standard of care in older patients with advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer, although toxicity is much lower, results from the HERB TEA study show.

Overall, the standard-of-care triple regimen of monoclonal antibodies pertuzumab and trastuzumab plus docetaxel remains the “first-line treatment for HER2-positive advanced breast cancer, regardless of age,” said study author Akihiko Shimomura, MD, PhD, who presented the findings (abstract RF02-04) on December 7 at the San Antonio Breast Cancer Symposium.

However, he noted that the standard-of-care regimen appears to be “intolerable mentally and physically” in those older than 65 years, and “impairs” quality of life. 

Therefore a “new standard treatment with less toxicity and noninferior efficacy for older patients is needed,” said Dr. Shimomura, Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo.

Dr. Shimomura and colleagues recruited patients aged 65 years or older with advanced HER2+ breast cancer who had received no prior chemotherapy for metastatic breast cancer and had a good performance status.

Patients were randomly assigned to either pertuzumab and trastuzumab plus docetaxel or T-DM1 until disease progression. The planned sample size was 250 patients, but the study was terminated after 148 participants were recruited because an interim analysis showed that T-DM1 failed to show noninferiority.

Among 75 patients assigned to the standard-of-care regimen, the mean age was 71 years, with 64% aged 65-74 years. Sixty-five percent had stage IV disease, and 35% had relapsed. These baseline characteristics were similar among the 73 patients given T-DM1.

At the data cutoff of June 15, 2023, the median progression-free survival was comparable between the two groups, at 15.6 months with the triple therapy vs 11.3 months with T-DM1 (hazard ratio [HR], 1.358; P =.1236).

There was also no significant difference in overall survival between the two groups (HR, 1.263; P =.95322).

However, T-DM1 failed to meet its primary endpoint of noninferiority to pertuzumab and trastuzumab plus docetaxel, defined as a hazard ratio for overall survival of 1.35.

Nevertheless, T-DM1 was associated with significantly less toxicity than the standard-of care-regimen, with rates of grade 3 or worse adverse events of 36.1% vs 56.8%, Shimomura reported.

The most common hematologic adverse events with the triple therapy were leukopenia (34.2%) and neutropenia (52.0%), whereas thrombocytopenia was the most common event with T-DM1 (16.7%).

Liver toxicities were also increased with the antibody-drug conjugate, whereas fatigue, diarrhea, and appetite loss were more frequently seen with the standard-of-care regimen.

Although T-DM1 did not achieve noninferiority, given its lower toxicity profile, a “detailed analysis, including geriatric assessment, is needed to identify the patient population for whom T-DM1 may be used as first line treatment,” said Shimomura.

Virginia Kaklamani, MD, codirector of the SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, said in an interview that the trial shows T-DM1 could be “a good alternative to our first line therapy in HER2+ metastatic breast cancer” for some patients.

“It is, however, unlikely to change the standard of care due to several changes in the field including the results from the KATHERINE trial and the DESTINY-Breast trials,” she said. 

The study was funded by the Japanese National Cancer Center. Dr. Shimomura declares relationships with Daiichi Sankyo, Pfizer, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., MSD Co. Ltd, Eisai Co. Ltd, Gilead Sciences, and Taiho Pharmaceutical Co. Ltd.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — New research provides some reassuring news for young women hoping to become pregnant after a diagnosis of BRCA-mutated breast cancer.

As with other breast cancers, we can now say to BRCA carriers: “Don’t worry. You can get pregnant. You’ll be okay,” said Jame Abraham, MD, chair of Hematology & Medical Oncology at the Cleveland Clinic, who was not involved in the research. 

The analysis, presented at the San Antonio Breast Cancer Symposium, revealed no issue with women becoming pregnant and carrying a healthy baby to term and reported no sign of worse disease outcomes among BRCA carriers following diagnosis and treatment. 

“The final and most important conclusion from our study is that conceiving after proper breast cancer treatment and follow-up should not be contraindicated anymore in young BRCA carriers,” a message of particular importance for oncofertility counseling, lead investigator Matteo Lambertini, MD, a breast cancer oncologist at the University of Genova, Italy, said during his SABCS presentation. 

The study was published December 7 in JAMA to coincide with his presentation.

Although pregnancy after breast cancer is generally considered safe, limited data exist for BRCA carriers in particular, Dr. Lambertini said.

The current analysis represents the largest look into the matter to date. The study included 4732 young women from across the globe who had been diagnosed with stage I-III invasive breast cancer. These women, all BRCA carriers, were 40 years or younger (median age at diagnosis, 35 years).

The team compared outcomes between 659 patients who had at least one pregnancy over a median follow-up of almost 8 years with 4073 women who did not become pregnant. 

Dr. Lambertini and colleagues reported a median time of 3.5 years from breast cancer diagnosis to conception. Overall, about 1 in 5 young BRCA carriers (22%) conceived within 10 years after their breast cancer diagnosis. Of the 80% of patients with a completed pregnancy, 91% delivered at term and only 4 infants (0.9%) had documented congenital anomalies.

In short, “the rate of pregnancy, fetal, and obstetric complications was low and in line with the expectations in a population of women with similar age and no history of breast cancer,” Dr. Lambertini said. The team cautioned, however, that the data was extracted from oncology medical records, which might have underreported maternal and fetal outcomes. 

Disease-free survival was similar among women who became pregnant and those who did not after breast cancer (adjusted HR, 0.99; 95% CI, 0.81-1.20). 

When looking at the specific BRCA gene, differences did emerge. BRCA1 carriers had better disease-free survival after pregnancy (aHR, 0.80), while BRCA2 carriers appeared to have worse disease-free survival after pregnancy (aHR, 1.55). 

For reasons that remain unclear, the researchers also found that BRCA1 carriers who got pregnant had significantly better breast cancer-specific survival (aHR, 0.59; P < .01) and overall survival (aHR, 0.58; P < .01). These women tended to have HR-negative breast cancer, which the authors also found was associated with improved survival after pregnancy (aHR, 0.76).

It’s possible, the team posited, that hormone receptor status played a role in the observed survival benefit. It’s also possible that these women were healthier overall. 

The overall survival advantage, however, did not extend to BRCA2 carriers, who tended to have hormone receptor-positive disease. Hormone receptor-positive status did not appear to have a significant impact on survival (aHR, 1.30; 95% CI, 0.95-1.76).

“While the results appear reassuring for BRCA1 carriers, more caution is needed to counsel BRCA2 carriers, “ the investigators wrote.

The study was funded by the Italian Association for Cancer Research, Gilead, and others. Investigators had numerous ties to industry, including Dr. Lambertini, who is an adviser and speaker for Roche, Pfizer, Novartis, and others. The full list of disclosures can be found with the original article.

A version of this article appeared on Medscape.com.

SAN ANTONIO — New research provides some reassuring news for young women hoping to become pregnant after a diagnosis of BRCA-mutated breast cancer.

As with other breast cancers, we can now say to BRCA carriers: “Don’t worry. You can get pregnant. You’ll be okay,” said Jame Abraham, MD, chair of Hematology & Medical Oncology at the Cleveland Clinic, who was not involved in the research. 

The analysis, presented at the San Antonio Breast Cancer Symposium, revealed no issue with women becoming pregnant and carrying a healthy baby to term and reported no sign of worse disease outcomes among BRCA carriers following diagnosis and treatment. 

“The final and most important conclusion from our study is that conceiving after proper breast cancer treatment and follow-up should not be contraindicated anymore in young BRCA carriers,” a message of particular importance for oncofertility counseling, lead investigator Matteo Lambertini, MD, a breast cancer oncologist at the University of Genova, Italy, said during his SABCS presentation. 

The study was published December 7 in JAMA to coincide with his presentation.

Although pregnancy after breast cancer is generally considered safe, limited data exist for BRCA carriers in particular, Dr. Lambertini said.

The current analysis represents the largest look into the matter to date. The study included 4732 young women from across the globe who had been diagnosed with stage I-III invasive breast cancer. These women, all BRCA carriers, were 40 years or younger (median age at diagnosis, 35 years).

The team compared outcomes between 659 patients who had at least one pregnancy over a median follow-up of almost 8 years with 4073 women who did not become pregnant. 

Dr. Lambertini and colleagues reported a median time of 3.5 years from breast cancer diagnosis to conception. Overall, about 1 in 5 young BRCA carriers (22%) conceived within 10 years after their breast cancer diagnosis. Of the 80% of patients with a completed pregnancy, 91% delivered at term and only 4 infants (0.9%) had documented congenital anomalies.

In short, “the rate of pregnancy, fetal, and obstetric complications was low and in line with the expectations in a population of women with similar age and no history of breast cancer,” Dr. Lambertini said. The team cautioned, however, that the data was extracted from oncology medical records, which might have underreported maternal and fetal outcomes. 

Disease-free survival was similar among women who became pregnant and those who did not after breast cancer (adjusted HR, 0.99; 95% CI, 0.81-1.20). 

When looking at the specific BRCA gene, differences did emerge. BRCA1 carriers had better disease-free survival after pregnancy (aHR, 0.80), while BRCA2 carriers appeared to have worse disease-free survival after pregnancy (aHR, 1.55). 

For reasons that remain unclear, the researchers also found that BRCA1 carriers who got pregnant had significantly better breast cancer-specific survival (aHR, 0.59; P < .01) and overall survival (aHR, 0.58; P < .01). These women tended to have HR-negative breast cancer, which the authors also found was associated with improved survival after pregnancy (aHR, 0.76).

It’s possible, the team posited, that hormone receptor status played a role in the observed survival benefit. It’s also possible that these women were healthier overall. 

