Breast Cancer

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

TOPLINE:

Women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative invasive lobular carcinoma who are treated with endocrine therapy do not derive any additional survival benefit from neoadjuvant or adjuvant chemotherapy.

METHODOLOGY:

• Studies evaluating the long-term effects of chemotherapy in patients with invasive lobular carcinoma are limited and often “show inconclusive results,” the authors explained.
• Female patients diagnosed with ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy were identified from the breast cancer database at Erasmus Medical Center, Rotterdam, the Netherlands.
• Linked information on patient and tumor characteristics, vital status, and treatment were then obtained from the Netherlands Cancer Registry.
• Patients also had to have an indication for chemotherapy based on lymph node status, tumor size, histologic tumor grade, and hormone receptor status, in line with national guidelines.
• Among 716 patients with ER-positive, HER2-negative invasive lobular carcinoma, 520 who had an indication for chemotherapy were included. Of those, 379 received chemotherapy and 141 did not.

TAKEAWAY:

• Patients who received chemotherapy were younger at diagnosis than those who did not (51 vs 61 years), had an earlier average year of diagnosis (2010 vs 2015), and had longer follow-up (7.8 years vs 5.2 years).
• Chemotherapy recipients were more likely to have T3+ disease (33% vs 14%) and positive lymph node involvement (80% vs 49%), and less likely to undergo breast-conserving surgery (31% vs 43%).
• Researchers, however, found no difference between the chemotherapy and no-chemotherapy groups in terms of recurrence-free survival (hazard ratio [HR], 1.20; 95% CI, 0.63-2.31), breast cancer–specific survival (HR, 1.24; 95% CI, 0.60-2.58), and overall survival (HR, 0.97; 95% CI, 0.56-1.66) after adjustment for confounders.

IN PRACTICE:

The authors “observed no evidence for added value of chemotherapy” for ER-positive, HER2-negative invasive lobular carcinoma who received endocrine therapy. “In view of the adverse effects of chemotherapy, our study takes an important step in answering a valuable question from the patient’s perspective,” the researchers wrote.

SOURCE:

The study, conducted by Bernadette A.M. Heemskerk-Gerritsen, PhD, from Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, was published in Cancer on November 20, 2023.

LIMITATIONS:

The retrospective design means that there is a risk for residual confounding from factors not recorded in the database. The researchers believe that some patients did not receive chemotherapy owing to having comorbidities or patient preference, which could have influenced the results. Moreover, the duration of endocrine therapy was not recorded.

DISCLOSURES:

No funding was declared. One author declares relationships with GlaxoSmithKline, Pfizer, Menarini Silicon Biosystems, and Novartis. No other relevant financial relationships were declared.

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.

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.³ Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.⁴ A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.⁵ This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m²), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.⁶ Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.³ Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.⁴ A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.⁵ This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m²), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.⁶ Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source

Young women diagnosed with breast cancer have been shown to experience higher rates of symptoms that may adversely affect quality of life (QOL), including depression, weight gain, vasomotor symptoms, and sexual dysfunction; they may also have a harder time managing these issues.³ Chemotherapy-related amenorrhea (CRA) is one of the side effects of breast cancer treatment that can affect premenopausal women, and is associated with both patient- (age, body mass index) and treatment-related (regimen, duration) factors.⁴ A study analyzing data derived from the prospective, longitudinal Cancer Toxicities Study included 1636 premenopausal women ≤ 50 years of age with stage I-III breast cancer treated with chemotherapy but not receiving ovarian suppression (Kabirian et al). A total of 83.0% of women reported CRA at year 1, 72.5% at year 2, and 66.1% at year 4. A higher likelihood of CRA was observed for women of older age vs those age 18-34 years (adjusted odds ratio [aOR] for 35-39 years 1.84; 40-44 years 5.90; and ≥ 45 years 21.29; P < .001 for all), those who received adjuvant tamoxifen (aOR 1.97; P < .001), and those who had hot flashes at baseline (aOR 1.83; P = .01). In the QOL analysis, 57.1% reported no recovery of menses. Persistent CRA was associated with worse insomnia, more systemic therapy–related adverse effects, and worse sexual functioning. These findings highlight the importance of identifying and discussing CRA with our patients, as this can have both physical and psychological effects in the survivorship setting.

The phase 3 KEYNOTE-522 trial has established immunotherapy plus an anthracycline-based chemotherapy backbone for the treatment of stage II-III triple-negative breast cancer (TNBC), with improvements in pathologic complete response (pCR) rates and survival outcomes.⁵ This regimen can present tolerance issues in clinical practice, and rare risks for cardiotoxicity and secondary hematologic malignancies are also relevant to consider. Furthermore, some patients may not be candidates for anthracycline-based treatment due to prior receipt of a drug in this class or cardiac comorbidities. De-escalation strategies are desired to lessen toxicity and maintain (or improve) outcomes. An open-label phase 2 trial (NeoPACT) investigated the efficacy of neoadjuvant carboplatin (AUC 6), docetaxel (75 mg/m²), and pembrolizumab (200 mg) every 21 days for six cycles among 115 patients with stage I-III TNBC (Sharma et al). The overall pCR and residual cancer burden (RCB 0+1) rates were 58% (95% CI 48%-67%) and 69% (95% CI 60%-78%), respectively. Estimated 3-year event-free survival was 86% (95% CI 77%-95%) in all patients, 98% in those with a pCR, and 68% in those with residual disease. This study also demonstrated a positive association of immune biomarkers and pathologic response. The most common grade ≥ 3 treatment-related adverse events were diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%). The phase 3 SCARLET (Shorter Anthracycline-Free Chemoimmunotherapy Adapted to Pathologic Response in Early TNBC) trial is comparing the NeoPACT regimen with the standard KEYNOTE-522 regimen in early-stage TNBC and will be critical to further defining this treatment space.⁶ Presently, considering the described efficacy outcomes with the NeoPACT regimen, this regimen would be very reasonable to consider in patients who are not candidates for an anthracycline. Future prospective evaluation of immune biomarkers and additional predictors of response will also be valuable to further individualize treatment for our patients.

Additional References

1. Lambertini M, Blondeaux E, Bruzzone M, et al. Pregnancy after breast cancer: A systematic review and meta-analysis. J Clin Oncol. 2021;39:3293-3305. doi: 10.1200/JCO.21.00535
2. Partridge AH, Niman SM, Ruggeri M, et al, for the International Breast Cancer Study Group and POSITIVE Trial Collaborators. Interrupting endocrine therapy to attempt pregnancy after breast cancer. N Engl J Med. 2023;388:1645-1656. doi: 10.1056/NEJMoa2212856
3. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst. 2012;104:386-405. doi: 10.1093/jnci/djr541
4. Turnbull AK, Patel S, Martinez-Perez C, et al. Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer. Breast Cancer Res Treat. 2021;186:237-245. doi: 10.1007/s10549-020-05951-5
5. Schmid P, Cortes J, Dent R, et al; KEYNOTE-522 Investigators. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556-567. doi: 10.1056/NEJMoa2112651
6. US National Cancer Institute, Cancer Therapy Evaluation Program. Shorter anthracycline-free chemoimmunotherapy adapted to pathological response in early TNBC (SCARLET); SWOG S2212. Source

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.

Measuring serum hormone concentrations in postmenopausal women at high risk for developing breast cancer may help identify those most likely to benefit from preventive treatment with an aromatase inhibitor, according to findings from a case-control study using data from a large breast cancer prevention trial.

In the randomized, placebo-controlled IBIS-II prevention trial of 3864 women aged 40-70 years at increased risk for developing breast cancer, treatment with the aromatase inhibitor anastrozole was associated with a 49% reduction in breast cancer incidence. At median follow-up of 131 months, breast cancer occurred in 85 (4.4%) versus 165 (8.5%) of patients in the anastrozole and placebo arms, respectively.

A preplanned case-control study involving 212 participants from the anastrozole group (72 cases and 140 controls) and 416 from the placebo group (142 cases and 274 controls), showed a significant trend toward increasing breast cancer risk with increasing estradiol-to-sex hormone binding globulin (SHBG) ratio in the placebo group, but not in the anastrozole group (trend per quartile, 1.25 vs 1.06), reported Jack Cuzick, PhD, of the Wolfson Institute of Population Health, Queen Mary University of London, UK, and colleagues.

A weaker but still significant effect was observed for the testosterone-SHBG ratio in the placebo group (trend, 1.21), but again, no such effect was seen in the anastrozole group (trend, 1.18).

A relative benefit was seen for anastrozole in estradiol concentration quartiles 2, 3, and 4 (relative risk [RR], 0.55, 0.54, and 0.56, respectively), but not in quartile 1.