The overall survival advantage, however, did not extend to BRCA2 carriers, who tended to have hormone receptor-positive disease. Hormone receptor-positive status did not appear to have a significant impact on survival (aHR, 1.30; 95% CI, 0.95-1.76).

“While the results appear reassuring for BRCA1 carriers, more caution is needed to counsel BRCA2 carriers, “ the investigators wrote.

The study was funded by the Italian Association for Cancer Research, Gilead, and others. Investigators had numerous ties to industry, including Dr. Lambertini, who is an adviser and speaker for Roche, Pfizer, Novartis, and others. The full list of disclosures can be found with the original article.

A version of this article appeared on Medscape.com.

SAN ANTONIO — New research provides some reassuring news for young women hoping to become pregnant after a diagnosis of BRCA-mutated breast cancer.

As with other breast cancers, we can now say to BRCA carriers: “Don’t worry. You can get pregnant. You’ll be okay,” said Jame Abraham, MD, chair of Hematology & Medical Oncology at the Cleveland Clinic, who was not involved in the research. 

The analysis, presented at the San Antonio Breast Cancer Symposium, revealed no issue with women becoming pregnant and carrying a healthy baby to term and reported no sign of worse disease outcomes among BRCA carriers following diagnosis and treatment. 

“The final and most important conclusion from our study is that conceiving after proper breast cancer treatment and follow-up should not be contraindicated anymore in young BRCA carriers,” a message of particular importance for oncofertility counseling, lead investigator Matteo Lambertini, MD, a breast cancer oncologist at the University of Genova, Italy, said during his SABCS presentation. 

The study was published December 7 in JAMA to coincide with his presentation.

Although pregnancy after breast cancer is generally considered safe, limited data exist for BRCA carriers in particular, Dr. Lambertini said.

The current analysis represents the largest look into the matter to date. The study included 4732 young women from across the globe who had been diagnosed with stage I-III invasive breast cancer. These women, all BRCA carriers, were 40 years or younger (median age at diagnosis, 35 years).

The team compared outcomes between 659 patients who had at least one pregnancy over a median follow-up of almost 8 years with 4073 women who did not become pregnant. 

Dr. Lambertini and colleagues reported a median time of 3.5 years from breast cancer diagnosis to conception. Overall, about 1 in 5 young BRCA carriers (22%) conceived within 10 years after their breast cancer diagnosis. Of the 80% of patients with a completed pregnancy, 91% delivered at term and only 4 infants (0.9%) had documented congenital anomalies.

In short, “the rate of pregnancy, fetal, and obstetric complications was low and in line with the expectations in a population of women with similar age and no history of breast cancer,” Dr. Lambertini said. The team cautioned, however, that the data was extracted from oncology medical records, which might have underreported maternal and fetal outcomes. 

Disease-free survival was similar among women who became pregnant and those who did not after breast cancer (adjusted HR, 0.99; 95% CI, 0.81-1.20). 

When looking at the specific BRCA gene, differences did emerge. BRCA1 carriers had better disease-free survival after pregnancy (aHR, 0.80), while BRCA2 carriers appeared to have worse disease-free survival after pregnancy (aHR, 1.55). 

For reasons that remain unclear, the researchers also found that BRCA1 carriers who got pregnant had significantly better breast cancer-specific survival (aHR, 0.59; P < .01) and overall survival (aHR, 0.58; P < .01). These women tended to have HR-negative breast cancer, which the authors also found was associated with improved survival after pregnancy (aHR, 0.76).

It’s possible, the team posited, that hormone receptor status played a role in the observed survival benefit. It’s also possible that these women were healthier overall. 

The overall survival advantage, however, did not extend to BRCA2 carriers, who tended to have hormone receptor-positive disease. Hormone receptor-positive status did not appear to have a significant impact on survival (aHR, 1.30; 95% CI, 0.95-1.76).

“While the results appear reassuring for BRCA1 carriers, more caution is needed to counsel BRCA2 carriers, “ the investigators wrote.

The study was funded by the Italian Association for Cancer Research, Gilead, and others. Investigators had numerous ties to industry, including Dr. Lambertini, who is an adviser and speaker for Roche, Pfizer, Novartis, and others. The full list of disclosures can be found with the original article.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Fertility preservation and/or assisted reproductive technologies do not increase the risk for short-term cancer recurrence in young women with early hormone receptor (HR)-positive breast cancer who pause endocrine therapy to conceive, according to new data from the POSITIVE trial.

“We believe these data are of vital importance for the oncofertility counseling of young breast cancer patients,” Hatem A. Azim Jr., MD, PhD, adjunct professor, School of Medicine and Breast Cancer Center, Monterrey Institute of Technology, Mexico, said in a presentation at the San Antonio Breast Cancer Symposium.

As reported previously by this news organization, the primary results of the POSITIVE trial showed that interrupting endocrine therapy to allow pregnancy does not increase the risk of recurrence at 41 months follow-up. 

Yet, there is concern that use of fertility preservation or assisted reproductive technology methods — especially those that entail the use of hormones — could have harmful effects on patients with HR-positive breast cancers, Dr. Azim explained. 

To investigate, Dr. Azim and colleagues did a secondary analysis of outcomes from the POSITIVE trial, focusing on resumption of menstruation and use of fertility preservation and assisted reproductive technologies. 

Among 516 women evaluated for the menstruation analysis, two thirds were aged 35 and older and a little more than half (53%) reported amenorrhea at enrollment, “which is not surprising,” Dr. Azim said. 

“What is encouraging,” he said, is that 85% of women recovered menses within 6 months and 94% within 12 months of pausing endocrine therapy.

Among 497 evaluable participants who paused endocrine therapy to attempt pregnancy, 368 (74%) became pregnant.

Looking at time to pregnancy, there was a clear association between younger age at enrollment and shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64% in women younger than age 35 years, 54% in those aged 35-39, and 38% in those age 40-42. In a multivariable model, age < 35 was the only factor independently associated with a shorter time to pregnancy. 
 

No Harmful Impact on Breast Cancer Outcomes

Turning to fertility preservation and use of assisted reproductive technologies, roughly half of the women (51%) underwent some form of fertility preservation at breast cancer diagnosis and before trial enrollment, most commonly ovarian stimulation for embryo or oocyte cryopreservation.

After enrollment, 43% of women underwent some form of assisted reproductive technology to attempt pregnancy, most commonly ovarian stimulation for in vitro fertilization (IVF) and cryopreserved embryo transfer.

In the multivariable model, cryopreserved embryo transfer was the only assisted reproductive technology significantly associated with a greater chance of becoming pregnant, more than doubling patients’ odds (odds ratio, 2.4).

“This means that at breast cancer diagnosis, we should consider cryopreservation of embryos for future use if desired,” Dr. Azim said. 

Again, age mattered. Women younger than 35 undergoing assisted reproductive technologies had a 50% higher chance of becoming pregnant compared with peers aged 35-39, and an 84% higher chance than women aged 40-42. 

Importantly, there was no apparent short-term detrimental impact of fertility preservation and/or assisted reproductive technologies on breast cancer outcomes, Dr. Azim reported. At 3 years, the breast cancer-free interval was almost identical between women who underwent ovarian stimulation for cryopreservation and those who did not (9.7% vs 8.7%).

“POSITIVE showed positive results that emphasize the importance of active oncofertility counseling with the patient starting at diagnosis,” said Hee Jeong Kim, MD, PhD, professor, Division of Breast Surgery, Asan Medical Center, Seoul, Republic of Korea, and discussant for the study. 

“These data are reassuring for our young patients with a diagnosis of breast cancer and shows that assisted reproductive technology is an option and is probably safe to do with the caveat that it needs longer follow-up,” added SABCS codirector Carlos Arteaga, MD, director, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas.

Dr. Azim has no relevant disclosures. Dr. Arteaga is a scientific adviser to Novartis, Lilly, Merck, AstraZeneca, Daiichi Sankyo, OrigiMed, Immunomedics, PUMA Biotechnology, TAIHO Oncology, Sanofi, and the Susan G. Komen Foundation. He has received grant support from Pfizer, Lilly, and Takeda. Dr. Kim reports no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Fertility preservation and/or assisted reproductive technologies do not increase the risk for short-term cancer recurrence in young women with early hormone receptor (HR)-positive breast cancer who pause endocrine therapy to conceive, according to new data from the POSITIVE trial.

“We believe these data are of vital importance for the oncofertility counseling of young breast cancer patients,” Hatem A. Azim Jr., MD, PhD, adjunct professor, School of Medicine and Breast Cancer Center, Monterrey Institute of Technology, Mexico, said in a presentation at the San Antonio Breast Cancer Symposium.

As reported previously by this news organization, the primary results of the POSITIVE trial showed that interrupting endocrine therapy to allow pregnancy does not increase the risk of recurrence at 41 months follow-up. 

Yet, there is concern that use of fertility preservation or assisted reproductive technology methods — especially those that entail the use of hormones — could have harmful effects on patients with HR-positive breast cancers, Dr. Azim explained. 

To investigate, Dr. Azim and colleagues did a secondary analysis of outcomes from the POSITIVE trial, focusing on resumption of menstruation and use of fertility preservation and assisted reproductive technologies. 

Among 516 women evaluated for the menstruation analysis, two thirds were aged 35 and older and a little more than half (53%) reported amenorrhea at enrollment, “which is not surprising,” Dr. Azim said. 

“What is encouraging,” he said, is that 85% of women recovered menses within 6 months and 94% within 12 months of pausing endocrine therapy.

Among 497 evaluable participants who paused endocrine therapy to attempt pregnancy, 368 (74%) became pregnant.