The findings were published online December 6 in The Lancet Oncology.

Study participants were recruited from 153 breast cancer treatment centers across 18 countries and randomized in a 1:1 ratio to receive 1 mg of oral anastrozole daily or placebo. For the case-control analysis, the investigators looked at the effects of baseline estradiol to SHBG ratio on the development of all breast cancers, including ductal carcinoma in situ. They also assessed the relative benefit of anastrozole versus placebo.

Case patients were those diagnosed with breast cancer after trial entry through data cutoff on October 22, 2019, and who had not used hormone replacement therapy within 3 months of trial entry or during the trial. Controls were participants without breast cancer who were randomly selected and matched according to treatment group, age, and follow-up time.

“Although the association between estradiol and breast cancer risk is well established, less is known about whether the concentrations of these hormones have an effect on the efficacy of preventive therapy with selective estrogen receptor modulators or aromatase inhibitors in women at increased risk of developing breast cancer,” the investigators noted, explaining that in the current analysis, they “tested the hypothesis that, for women with a low estradiol–SHBG ratio, anastrozole would provide little or no reduction in the risk of breast cancer.”

The results from the placebo group “confirm the increasing risk of breast cancer associated with higher estradiol and testosterone concentrations, and a decreasing risk associated with increasing SHBG concentrations in women who were not randomly allocated to receive anastrozole,” they said.

“However, to our knowledge, this is the first report of the effect of low concentrations of estradiol or testosterone on a lack of response to aromatase inhibitor treatment, either as a preventive measure or in the adjuvant setting,” they added. “These data provide support for the hypothesis that preventive therapy with an aromatase inhibitor is likely to be most effective for women with higher estradiol-to-SHBG ratios and, conversely, of little or no benefit for those with low estradiol-to-SHBG ratios.”

Thus, measurement of estradiol and SHBG concentrations might be helpful in making decisions about using inhibitors both for treatment and prevention, they continued, underscoring the importance of using assays sensitive enough to measure low estradiol concentrations in the plasma in postmenopausal women.

“We used a very sensitive liquid chromatography–tandem mass spectroscopy assay (lower limit of sensitivity of 3 pmol/L), which allowed us to accurately measure the low concentrations of estradiol and SHBG in the serum samples from our population of postmenopausal women. Wider use of this type of assay or a similar assay will be necessary to implement any of the actions suggested by this study,” they explained.

The findings “suggest a potential role for measuring estradiol, testosterone, and SHBG more widely, both in determining which individuals are at high risk and the likely response to endocrine treatment,” they concluded, noting that measuring serum hormones is inexpensive and, if used more routinely in high-risk clinics and for treatment of early breast cancer, could “substantially improve disease management.”

This study was funded by Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund. Dr. Cuzick reported receiving royalties from Cancer Research UK for commercial use of the IBIS (Tyrer-Cuzick) breast cancer risk evaluation software.

Measuring serum hormone concentrations in postmenopausal women at high risk for developing breast cancer may help identify those most likely to benefit from preventive treatment with an aromatase inhibitor, according to findings from a case-control study using data from a large breast cancer prevention trial.

In the randomized, placebo-controlled IBIS-II prevention trial of 3864 women aged 40-70 years at increased risk for developing breast cancer, treatment with the aromatase inhibitor anastrozole was associated with a 49% reduction in breast cancer incidence. At median follow-up of 131 months, breast cancer occurred in 85 (4.4%) versus 165 (8.5%) of patients in the anastrozole and placebo arms, respectively.

A preplanned case-control study involving 212 participants from the anastrozole group (72 cases and 140 controls) and 416 from the placebo group (142 cases and 274 controls), showed a significant trend toward increasing breast cancer risk with increasing estradiol-to-sex hormone binding globulin (SHBG) ratio in the placebo group, but not in the anastrozole group (trend per quartile, 1.25 vs 1.06), reported Jack Cuzick, PhD, of the Wolfson Institute of Population Health, Queen Mary University of London, UK, and colleagues.

A weaker but still significant effect was observed for the testosterone-SHBG ratio in the placebo group (trend, 1.21), but again, no such effect was seen in the anastrozole group (trend, 1.18).

A relative benefit was seen for anastrozole in estradiol concentration quartiles 2, 3, and 4 (relative risk [RR], 0.55, 0.54, and 0.56, respectively), but not in quartile 1.

The findings were published online December 6 in The Lancet Oncology.

Study participants were recruited from 153 breast cancer treatment centers across 18 countries and randomized in a 1:1 ratio to receive 1 mg of oral anastrozole daily or placebo. For the case-control analysis, the investigators looked at the effects of baseline estradiol to SHBG ratio on the development of all breast cancers, including ductal carcinoma in situ. They also assessed the relative benefit of anastrozole versus placebo.

Case patients were those diagnosed with breast cancer after trial entry through data cutoff on October 22, 2019, and who had not used hormone replacement therapy within 3 months of trial entry or during the trial. Controls were participants without breast cancer who were randomly selected and matched according to treatment group, age, and follow-up time.

“Although the association between estradiol and breast cancer risk is well established, less is known about whether the concentrations of these hormones have an effect on the efficacy of preventive therapy with selective estrogen receptor modulators or aromatase inhibitors in women at increased risk of developing breast cancer,” the investigators noted, explaining that in the current analysis, they “tested the hypothesis that, for women with a low estradiol–SHBG ratio, anastrozole would provide little or no reduction in the risk of breast cancer.”

The results from the placebo group “confirm the increasing risk of breast cancer associated with higher estradiol and testosterone concentrations, and a decreasing risk associated with increasing SHBG concentrations in women who were not randomly allocated to receive anastrozole,” they said.

“However, to our knowledge, this is the first report of the effect of low concentrations of estradiol or testosterone on a lack of response to aromatase inhibitor treatment, either as a preventive measure or in the adjuvant setting,” they added. “These data provide support for the hypothesis that preventive therapy with an aromatase inhibitor is likely to be most effective for women with higher estradiol-to-SHBG ratios and, conversely, of little or no benefit for those with low estradiol-to-SHBG ratios.”

Thus, measurement of estradiol and SHBG concentrations might be helpful in making decisions about using inhibitors both for treatment and prevention, they continued, underscoring the importance of using assays sensitive enough to measure low estradiol concentrations in the plasma in postmenopausal women.

“We used a very sensitive liquid chromatography–tandem mass spectroscopy assay (lower limit of sensitivity of 3 pmol/L), which allowed us to accurately measure the low concentrations of estradiol and SHBG in the serum samples from our population of postmenopausal women. Wider use of this type of assay or a similar assay will be necessary to implement any of the actions suggested by this study,” they explained.

The findings “suggest a potential role for measuring estradiol, testosterone, and SHBG more widely, both in determining which individuals are at high risk and the likely response to endocrine treatment,” they concluded, noting that measuring serum hormones is inexpensive and, if used more routinely in high-risk clinics and for treatment of early breast cancer, could “substantially improve disease management.”

This study was funded by Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund. Dr. Cuzick reported receiving royalties from Cancer Research UK for commercial use of the IBIS (Tyrer-Cuzick) breast cancer risk evaluation software.

Measuring serum hormone concentrations in postmenopausal women at high risk for developing breast cancer may help identify those most likely to benefit from preventive treatment with an aromatase inhibitor, according to findings from a case-control study using data from a large breast cancer prevention trial.

In the randomized, placebo-controlled IBIS-II prevention trial of 3864 women aged 40-70 years at increased risk for developing breast cancer, treatment with the aromatase inhibitor anastrozole was associated with a 49% reduction in breast cancer incidence. At median follow-up of 131 months, breast cancer occurred in 85 (4.4%) versus 165 (8.5%) of patients in the anastrozole and placebo arms, respectively.

A preplanned case-control study involving 212 participants from the anastrozole group (72 cases and 140 controls) and 416 from the placebo group (142 cases and 274 controls), showed a significant trend toward increasing breast cancer risk with increasing estradiol-to-sex hormone binding globulin (SHBG) ratio in the placebo group, but not in the anastrozole group (trend per quartile, 1.25 vs 1.06), reported Jack Cuzick, PhD, of the Wolfson Institute of Population Health, Queen Mary University of London, UK, and colleagues.

A weaker but still significant effect was observed for the testosterone-SHBG ratio in the placebo group (trend, 1.21), but again, no such effect was seen in the anastrozole group (trend, 1.18).

A relative benefit was seen for anastrozole in estradiol concentration quartiles 2, 3, and 4 (relative risk [RR], 0.55, 0.54, and 0.56, respectively), but not in quartile 1.

The findings were published online December 6 in The Lancet Oncology.