Looking at time to pregnancy, there was a clear association between younger age at enrollment and shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64% in women younger than age 35 years, 54% in those aged 35-39, and 38% in those age 40-42. In a multivariable model, age < 35 was the only factor independently associated with a shorter time to pregnancy. 
 

No Harmful Impact on Breast Cancer Outcomes

Turning to fertility preservation and use of assisted reproductive technologies, roughly half of the women (51%) underwent some form of fertility preservation at breast cancer diagnosis and before trial enrollment, most commonly ovarian stimulation for embryo or oocyte cryopreservation.

After enrollment, 43% of women underwent some form of assisted reproductive technology to attempt pregnancy, most commonly ovarian stimulation for in vitro fertilization (IVF) and cryopreserved embryo transfer.

In the multivariable model, cryopreserved embryo transfer was the only assisted reproductive technology significantly associated with a greater chance of becoming pregnant, more than doubling patients’ odds (odds ratio, 2.4).

“This means that at breast cancer diagnosis, we should consider cryopreservation of embryos for future use if desired,” Dr. Azim said. 

Again, age mattered. Women younger than 35 undergoing assisted reproductive technologies had a 50% higher chance of becoming pregnant compared with peers aged 35-39, and an 84% higher chance than women aged 40-42. 

Importantly, there was no apparent short-term detrimental impact of fertility preservation and/or assisted reproductive technologies on breast cancer outcomes, Dr. Azim reported. At 3 years, the breast cancer-free interval was almost identical between women who underwent ovarian stimulation for cryopreservation and those who did not (9.7% vs 8.7%).

“POSITIVE showed positive results that emphasize the importance of active oncofertility counseling with the patient starting at diagnosis,” said Hee Jeong Kim, MD, PhD, professor, Division of Breast Surgery, Asan Medical Center, Seoul, Republic of Korea, and discussant for the study. 

“These data are reassuring for our young patients with a diagnosis of breast cancer and shows that assisted reproductive technology is an option and is probably safe to do with the caveat that it needs longer follow-up,” added SABCS codirector Carlos Arteaga, MD, director, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas.

Dr. Azim has no relevant disclosures. Dr. Arteaga is a scientific adviser to Novartis, Lilly, Merck, AstraZeneca, Daiichi Sankyo, OrigiMed, Immunomedics, PUMA Biotechnology, TAIHO Oncology, Sanofi, and the Susan G. Komen Foundation. He has received grant support from Pfizer, Lilly, and Takeda. Dr. Kim reports no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Fertility preservation and/or assisted reproductive technologies do not increase the risk for short-term cancer recurrence in young women with early hormone receptor (HR)-positive breast cancer who pause endocrine therapy to conceive, according to new data from the POSITIVE trial.

“We believe these data are of vital importance for the oncofertility counseling of young breast cancer patients,” Hatem A. Azim Jr., MD, PhD, adjunct professor, School of Medicine and Breast Cancer Center, Monterrey Institute of Technology, Mexico, said in a presentation at the San Antonio Breast Cancer Symposium.

As reported previously by this news organization, the primary results of the POSITIVE trial showed that interrupting endocrine therapy to allow pregnancy does not increase the risk of recurrence at 41 months follow-up. 

Yet, there is concern that use of fertility preservation or assisted reproductive technology methods — especially those that entail the use of hormones — could have harmful effects on patients with HR-positive breast cancers, Dr. Azim explained. 

To investigate, Dr. Azim and colleagues did a secondary analysis of outcomes from the POSITIVE trial, focusing on resumption of menstruation and use of fertility preservation and assisted reproductive technologies. 

Among 516 women evaluated for the menstruation analysis, two thirds were aged 35 and older and a little more than half (53%) reported amenorrhea at enrollment, “which is not surprising,” Dr. Azim said. 

“What is encouraging,” he said, is that 85% of women recovered menses within 6 months and 94% within 12 months of pausing endocrine therapy.

Among 497 evaluable participants who paused endocrine therapy to attempt pregnancy, 368 (74%) became pregnant.

Looking at time to pregnancy, there was a clear association between younger age at enrollment and shorter time to pregnancy. The cumulative incidence of pregnancy at 12 months was 64% in women younger than age 35 years, 54% in those aged 35-39, and 38% in those age 40-42. In a multivariable model, age < 35 was the only factor independently associated with a shorter time to pregnancy. 
 

No Harmful Impact on Breast Cancer Outcomes

Turning to fertility preservation and use of assisted reproductive technologies, roughly half of the women (51%) underwent some form of fertility preservation at breast cancer diagnosis and before trial enrollment, most commonly ovarian stimulation for embryo or oocyte cryopreservation.

After enrollment, 43% of women underwent some form of assisted reproductive technology to attempt pregnancy, most commonly ovarian stimulation for in vitro fertilization (IVF) and cryopreserved embryo transfer.

In the multivariable model, cryopreserved embryo transfer was the only assisted reproductive technology significantly associated with a greater chance of becoming pregnant, more than doubling patients’ odds (odds ratio, 2.4).

“This means that at breast cancer diagnosis, we should consider cryopreservation of embryos for future use if desired,” Dr. Azim said. 

Again, age mattered. Women younger than 35 undergoing assisted reproductive technologies had a 50% higher chance of becoming pregnant compared with peers aged 35-39, and an 84% higher chance than women aged 40-42. 

Importantly, there was no apparent short-term detrimental impact of fertility preservation and/or assisted reproductive technologies on breast cancer outcomes, Dr. Azim reported. At 3 years, the breast cancer-free interval was almost identical between women who underwent ovarian stimulation for cryopreservation and those who did not (9.7% vs 8.7%).

“POSITIVE showed positive results that emphasize the importance of active oncofertility counseling with the patient starting at diagnosis,” said Hee Jeong Kim, MD, PhD, professor, Division of Breast Surgery, Asan Medical Center, Seoul, Republic of Korea, and discussant for the study. 

“These data are reassuring for our young patients with a diagnosis of breast cancer and shows that assisted reproductive technology is an option and is probably safe to do with the caveat that it needs longer follow-up,” added SABCS codirector Carlos Arteaga, MD, director, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas.

Dr. Azim has no relevant disclosures. Dr. Arteaga is a scientific adviser to Novartis, Lilly, Merck, AstraZeneca, Daiichi Sankyo, OrigiMed, Immunomedics, PUMA Biotechnology, TAIHO Oncology, Sanofi, and the Susan G. Komen Foundation. He has received grant support from Pfizer, Lilly, and Takeda. Dr. Kim reports no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Women with early breast cancer who have less extensive axillary surgery see no effect on their 10-year rates of locoregional recurrence and mortality than do those who have more extensive surgery, according to findings from a large meta-analysis.

Less extensive surgery also reduced patients’ risk for lymphedema, according to research (abstract GS02-05) presented at the San Antonio Breast Cancer Symposium.

These results, which included data from more than 20,000 women, may “reassure” patients and clinicians that more extensive axillary lymph node dissection “does not improve outcomes in many women with early-stage breast cancer,” said Andrea V. Barrio, MD, a breast surgeon at Memorial Sloan Kettering Cancer Center, New York City, who was not involved in the study.

Gurdeep S. Mannu, DPhil, of the University of Oxford, United Kingdom, who presented the findings at SABCS, explained that the optimal surgical management of the axilla remains uncertain in this patient population. 

To better understand the long-term risks and benefits of more vs less aggressive axillary surgery in early breast cancer, Dr. Mannu and colleagues performed a meta-analysis of 29 randomized trials conducted over six decades, which included data on 20,285 women. The trials compared more vs less extensive axillary surgery as well as axillary surgery vs axillary radiotherapy.

In trials comparing more vs less extensive axillary surgery, researchers found that 83% of locoregional recurrences occurred in the breast or in multiple sites/unspecified locations, and the remaining 17% occurred in isolated axilla or other local recurrences, such as in the supraclavicular fossa or internal mammary chain. 

Those with recurrences in the breast or multiple sites/unspecified locations did not benefit from more extensive surgery, demonstrating similar recurrence rates (RR) (RR for breast, 1.13; 95% CI, 0.92-1.40; RR for other, 0.89; 95% CI, 0.67-1.18).

The group with recurrences in isolated axilla or other local recurrences tended to do better with more extensive surgery (RR, 0.43 and 0.41, respectively).

Overall though, after a median follow-up of 10 years, differences in locoregional recurrence rates at any site did not differ among patients who had more vs less extensive axillary surgery (RR, 0.91; P = .22). This finding held even when restricting the analysis to women with node-positive disease/unknown nodal status (RR, 1.00; P = .98) and for node-negative women (RR, 0.88; P = .15).

Dr. Mannu and colleagues observed similar findings for distant recurrence, breast cancer mortality, and death from any cause.

“But where there was quite a striking difference was in morbidity,” said Dr. Mannu.

To examine rates of lymphedema — the surgical complication that has been “one of the main motivations” for the deescalation trials of the past few decades — the researchers focused on more recent trials, which “are most relevant to women treated today,” Dr. Mannu explained. 

These showed that more extensive axillary surgery was associated with almost 2.5-times the rate of lymphedema compared with less extensive treatment (odds ratio [OR], 2.43).

Finally, the team compared axillary dissection with axillary radiotherapy across five trials and found no significant differences in the treatment approaches in terms of locoregional occurrence, distant recurrence, breast cancer mortality, and death from any cause.

However, once again, a notable difference in rates of lymphedema occurred, with axillary dissection associated with higher rates compared with radiotherapy (OR, 1.79).

This is “probably the largest meta-analysis comparing more vs less axillary surgery,” Dr. Barrio said in an interview. 