Study participants were recruited from 153 breast cancer treatment centers across 18 countries and randomized in a 1:1 ratio to receive 1 mg of oral anastrozole daily or placebo. For the case-control analysis, the investigators looked at the effects of baseline estradiol to SHBG ratio on the development of all breast cancers, including ductal carcinoma in situ. They also assessed the relative benefit of anastrozole versus placebo.

Case patients were those diagnosed with breast cancer after trial entry through data cutoff on October 22, 2019, and who had not used hormone replacement therapy within 3 months of trial entry or during the trial. Controls were participants without breast cancer who were randomly selected and matched according to treatment group, age, and follow-up time.

“Although the association between estradiol and breast cancer risk is well established, less is known about whether the concentrations of these hormones have an effect on the efficacy of preventive therapy with selective estrogen receptor modulators or aromatase inhibitors in women at increased risk of developing breast cancer,” the investigators noted, explaining that in the current analysis, they “tested the hypothesis that, for women with a low estradiol–SHBG ratio, anastrozole would provide little or no reduction in the risk of breast cancer.”

The results from the placebo group “confirm the increasing risk of breast cancer associated with higher estradiol and testosterone concentrations, and a decreasing risk associated with increasing SHBG concentrations in women who were not randomly allocated to receive anastrozole,” they said.

“However, to our knowledge, this is the first report of the effect of low concentrations of estradiol or testosterone on a lack of response to aromatase inhibitor treatment, either as a preventive measure or in the adjuvant setting,” they added. “These data provide support for the hypothesis that preventive therapy with an aromatase inhibitor is likely to be most effective for women with higher estradiol-to-SHBG ratios and, conversely, of little or no benefit for those with low estradiol-to-SHBG ratios.”

Thus, measurement of estradiol and SHBG concentrations might be helpful in making decisions about using inhibitors both for treatment and prevention, they continued, underscoring the importance of using assays sensitive enough to measure low estradiol concentrations in the plasma in postmenopausal women.

“We used a very sensitive liquid chromatography–tandem mass spectroscopy assay (lower limit of sensitivity of 3 pmol/L), which allowed us to accurately measure the low concentrations of estradiol and SHBG in the serum samples from our population of postmenopausal women. Wider use of this type of assay or a similar assay will be necessary to implement any of the actions suggested by this study,” they explained.

The findings “suggest a potential role for measuring estradiol, testosterone, and SHBG more widely, both in determining which individuals are at high risk and the likely response to endocrine treatment,” they concluded, noting that measuring serum hormones is inexpensive and, if used more routinely in high-risk clinics and for treatment of early breast cancer, could “substantially improve disease management.”

This study was funded by Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund. Dr. Cuzick reported receiving royalties from Cancer Research UK for commercial use of the IBIS (Tyrer-Cuzick) breast cancer risk evaluation software.

Key clinical point: Chemotherapy failed to show long-term survival benefits in patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2−) invasive lobular breast cancer (BC) treated with adjuvant endocrine therapy.

Major finding: Patients who did vs did not receive chemotherapy had comparable recurrence-free survival (hazard ratio [HR] 1.20; 95% CI 0.63-2.31), breast cancer-specific survival (HR 1.24; 95% CI 0.60-2.58), and overall survival (HR 0.97; 95% CI 0.56-1.66) outcomes.

Study details: Findings are from a retrospective cohort study including 520 women with ER+/HER2− invasive lobular BC treated with adjuvant endocrine therapy who had an indication for chemotherapy, 379 of whom received chemotherapy.

Disclosures: This study did not receive any funding. JWM Martens declared receiving grants from and serving as a consultant for various sources. The other authors declared no conflicts of interest.

Source: Öztekin S et al. The effect of (neo)adjuvant chemotherapy on long-term survival outcomes in patients with invasive lobular breast cancer treated with endocrine therapy: A retrospective cohort study. Cancer. 2023 (Nov 20). doi: 10.1002/cncr.35125

Key clinical point: Chemotherapy failed to show long-term survival benefits in patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2−) invasive lobular breast cancer (BC) treated with adjuvant endocrine therapy.

Major finding: Patients who did vs did not receive chemotherapy had comparable recurrence-free survival (hazard ratio [HR] 1.20; 95% CI 0.63-2.31), breast cancer-specific survival (HR 1.24; 95% CI 0.60-2.58), and overall survival (HR 0.97; 95% CI 0.56-1.66) outcomes.