“When we have one or two positive sentinel nodes, anywhere from 30%-50% of women will have additional positive lymph nodes that we’re not removing” with less extensive surgery, she explained. This study shows that, even then, this “doesn’t seem to impact on survival.”

This is “likely related to better medical treatment and radiation techniques that can treat that disease just as well as big surgery, but with less lymphedema,” she added. 

Nevertheless, Dr. Barrio believes that there are “situations where we still feel that axillary lymph node dissection is important: in women with advanced cancer, like inflammatory breast cancer, and in women who’ve received chemotherapy upfront, then had surgery, and still have positive nodes after the chemo.”

The study was funded by Cancer Research UK, British Heart Foundation, Medical Research Council.

No relevant financial relationships have been declared.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Women with early breast cancer who have less extensive axillary surgery see no effect on their 10-year rates of locoregional recurrence and mortality than do those who have more extensive surgery, according to findings from a large meta-analysis.

Less extensive surgery also reduced patients’ risk for lymphedema, according to research (abstract GS02-05) presented at the San Antonio Breast Cancer Symposium.

These results, which included data from more than 20,000 women, may “reassure” patients and clinicians that more extensive axillary lymph node dissection “does not improve outcomes in many women with early-stage breast cancer,” said Andrea V. Barrio, MD, a breast surgeon at Memorial Sloan Kettering Cancer Center, New York City, who was not involved in the study.

Gurdeep S. Mannu, DPhil, of the University of Oxford, United Kingdom, who presented the findings at SABCS, explained that the optimal surgical management of the axilla remains uncertain in this patient population. 

To better understand the long-term risks and benefits of more vs less aggressive axillary surgery in early breast cancer, Dr. Mannu and colleagues performed a meta-analysis of 29 randomized trials conducted over six decades, which included data on 20,285 women. The trials compared more vs less extensive axillary surgery as well as axillary surgery vs axillary radiotherapy.

In trials comparing more vs less extensive axillary surgery, researchers found that 83% of locoregional recurrences occurred in the breast or in multiple sites/unspecified locations, and the remaining 17% occurred in isolated axilla or other local recurrences, such as in the supraclavicular fossa or internal mammary chain. 

Those with recurrences in the breast or multiple sites/unspecified locations did not benefit from more extensive surgery, demonstrating similar recurrence rates (RR) (RR for breast, 1.13; 95% CI, 0.92-1.40; RR for other, 0.89; 95% CI, 0.67-1.18).

The group with recurrences in isolated axilla or other local recurrences tended to do better with more extensive surgery (RR, 0.43 and 0.41, respectively).

Overall though, after a median follow-up of 10 years, differences in locoregional recurrence rates at any site did not differ among patients who had more vs less extensive axillary surgery (RR, 0.91; P = .22). This finding held even when restricting the analysis to women with node-positive disease/unknown nodal status (RR, 1.00; P = .98) and for node-negative women (RR, 0.88; P = .15).

Dr. Mannu and colleagues observed similar findings for distant recurrence, breast cancer mortality, and death from any cause.

“But where there was quite a striking difference was in morbidity,” said Dr. Mannu.

To examine rates of lymphedema — the surgical complication that has been “one of the main motivations” for the deescalation trials of the past few decades — the researchers focused on more recent trials, which “are most relevant to women treated today,” Dr. Mannu explained. 

These showed that more extensive axillary surgery was associated with almost 2.5-times the rate of lymphedema compared with less extensive treatment (odds ratio [OR], 2.43).

Finally, the team compared axillary dissection with axillary radiotherapy across five trials and found no significant differences in the treatment approaches in terms of locoregional occurrence, distant recurrence, breast cancer mortality, and death from any cause.

However, once again, a notable difference in rates of lymphedema occurred, with axillary dissection associated with higher rates compared with radiotherapy (OR, 1.79).

This is “probably the largest meta-analysis comparing more vs less axillary surgery,” Dr. Barrio said in an interview. 

“When we have one or two positive sentinel nodes, anywhere from 30%-50% of women will have additional positive lymph nodes that we’re not removing” with less extensive surgery, she explained. This study shows that, even then, this “doesn’t seem to impact on survival.”

This is “likely related to better medical treatment and radiation techniques that can treat that disease just as well as big surgery, but with less lymphedema,” she added. 

Nevertheless, Dr. Barrio believes that there are “situations where we still feel that axillary lymph node dissection is important: in women with advanced cancer, like inflammatory breast cancer, and in women who’ve received chemotherapy upfront, then had surgery, and still have positive nodes after the chemo.”

The study was funded by Cancer Research UK, British Heart Foundation, Medical Research Council.

No relevant financial relationships have been declared.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Women with early breast cancer who have less extensive axillary surgery see no effect on their 10-year rates of locoregional recurrence and mortality than do those who have more extensive surgery, according to findings from a large meta-analysis.

Less extensive surgery also reduced patients’ risk for lymphedema, according to research (abstract GS02-05) presented at the San Antonio Breast Cancer Symposium.

These results, which included data from more than 20,000 women, may “reassure” patients and clinicians that more extensive axillary lymph node dissection “does not improve outcomes in many women with early-stage breast cancer,” said Andrea V. Barrio, MD, a breast surgeon at Memorial Sloan Kettering Cancer Center, New York City, who was not involved in the study.

Gurdeep S. Mannu, DPhil, of the University of Oxford, United Kingdom, who presented the findings at SABCS, explained that the optimal surgical management of the axilla remains uncertain in this patient population. 

To better understand the long-term risks and benefits of more vs less aggressive axillary surgery in early breast cancer, Dr. Mannu and colleagues performed a meta-analysis of 29 randomized trials conducted over six decades, which included data on 20,285 women. The trials compared more vs less extensive axillary surgery as well as axillary surgery vs axillary radiotherapy.

In trials comparing more vs less extensive axillary surgery, researchers found that 83% of locoregional recurrences occurred in the breast or in multiple sites/unspecified locations, and the remaining 17% occurred in isolated axilla or other local recurrences, such as in the supraclavicular fossa or internal mammary chain. 

Those with recurrences in the breast or multiple sites/unspecified locations did not benefit from more extensive surgery, demonstrating similar recurrence rates (RR) (RR for breast, 1.13; 95% CI, 0.92-1.40; RR for other, 0.89; 95% CI, 0.67-1.18).

The group with recurrences in isolated axilla or other local recurrences tended to do better with more extensive surgery (RR, 0.43 and 0.41, respectively).

Overall though, after a median follow-up of 10 years, differences in locoregional recurrence rates at any site did not differ among patients who had more vs less extensive axillary surgery (RR, 0.91; P = .22). This finding held even when restricting the analysis to women with node-positive disease/unknown nodal status (RR, 1.00; P = .98) and for node-negative women (RR, 0.88; P = .15).

Dr. Mannu and colleagues observed similar findings for distant recurrence, breast cancer mortality, and death from any cause.

“But where there was quite a striking difference was in morbidity,” said Dr. Mannu.

To examine rates of lymphedema — the surgical complication that has been “one of the main motivations” for the deescalation trials of the past few decades — the researchers focused on more recent trials, which “are most relevant to women treated today,” Dr. Mannu explained. 

These showed that more extensive axillary surgery was associated with almost 2.5-times the rate of lymphedema compared with less extensive treatment (odds ratio [OR], 2.43).

Finally, the team compared axillary dissection with axillary radiotherapy across five trials and found no significant differences in the treatment approaches in terms of locoregional occurrence, distant recurrence, breast cancer mortality, and death from any cause.

However, once again, a notable difference in rates of lymphedema occurred, with axillary dissection associated with higher rates compared with radiotherapy (OR, 1.79).

This is “probably the largest meta-analysis comparing more vs less axillary surgery,” Dr. Barrio said in an interview. 

“When we have one or two positive sentinel nodes, anywhere from 30%-50% of women will have additional positive lymph nodes that we’re not removing” with less extensive surgery, she explained. This study shows that, even then, this “doesn’t seem to impact on survival.”

This is “likely related to better medical treatment and radiation techniques that can treat that disease just as well as big surgery, but with less lymphedema,” she added. 

Nevertheless, Dr. Barrio believes that there are “situations where we still feel that axillary lymph node dissection is important: in women with advanced cancer, like inflammatory breast cancer, and in women who’ve received chemotherapy upfront, then had surgery, and still have positive nodes after the chemo.”

The study was funded by Cancer Research UK, British Heart Foundation, Medical Research Council.

No relevant financial relationships have been declared.

A version of this article appeared on Medscape.com.

SAN ANTONIO — Guideline-concordant care is associated with improved overall survival in patients with inflammatory breast cancer. Yet, a retrospective study of patients with inflammatory breast carcinoma shows that the majority of patients don’t receive it. 

The study also showed that overall survival was lowest for Black women who didn’t receive guideline-concordant care, said Brian Diskin, MD, with the Division of Breast Surgery, Memorial Sloan Kettering Cancer Center, New York City, here at the San Antonio Breast Cancer Symposium.

The results highlight the importance of adhering to guidelines in inflammatory breast carcinoma and suggest that improving the rates among Black patients “may help to mitigate racial disparities and survival,” Dr.Diskin told the conference. 

Inflammatory breast carcinoma is an aggressive form of breast cancer associated with worse survival outcomes compared with other subtypes of breast cancer. Yet, it’s unclear how often and consistently guideline-concordant care — defined as treatment with neoadjuvant chemotherapy followed by modified radical mastectomy without immediate reconstruction, and postmastectomy radiotherapy — is received and what factors play a role in receiving recommended care. 

To investigate, Dr. Diskin and colleagues identified 6945 women from the National Cancer Database with nonmetastatic inflammatory breast cancer treated from 2010-2018. Guideline-concordant care was defined as trimodality treatment administered in the correct sequence, with neoadjuvant chemotherapy started within 60 days of diagnosis. 

Most patients (88%) did not start neoadjuvant chemotherapy within 60 days of diagnosis. 

Black and Asian patients were less likely than were White patients to start chemotherapy within 60 days (odds ratio [OR] 0.54 and 0.51, respectively; P < .001), while patients with Medicare or private insurance were more likely to receive chemotherapy within 60 days of diagnosis than uninsured patients (OR 1.37 and 1.87, respectively; P < .001).

Roughly half of all patients didn’t receive appropriate surgical treatment (modified radical mastectomy without immediate reconstruction and postmastectomy radiotherapy). 

Overall, only about one third of the cohort received guideline-concordant treatment, Dr. Diskin reported. 

Patients aged 60-69 were more likely than were patients aged 40-49 to receive guideline-concordant treatment (odds ratio [OR], 1.24; P < .001), as were patients with a higher clinical nodal burden (OR, 1.34 for N1; OR, 1.28 for N2; OR, 1.15 for N3 vs N0; P < .001 for N1 and N2). 

Patients treated between 2014 and 2018 were less likely to receive guideline-concordant treatment than patients treated between 2010 and 2013 (OR, 0.63; P <.001). 

Receiving guideline-concordant care and being privately insured were both positively associated with improved overall survival (OR, 0.75 and 0.62, respectively; P < .001). Conversely, triple-negative subtype and Black race were associated with worse overall survival (HR, 1.6 and 1.4, respectively; P < .001). 

However, timely receipt of guideline-concordant care for Black patients with triple-negative disease did lead to improved overall survival. Among recipients of guideline-based care with triple-negative disease, there was no racial disparity in overall survival. 

Study discussant Kathryn Hudson, MD, director of survivorship and medical oncologist at Texas Oncology, Austin, said it’s important to note that Black women have a 4% lower incidence of breast cancer than do White women but a 40% higher breast cancer death rate. 

“This study is important because it confirms that those who receive guideline-based care have better outcomes and that Black women have worse survival in [inflammatory breast cancer],” Dr. Hudson said. 

The finding that Black and Asian women in the study were less likely to have timely neoadjuvant chemotherapy, “likely reflects worse access to care, and this may play a role in why Black women had worse outcomes,” she added. 

Dr. Hudson said she found it “surprising” that only about one third of patients received guideline-concordant care.

In her view, “the take-home message is that improving guideline-concordant will improve outcomes for all patients with inflammatory breast cancer. And it’s really important, as a next step, to examine the barriers to guideline-concordant care in inflammatory breast cancer and continue to understand the reasons for worse [rates of] survival of Black women.”

Dr. Diskin has disclosed no relevant financial relationships. Dr. Hudson has received honoraria from the Menarini Group and Gilead.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Guideline-concordant care is associated with improved overall survival in patients with inflammatory breast cancer. Yet, a retrospective study of patients with inflammatory breast carcinoma shows that the majority of patients don’t receive it. 

The study also showed that overall survival was lowest for Black women who didn’t receive guideline-concordant care, said Brian Diskin, MD, with the Division of Breast Surgery, Memorial Sloan Kettering Cancer Center, New York City, here at the San Antonio Breast Cancer Symposium.

The results highlight the importance of adhering to guidelines in inflammatory breast carcinoma and suggest that improving the rates among Black patients “may help to mitigate racial disparities and survival,” Dr.Diskin told the conference. 

Inflammatory breast carcinoma is an aggressive form of breast cancer associated with worse survival outcomes compared with other subtypes of breast cancer. Yet, it’s unclear how often and consistently guideline-concordant care — defined as treatment with neoadjuvant chemotherapy followed by modified radical mastectomy without immediate reconstruction, and postmastectomy radiotherapy — is received and what factors play a role in receiving recommended care. 

To investigate, Dr. Diskin and colleagues identified 6945 women from the National Cancer Database with nonmetastatic inflammatory breast cancer treated from 2010-2018. Guideline-concordant care was defined as trimodality treatment administered in the correct sequence, with neoadjuvant chemotherapy started within 60 days of diagnosis. 

Most patients (88%) did not start neoadjuvant chemotherapy within 60 days of diagnosis. 

Black and Asian patients were less likely than were White patients to start chemotherapy within 60 days (odds ratio [OR] 0.54 and 0.51, respectively; P < .001), while patients with Medicare or private insurance were more likely to receive chemotherapy within 60 days of diagnosis than uninsured patients (OR 1.37 and 1.87, respectively; P < .001).

Roughly half of all patients didn’t receive appropriate surgical treatment (modified radical mastectomy without immediate reconstruction and postmastectomy radiotherapy). 

Overall, only about one third of the cohort received guideline-concordant treatment, Dr. Diskin reported. 

Patients aged 60-69 were more likely than were patients aged 40-49 to receive guideline-concordant treatment (odds ratio [OR], 1.24; P < .001), as were patients with a higher clinical nodal burden (OR, 1.34 for N1; OR, 1.28 for N2; OR, 1.15 for N3 vs N0; P < .001 for N1 and N2). 

Patients treated between 2014 and 2018 were less likely to receive guideline-concordant treatment than patients treated between 2010 and 2013 (OR, 0.63; P <.001). 

Receiving guideline-concordant care and being privately insured were both positively associated with improved overall survival (OR, 0.75 and 0.62, respectively; P < .001). Conversely, triple-negative subtype and Black race were associated with worse overall survival (HR, 1.6 and 1.4, respectively; P < .001). 

However, timely receipt of guideline-concordant care for Black patients with triple-negative disease did lead to improved overall survival. Among recipients of guideline-based care with triple-negative disease, there was no racial disparity in overall survival. 

Study discussant Kathryn Hudson, MD, director of survivorship and medical oncologist at Texas Oncology, Austin, said it’s important to note that Black women have a 4% lower incidence of breast cancer than do White women but a 40% higher breast cancer death rate. 

“This study is important because it confirms that those who receive guideline-based care have better outcomes and that Black women have worse survival in [inflammatory breast cancer],” Dr. Hudson said. 

The finding that Black and Asian women in the study were less likely to have timely neoadjuvant chemotherapy, “likely reflects worse access to care, and this may play a role in why Black women had worse outcomes,” she added. 

Dr. Hudson said she found it “surprising” that only about one third of patients received guideline-concordant care.

In her view, “the take-home message is that improving guideline-concordant will improve outcomes for all patients with inflammatory breast cancer. And it’s really important, as a next step, to examine the barriers to guideline-concordant care in inflammatory breast cancer and continue to understand the reasons for worse [rates of] survival of Black women.”

Dr. Diskin has disclosed no relevant financial relationships. Dr. Hudson has received honoraria from the Menarini Group and Gilead.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Guideline-concordant care is associated with improved overall survival in patients with inflammatory breast cancer. Yet, a retrospective study of patients with inflammatory breast carcinoma shows that the majority of patients don’t receive it. 

The study also showed that overall survival was lowest for Black women who didn’t receive guideline-concordant care, said Brian Diskin, MD, with the Division of Breast Surgery, Memorial Sloan Kettering Cancer Center, New York City, here at the San Antonio Breast Cancer Symposium.

The results highlight the importance of adhering to guidelines in inflammatory breast carcinoma and suggest that improving the rates among Black patients “may help to mitigate racial disparities and survival,” Dr.Diskin told the conference. 

Inflammatory breast carcinoma is an aggressive form of breast cancer associated with worse survival outcomes compared with other subtypes of breast cancer. Yet, it’s unclear how often and consistently guideline-concordant care — defined as treatment with neoadjuvant chemotherapy followed by modified radical mastectomy without immediate reconstruction, and postmastectomy radiotherapy — is received and what factors play a role in receiving recommended care. 

To investigate, Dr. Diskin and colleagues identified 6945 women from the National Cancer Database with nonmetastatic inflammatory breast cancer treated from 2010-2018. Guideline-concordant care was defined as trimodality treatment administered in the correct sequence, with neoadjuvant chemotherapy started within 60 days of diagnosis. 

Most patients (88%) did not start neoadjuvant chemotherapy within 60 days of diagnosis. 

Black and Asian patients were less likely than were White patients to start chemotherapy within 60 days (odds ratio [OR] 0.54 and 0.51, respectively; P < .001), while patients with Medicare or private insurance were more likely to receive chemotherapy within 60 days of diagnosis than uninsured patients (OR 1.37 and 1.87, respectively; P < .001).

Roughly half of all patients didn’t receive appropriate surgical treatment (modified radical mastectomy without immediate reconstruction and postmastectomy radiotherapy). 

Overall, only about one third of the cohort received guideline-concordant treatment, Dr. Diskin reported. 

Patients aged 60-69 were more likely than were patients aged 40-49 to receive guideline-concordant treatment (odds ratio [OR], 1.24; P < .001), as were patients with a higher clinical nodal burden (OR, 1.34 for N1; OR, 1.28 for N2; OR, 1.15 for N3 vs N0; P < .001 for N1 and N2). 

Patients treated between 2014 and 2018 were less likely to receive guideline-concordant treatment than patients treated between 2010 and 2013 (OR, 0.63; P <.001). 

Receiving guideline-concordant care and being privately insured were both positively associated with improved overall survival (OR, 0.75 and 0.62, respectively; P < .001). Conversely, triple-negative subtype and Black race were associated with worse overall survival (HR, 1.6 and 1.4, respectively; P < .001). 

However, timely receipt of guideline-concordant care for Black patients with triple-negative disease did lead to improved overall survival. Among recipients of guideline-based care with triple-negative disease, there was no racial disparity in overall survival. 

Study discussant Kathryn Hudson, MD, director of survivorship and medical oncologist at Texas Oncology, Austin, said it’s important to note that Black women have a 4% lower incidence of breast cancer than do White women but a 40% higher breast cancer death rate. 

“This study is important because it confirms that those who receive guideline-based care have better outcomes and that Black women have worse survival in [inflammatory breast cancer],” Dr. Hudson said. 

The finding that Black and Asian women in the study were less likely to have timely neoadjuvant chemotherapy, “likely reflects worse access to care, and this may play a role in why Black women had worse outcomes,” she added. 

Dr. Hudson said she found it “surprising” that only about one third of patients received guideline-concordant care.

In her view, “the take-home message is that improving guideline-concordant will improve outcomes for all patients with inflammatory breast cancer. And it’s really important, as a next step, to examine the barriers to guideline-concordant care in inflammatory breast cancer and continue to understand the reasons for worse [rates of] survival of Black women.”

Dr. Diskin has disclosed no relevant financial relationships. Dr. Hudson has received honoraria from the Menarini Group and Gilead.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Low-dose tamoxifen, sometimes called “baby TAM,” is gaining traction as an alternative to full-dose tamoxifen for use in breast cancer prevention. The drug can reduce incidence of breast cancer in high-risk individuals, but side effects that mimic menopause have led to low rates of uptake. Lower-dose tamoxifen aims to reduce those side effects, but there remains some uncertainty about the minimum dose required to maintain efficacy.

The TAM-01 study, first published in 2019, demonstrated that a 5-mg dose of tamoxifen led to a reduction in recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS). At the San Antonio Breast Cancer Symposium, two studies were presented that provided insight into dose efficacy and likelihood of medication adherence in women taking baby TAM.

“We all know that women who are at increased risk for breast cancer may benefit from the use of tamoxifen to help lower their risk, although historical uptake to tamoxifen in the prevention setting has been quite low,” said Lauren Cornell, MD, during a presentation. Her team investigated the impact of patient counseling on how well they understood their risk, as well as their likelihood of adherence to the medication.

The study included 41 women, and 31 completed follow-up at 1 year. “We saw that 90% of our patients reported good or complete understanding of their breast cancer risk after the consultation, emphasizing the benefit of that consult, and 73% reported that the availability of baby tamoxifen helped in their decision to consider a preventative medication,” said Dr. Cornell during her presentation. After 1 year of follow-up, 74% said that they had initiated baby tamoxifen, and 78% of those who started taking the drug were still taking it at 1 year.

Participants who continued to take baby TAM at 1 year had a higher estimated breast cancer risk (IBIS 10-year risk, 12.7% vs 7.6%; P = .027) than those who discontinued. “We saw that uptake to baby TAM after informed discussion in patients who qualify is high, especially in those patients with high risk and intraepithelial lesions or DCIS, and adherence and tolerability at 1 year follow up is improved, compared to what we would expect with traditional dosing of tamoxifen. It’s important to note that the NCCN guidelines and the ASCO clinical practice update now include low-dose tamoxifen as an option for select women, and future randomized control trials on de-escalation of tamoxifen and high-risk patients based on their risk model assessment still need to be done. Future study should also focus on markers to identify candidates best suited for low versus standard dose of tamoxifen,” said Dr. Cornell, who is an assistant professor of medicine at Mayo Clinic Florida in Jacksonville.

At another SABCS session, Per Hall, MD, PhD, discussed findings from the previously published KARISMA-2 study, which examined efficacy of various doses of tamoxifen. A total of 1440 participants, 240 in each arm, received tamoxifen doses of 20 mg, 10 mg, 5 mg, 2.5 mg, 1 mg, or placebo. During his talk, Dr. Hall pointed out that measuring outcomes would take a very large number of participants to identify small differences in breast cancer rates. Therefore, the researchers examined breast density changes as a proxy. As a noninferiority outcome, the researchers used the proportion of women in each arm who achieved the median decrease in breast density seen at 20 mg of tamoxifen, which is 10.1%.

The women underwent mammograms at baseline and again at 6 months to determine change in breast density. Among all women in the study, the proportion of patients who had a similar breast density reduction as the 20-mg dose were very similar in the 10 mg (50.0%; P = .002), 5 mg (49.3%; P < .001), and 2.5 mg (52.5%; P < .001) groups. The 1 mg group had a proportion of 39.5% (P = .138), while the placebo group had 38.9% (P = .161). However, the results were driven by premenopausal women, where the values were 63.3%, 70.7%, 74.4%, and 69.7% in the 20-mg, 10-mg, 5-mg, and 2.5-mg groups, respectively, and 32.9% at 1 mg and 29.7% on placebo. In postmenopausal women, the values were 41.9%, 36.7%, 33.3%, and 41.9% in the 20-mg, 10-mg, 5-mg, and 2.5-mg groups, with values of 44.2% in the 1-mg group and 43.8% in the placebo group.

The median density change was 18.5% in premenopausal women and 4.0% in postmenopausal women.

“We didn’t see anything in the postmenopausal women. The decrease for those on 20 milligrams and those on placebo were exactly the same. Why this is, we still don’t know because we do know that tamoxifen in the adjuvant setting could be used for postmenopausal women. It could be that 6 months is too short of a time [to see a benefit]. We don’t know,” said Dr. Hall, who is a medical epidemiologist and biostatistician at Karolinska Institutet, Stockholm, Sweden.

Severe vasomotor side effects like hot flashes, cold flashes, and night sweats were reduced by about 50% in the lower tamoxifen doses, compared with 20 mg.

Dr. Hall also pointed out that tamoxifen is a prodrug. The CYP2D6 enzyme produces a range of metabolites, with endoxifen having the strongest affinity to the estrogen receptor and being present at the highest plasma concentration. He showed a table of endoxifen plasma levels at various tamoxifen doses in women of various metabolizer status, ranging from poor to ultrafast. Among intermediate, normal, and ultrarapid metabolizers, 5- and 10-mg doses produced plasma endoxifen levels ranging from 2.4 to 6.2 ng/mL, which represents a good therapeutic window. “For intermediate and normal metabolizers, it could be that 5 mg [of tamoxifen] is enough, but I want to underline that we didn’t use breast cancer incidence or recurrence in this study, we used density change, so we should be careful when we use these results,” said Dr. Hall. His group is now conducting the KARISMA Endoxifen trial, which will test endoxifen directly at doses of 1 and 2 mg.

Dr. Cornell has no relevant financial disclosures. Dr. Hall is a member of the scientific advisory board for Atossa Therapeutics.

SAN ANTONIO — Low-dose tamoxifen, sometimes called “baby TAM,” is gaining traction as an alternative to full-dose tamoxifen for use in breast cancer prevention. The drug can reduce incidence of breast cancer in high-risk individuals, but side effects that mimic menopause have led to low rates of uptake. Lower-dose tamoxifen aims to reduce those side effects, but there remains some uncertainty about the minimum dose required to maintain efficacy.

The TAM-01 study, first published in 2019, demonstrated that a 5-mg dose of tamoxifen led to a reduction in recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS). At the San Antonio Breast Cancer Symposium, two studies were presented that provided insight into dose efficacy and likelihood of medication adherence in women taking baby TAM.

“We all know that women who are at increased risk for breast cancer may benefit from the use of tamoxifen to help lower their risk, although historical uptake to tamoxifen in the prevention setting has been quite low,” said Lauren Cornell, MD, during a presentation. Her team investigated the impact of patient counseling on how well they understood their risk, as well as their likelihood of adherence to the medication.

The study included 41 women, and 31 completed follow-up at 1 year. “We saw that 90% of our patients reported good or complete understanding of their breast cancer risk after the consultation, emphasizing the benefit of that consult, and 73% reported that the availability of baby tamoxifen helped in their decision to consider a preventative medication,” said Dr. Cornell during her presentation. After 1 year of follow-up, 74% said that they had initiated baby tamoxifen, and 78% of those who started taking the drug were still taking it at 1 year.

Participants who continued to take baby TAM at 1 year had a higher estimated breast cancer risk (IBIS 10-year risk, 12.7% vs 7.6%; P = .027) than those who discontinued. “We saw that uptake to baby TAM after informed discussion in patients who qualify is high, especially in those patients with high risk and intraepithelial lesions or DCIS, and adherence and tolerability at 1 year follow up is improved, compared to what we would expect with traditional dosing of tamoxifen. It’s important to note that the NCCN guidelines and the ASCO clinical practice update now include low-dose tamoxifen as an option for select women, and future randomized control trials on de-escalation of tamoxifen and high-risk patients based on their risk model assessment still need to be done. Future study should also focus on markers to identify candidates best suited for low versus standard dose of tamoxifen,” said Dr. Cornell, who is an assistant professor of medicine at Mayo Clinic Florida in Jacksonville.

At another SABCS session, Per Hall, MD, PhD, discussed findings from the previously published KARISMA-2 study, which examined efficacy of various doses of tamoxifen. A total of 1440 participants, 240 in each arm, received tamoxifen doses of 20 mg, 10 mg, 5 mg, 2.5 mg, 1 mg, or placebo. During his talk, Dr. Hall pointed out that measuring outcomes would take a very large number of participants to identify small differences in breast cancer rates. Therefore, the researchers examined breast density changes as a proxy. As a noninferiority outcome, the researchers used the proportion of women in each arm who achieved the median decrease in breast density seen at 20 mg of tamoxifen, which is 10.1%.

The women underwent mammograms at baseline and again at 6 months to determine change in breast density. Among all women in the study, the proportion of patients who had a similar breast density reduction as the 20-mg dose were very similar in the 10 mg (50.0%; P = .002), 5 mg (49.3%; P < .001), and 2.5 mg (52.5%; P < .001) groups. The 1 mg group had a proportion of 39.5% (P = .138), while the placebo group had 38.9% (P = .161). However, the results were driven by premenopausal women, where the values were 63.3%, 70.7%, 74.4%, and 69.7% in the 20-mg, 10-mg, 5-mg, and 2.5-mg groups, respectively, and 32.9% at 1 mg and 29.7% on placebo. In postmenopausal women, the values were 41.9%, 36.7%, 33.3%, and 41.9% in the 20-mg, 10-mg, 5-mg, and 2.5-mg groups, with values of 44.2% in the 1-mg group and 43.8% in the placebo group.

The median density change was 18.5% in premenopausal women and 4.0% in postmenopausal women.

“We didn’t see anything in the postmenopausal women. The decrease for those on 20 milligrams and those on placebo were exactly the same. Why this is, we still don’t know because we do know that tamoxifen in the adjuvant setting could be used for postmenopausal women. It could be that 6 months is too short of a time [to see a benefit]. We don’t know,” said Dr. Hall, who is a medical epidemiologist and biostatistician at Karolinska Institutet, Stockholm, Sweden.

Severe vasomotor side effects like hot flashes, cold flashes, and night sweats were reduced by about 50% in the lower tamoxifen doses, compared with 20 mg.

Dr. Hall also pointed out that tamoxifen is a prodrug. The CYP2D6 enzyme produces a range of metabolites, with endoxifen having the strongest affinity to the estrogen receptor and being present at the highest plasma concentration. He showed a table of endoxifen plasma levels at various tamoxifen doses in women of various metabolizer status, ranging from poor to ultrafast. Among intermediate, normal, and ultrarapid metabolizers, 5- and 10-mg doses produced plasma endoxifen levels ranging from 2.4 to 6.2 ng/mL, which represents a good therapeutic window. “For intermediate and normal metabolizers, it could be that 5 mg [of tamoxifen] is enough, but I want to underline that we didn’t use breast cancer incidence or recurrence in this study, we used density change, so we should be careful when we use these results,” said Dr. Hall. His group is now conducting the KARISMA Endoxifen trial, which will test endoxifen directly at doses of 1 and 2 mg.

Dr. Cornell has no relevant financial disclosures. Dr. Hall is a member of the scientific advisory board for Atossa Therapeutics.

SAN ANTONIO — Low-dose tamoxifen, sometimes called “baby TAM,” is gaining traction as an alternative to full-dose tamoxifen for use in breast cancer prevention. The drug can reduce incidence of breast cancer in high-risk individuals, but side effects that mimic menopause have led to low rates of uptake. Lower-dose tamoxifen aims to reduce those side effects, but there remains some uncertainty about the minimum dose required to maintain efficacy.

The TAM-01 study, first published in 2019, demonstrated that a 5-mg dose of tamoxifen led to a reduction in recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS). At the San Antonio Breast Cancer Symposium, two studies were presented that provided insight into dose efficacy and likelihood of medication adherence in women taking baby TAM.

“We all know that women who are at increased risk for breast cancer may benefit from the use of tamoxifen to help lower their risk, although historical uptake to tamoxifen in the prevention setting has been quite low,” said Lauren Cornell, MD, during a presentation. Her team investigated the impact of patient counseling on how well they understood their risk, as well as their likelihood of adherence to the medication.

The study included 41 women, and 31 completed follow-up at 1 year. “We saw that 90% of our patients reported good or complete understanding of their breast cancer risk after the consultation, emphasizing the benefit of that consult, and 73% reported that the availability of baby tamoxifen helped in their decision to consider a preventative medication,” said Dr. Cornell during her presentation. After 1 year of follow-up, 74% said that they had initiated baby tamoxifen, and 78% of those who started taking the drug were still taking it at 1 year.

Participants who continued to take baby TAM at 1 year had a higher estimated breast cancer risk (IBIS 10-year risk, 12.7% vs 7.6%; P = .027) than those who discontinued. “We saw that uptake to baby TAM after informed discussion in patients who qualify is high, especially in those patients with high risk and intraepithelial lesions or DCIS, and adherence and tolerability at 1 year follow up is improved, compared to what we would expect with traditional dosing of tamoxifen. It’s important to note that the NCCN guidelines and the ASCO clinical practice update now include low-dose tamoxifen as an option for select women, and future randomized control trials on de-escalation of tamoxifen and high-risk patients based on their risk model assessment still need to be done. Future study should also focus on markers to identify candidates best suited for low versus standard dose of tamoxifen,” said Dr. Cornell, who is an assistant professor of medicine at Mayo Clinic Florida in Jacksonville.

At another SABCS session, Per Hall, MD, PhD, discussed findings from the previously published KARISMA-2 study, which examined efficacy of various doses of tamoxifen. A total of 1440 participants, 240 in each arm, received tamoxifen doses of 20 mg, 10 mg, 5 mg, 2.5 mg, 1 mg, or placebo. During his talk, Dr. Hall pointed out that measuring outcomes would take a very large number of participants to identify small differences in breast cancer rates. Therefore, the researchers examined breast density changes as a proxy. As a noninferiority outcome, the researchers used the proportion of women in each arm who achieved the median decrease in breast density seen at 20 mg of tamoxifen, which is 10.1%.

The women underwent mammograms at baseline and again at 6 months to determine change in breast density. Among all women in the study, the proportion of patients who had a similar breast density reduction as the 20-mg dose were very similar in the 10 mg (50.0%; P = .002), 5 mg (49.3%; P < .001), and 2.5 mg (52.5%; P < .001) groups. The 1 mg group had a proportion of 39.5% (P = .138), while the placebo group had 38.9% (P = .161). However, the results were driven by premenopausal women, where the values were 63.3%, 70.7%, 74.4%, and 69.7% in the 20-mg, 10-mg, 5-mg, and 2.5-mg groups, respectively, and 32.9% at 1 mg and 29.7% on placebo. In postmenopausal women, the values were 41.9%, 36.7%, 33.3%, and 41.9% in the 20-mg, 10-mg, 5-mg, and 2.5-mg groups, with values of 44.2% in the 1-mg group and 43.8% in the placebo group.

The median density change was 18.5% in premenopausal women and 4.0% in postmenopausal women.

“We didn’t see anything in the postmenopausal women. The decrease for those on 20 milligrams and those on placebo were exactly the same. Why this is, we still don’t know because we do know that tamoxifen in the adjuvant setting could be used for postmenopausal women. It could be that 6 months is too short of a time [to see a benefit]. We don’t know,” said Dr. Hall, who is a medical epidemiologist and biostatistician at Karolinska Institutet, Stockholm, Sweden.

Severe vasomotor side effects like hot flashes, cold flashes, and night sweats were reduced by about 50% in the lower tamoxifen doses, compared with 20 mg.

Dr. Hall also pointed out that tamoxifen is a prodrug. The CYP2D6 enzyme produces a range of metabolites, with endoxifen having the strongest affinity to the estrogen receptor and being present at the highest plasma concentration. He showed a table of endoxifen plasma levels at various tamoxifen doses in women of various metabolizer status, ranging from poor to ultrafast. Among intermediate, normal, and ultrarapid metabolizers, 5- and 10-mg doses produced plasma endoxifen levels ranging from 2.4 to 6.2 ng/mL, which represents a good therapeutic window. “For intermediate and normal metabolizers, it could be that 5 mg [of tamoxifen] is enough, but I want to underline that we didn’t use breast cancer incidence or recurrence in this study, we used density change, so we should be careful when we use these results,” said Dr. Hall. His group is now conducting the KARISMA Endoxifen trial, which will test endoxifen directly at doses of 1 and 2 mg.

Dr. Cornell has no relevant financial disclosures. Dr. Hall is a member of the scientific advisory board for Atossa Therapeutics.

SAN ANTONIO — Living in food deserts and food swamps — areas with no access to healthy food, and areas with a plethora of unhealthy food options — may raise the risk of dying from postmenopausal breast cancer, a novel ecological study has found. 

“Food deserts and food swamps are both bad, but it’s worse in food swamps,” Malcolm Bevel, PhD, MSPH, with Augusta University in Georgia, said in an interview. 

He presented his research at the San Antonio Breast Cancer Symposium. 

Breast cancer is the fourth leading cause of cancer death in the United States and is one of 13 obesity-related cancers. Healthy food consumption is a protective factor shown to decrease obesity risk and postmenopausal breast cancer mortality.

However, residing in food deserts or food swamps reduces access to healthy foods and has been severely understudied regarding postmenopausal breast cancer mortality, Dr. Bevel explained. 

To investigate, Dr. Bevel and colleagues did a cross-sectional, ecological analysis where they merged 2010 to 2020 postmenopausal breast cancer mortality data from the Centers for Disease Control and Prevention (CDC) with aggregated 2012 to 2020 data from the US Department of Agriculture Food Environment Atlas.

A food swamp score was calculated as the ratio of fast-food and convenience stores to grocery stores and farmer’s markets. 

A food desert score was calculated as the proportion of residents living more than 1 mile (urban) or 10 miles (rural) from a grocery store and household income ≤ 200% of the federal poverty threshold. 

The researchers categorized food deserts and food swamps as low, moderate, or high, with higher scores denoting counties with fewer resources for healthy food. 

Counties with high postmenopausal breast cancer mortality rates had a higher percentage of non-Hispanic Black population (5.8% vs. 2.1%), poverty rates (17.2% vs 14.2%), and adult obesity (32.5% vs 32%) and diabetes rates (11.8% vs 10.5%), compared with counties with low postmenopausal breast cancer mortality rates, Dr. Bevel reported. 

The age-adjusted odds of counties having high postmenopausal breast cancer mortality was 53% higher in counties with high food desert scores (adjusted odds ratio [aOR] 1.53; 95% CI, 1.26 - 1.88), and over twofold higher in those with high food swamp scores (aOR, 2.09; 95% CI: 1.69 - 2.58).

In fully adjusted models, the likelihood of counties having moderate postmenopausal breast cancer mortality rates was 32% higher in those with moderate food swamp scores (aOR, 1.32; 95% CI, 1.03 - 1.70).

 

Growing Epidemic Requires System Change

These findings are in line with another study by Dr. Bevel and his colleagues published earlier this year in JAMA Oncology. 

In that study, communities with easy access to fast food were 77% more likely to have high levels of obesity-related cancer mortality, as reported by this news organization. 

There is a “growing epidemic” of food deserts and food swamps in the US, which could be due to systemic issues such as gentrification/redlining and lack of investment with chain grocery stores that provide healthy food options, said Dr. Bevel. 

Local policymakers and community stakeholders could implement culturally tailored, sustainable interventions for obesity and obesity-related cancer prevention, including postmenopausal breast cancer. These could include creating more walkable neighborhoods and community vegetable gardens, he suggested. 

“This is an important study demonstrating how the environment impacts outcomes in postmenopausal women diagnosed with breast cancer,” said Lia Scott, PhD, MPH, discussant for the study.

“Most of the literature is primarily focused on food deserts to characterize the food environment. However, these authors looked at both food deserts and food swamps. And even after adjusting for various factors and age, counties with high food swamp scores at greater odds of having higher postmenopausal breast cancer mortality rates,” said Dr. Scott, who is from Georgia State University School of Public Health in Atlanta.

“There is a clear need for systems change. With ecological studies like this one, we could potentially drive policy by providing actionable data,” she added. 

The study had no specific funding. Dr. Bevel and Dr. Scott report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Living in food deserts and food swamps — areas with no access to healthy food, and areas with a plethora of unhealthy food options — may raise the risk of dying from postmenopausal breast cancer, a novel ecological study has found. 

“Food deserts and food swamps are both bad, but it’s worse in food swamps,” Malcolm Bevel, PhD, MSPH, with Augusta University in Georgia, said in an interview. 

He presented his research at the San Antonio Breast Cancer Symposium. 

Breast cancer is the fourth leading cause of cancer death in the United States and is one of 13 obesity-related cancers. Healthy food consumption is a protective factor shown to decrease obesity risk and postmenopausal breast cancer mortality.

However, residing in food deserts or food swamps reduces access to healthy foods and has been severely understudied regarding postmenopausal breast cancer mortality, Dr. Bevel explained. 

To investigate, Dr. Bevel and colleagues did a cross-sectional, ecological analysis where they merged 2010 to 2020 postmenopausal breast cancer mortality data from the Centers for Disease Control and Prevention (CDC) with aggregated 2012 to 2020 data from the US Department of Agriculture Food Environment Atlas.

A food swamp score was calculated as the ratio of fast-food and convenience stores to grocery stores and farmer’s markets. 

A food desert score was calculated as the proportion of residents living more than 1 mile (urban) or 10 miles (rural) from a grocery store and household income ≤ 200% of the federal poverty threshold. 

The researchers categorized food deserts and food swamps as low, moderate, or high, with higher scores denoting counties with fewer resources for healthy food. 

Counties with high postmenopausal breast cancer mortality rates had a higher percentage of non-Hispanic Black population (5.8% vs. 2.1%), poverty rates (17.2% vs 14.2%), and adult obesity (32.5% vs 32%) and diabetes rates (11.8% vs 10.5%), compared with counties with low postmenopausal breast cancer mortality rates, Dr. Bevel reported. 

The age-adjusted odds of counties having high postmenopausal breast cancer mortality was 53% higher in counties with high food desert scores (adjusted odds ratio [aOR] 1.53; 95% CI, 1.26 - 1.88), and over twofold higher in those with high food swamp scores (aOR, 2.09; 95% CI: 1.69 - 2.58).

In fully adjusted models, the likelihood of counties having moderate postmenopausal breast cancer mortality rates was 32% higher in those with moderate food swamp scores (aOR, 1.32; 95% CI, 1.03 - 1.70).

 

Growing Epidemic Requires System Change

These findings are in line with another study by Dr. Bevel and his colleagues published earlier this year in JAMA Oncology. 

In that study, communities with easy access to fast food were 77% more likely to have high levels of obesity-related cancer mortality, as reported by this news organization. 

There is a “growing epidemic” of food deserts and food swamps in the US, which could be due to systemic issues such as gentrification/redlining and lack of investment with chain grocery stores that provide healthy food options, said Dr. Bevel. 

Local policymakers and community stakeholders could implement culturally tailored, sustainable interventions for obesity and obesity-related cancer prevention, including postmenopausal breast cancer. These could include creating more walkable neighborhoods and community vegetable gardens, he suggested. 

“This is an important study demonstrating how the environment impacts outcomes in postmenopausal women diagnosed with breast cancer,” said Lia Scott, PhD, MPH, discussant for the study.

“Most of the literature is primarily focused on food deserts to characterize the food environment. However, these authors looked at both food deserts and food swamps. And even after adjusting for various factors and age, counties with high food swamp scores at greater odds of having higher postmenopausal breast cancer mortality rates,” said Dr. Scott, who is from Georgia State University School of Public Health in Atlanta.

“There is a clear need for systems change. With ecological studies like this one, we could potentially drive policy by providing actionable data,” she added. 

The study had no specific funding. Dr. Bevel and Dr. Scott report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

SAN ANTONIO — Living in food deserts and food swamps — areas with no access to healthy food, and areas with a plethora of unhealthy food options — may raise the risk of dying from postmenopausal breast cancer, a novel ecological study has found. 

“Food deserts and food swamps are both bad, but it’s worse in food swamps,” Malcolm Bevel, PhD, MSPH, with Augusta University in Georgia, said in an interview. 

He presented his research at the San Antonio Breast Cancer Symposium. 

Breast cancer is the fourth leading cause of cancer death in the United States and is one of 13 obesity-related cancers. Healthy food consumption is a protective factor shown to decrease obesity risk and postmenopausal breast cancer mortality.

However, residing in food deserts or food swamps reduces access to healthy foods and has been severely understudied regarding postmenopausal breast cancer mortality, Dr. Bevel explained. 

To investigate, Dr. Bevel and colleagues did a cross-sectional, ecological analysis where they merged 2010 to 2020 postmenopausal breast cancer mortality data from the Centers for Disease Control and Prevention (CDC) with aggregated 2012 to 2020 data from the US Department of Agriculture Food Environment Atlas.

A food swamp score was calculated as the ratio of fast-food and convenience stores to grocery stores and farmer’s markets. 

A food desert score was calculated as the proportion of residents living more than 1 mile (urban) or 10 miles (rural) from a grocery store and household income ≤ 200% of the federal poverty threshold. 

The researchers categorized food deserts and food swamps as low, moderate, or high, with higher scores denoting counties with fewer resources for healthy food. 

Counties with high postmenopausal breast cancer mortality rates had a higher percentage of non-Hispanic Black population (5.8% vs. 2.1%), poverty rates (17.2% vs 14.2%), and adult obesity (32.5% vs 32%) and diabetes rates (11.8% vs 10.5%), compared with counties with low postmenopausal breast cancer mortality rates, Dr. Bevel reported. 

The age-adjusted odds of counties having high postmenopausal breast cancer mortality was 53% higher in counties with high food desert scores (adjusted odds ratio [aOR] 1.53; 95% CI, 1.26 - 1.88), and over twofold higher in those with high food swamp scores (aOR, 2.09; 95% CI: 1.69 - 2.58).

In fully adjusted models, the likelihood of counties having moderate postmenopausal breast cancer mortality rates was 32% higher in those with moderate food swamp scores (aOR, 1.32; 95% CI, 1.03 - 1.70).

 

Growing Epidemic Requires System Change

These findings are in line with another study by Dr. Bevel and his colleagues published earlier this year in JAMA Oncology. 

In that study, communities with easy access to fast food were 77% more likely to have high levels of obesity-related cancer mortality, as reported by this news organization. 

There is a “growing epidemic” of food deserts and food swamps in the US, which could be due to systemic issues such as gentrification/redlining and lack of investment with chain grocery stores that provide healthy food options, said Dr. Bevel. 

Local policymakers and community stakeholders could implement culturally tailored, sustainable interventions for obesity and obesity-related cancer prevention, including postmenopausal breast cancer. These could include creating more walkable neighborhoods and community vegetable gardens, he suggested. 

“This is an important study demonstrating how the environment impacts outcomes in postmenopausal women diagnosed with breast cancer,” said Lia Scott, PhD, MPH, discussant for the study.

“Most of the literature is primarily focused on food deserts to characterize the food environment. However, these authors looked at both food deserts and food swamps. And even after adjusting for various factors and age, counties with high food swamp scores at greater odds of having higher postmenopausal breast cancer mortality rates,” said Dr. Scott, who is from Georgia State University School of Public Health in Atlanta.

“There is a clear need for systems change. With ecological studies like this one, we could potentially drive policy by providing actionable data,” she added. 

The study had no specific funding. Dr. Bevel and Dr. Scott report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.