Study details: Findings are from a retrospective cohort study including 520 women with ER+/HER2− invasive lobular BC treated with adjuvant endocrine therapy who had an indication for chemotherapy, 379 of whom received chemotherapy.

Disclosures: This study did not receive any funding. JWM Martens declared receiving grants from and serving as a consultant for various sources. The other authors declared no conflicts of interest.

Source: Öztekin S et al. The effect of (neo)adjuvant chemotherapy on long-term survival outcomes in patients with invasive lobular breast cancer treated with endocrine therapy: A retrospective cohort study. Cancer. 2023 (Nov 20). doi: 10.1002/cncr.35125

Key clinical point: Chemotherapy failed to show long-term survival benefits in patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2−) invasive lobular breast cancer (BC) treated with adjuvant endocrine therapy.

Major finding: Patients who did vs did not receive chemotherapy had comparable recurrence-free survival (hazard ratio [HR] 1.20; 95% CI 0.63-2.31), breast cancer-specific survival (HR 1.24; 95% CI 0.60-2.58), and overall survival (HR 0.97; 95% CI 0.56-1.66) outcomes.

Study details: Findings are from a retrospective cohort study including 520 women with ER+/HER2− invasive lobular BC treated with adjuvant endocrine therapy who had an indication for chemotherapy, 379 of whom received chemotherapy.

Disclosures: This study did not receive any funding. JWM Martens declared receiving grants from and serving as a consultant for various sources. The other authors declared no conflicts of interest.

Source: Öztekin S et al. The effect of (neo)adjuvant chemotherapy on long-term survival outcomes in patients with invasive lobular breast cancer treated with endocrine therapy: A retrospective cohort study. Cancer. 2023 (Nov 20). doi: 10.1002/cncr.35125

Key clinical point: The combination of neoadjuvant immunotherapy (nIO) and chemotherapy led to significant improvements in survival outcomes and should be administered as the standard treatment in patients with stages II-III triple-negative breast cancer (TNBC).

Major finding: Patients who did vs did not receive nIO had ~40% lower odds of disease recurrence or death (event-free survival: hazard ratio [HR] 0.61; P < .001) or only death (overall survival: HR 0.62; P < 0.001).

Study details: Findings are from a meta-analysis of four randomized controlled trials including patients with stages II-III TNBC who were randomly assigned to receive either chemotherapy plus nIO or treatment without nIO.

Disclosures: This study did not disclose any funding source. Some authors declared serving in consulting or advisory roles, receiving educational or financial support, research or travel grant, research funding, speaker fees, or honoraria from, or having other ties with various sources.

Source: Cunha MT et al. Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: An extracted individual patient data and trial-level meta-analysis. Br J Cancer. 2023 (Nov 27). doi: 10.1038/s41416-023-02501-w

Key clinical point: The combination of neoadjuvant immunotherapy (nIO) and chemotherapy led to significant improvements in survival outcomes and should be administered as the standard treatment in patients with stages II-III triple-negative breast cancer (TNBC).

Major finding: Patients who did vs did not receive nIO had ~40% lower odds of disease recurrence or death (event-free survival: hazard ratio [HR] 0.61; P < .001) or only death (overall survival: HR 0.62; P < 0.001).

Study details: Findings are from a meta-analysis of four randomized controlled trials including patients with stages II-III TNBC who were randomly assigned to receive either chemotherapy plus nIO or treatment without nIO.

Disclosures: This study did not disclose any funding source. Some authors declared serving in consulting or advisory roles, receiving educational or financial support, research or travel grant, research funding, speaker fees, or honoraria from, or having other ties with various sources.

Source: Cunha MT et al. Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: An extracted individual patient data and trial-level meta-analysis. Br J Cancer. 2023 (Nov 27). doi: 10.1038/s41416-023-02501-w

Key clinical point: The combination of neoadjuvant immunotherapy (nIO) and chemotherapy led to significant improvements in survival outcomes and should be administered as the standard treatment in patients with stages II-III triple-negative breast cancer (TNBC).

Major finding: Patients who did vs did not receive nIO had ~40% lower odds of disease recurrence or death (event-free survival: hazard ratio [HR] 0.61; P < .001) or only death (overall survival: HR 0.62; P < 0.001).

Study details: Findings are from a meta-analysis of four randomized controlled trials including patients with stages II-III TNBC who were randomly assigned to receive either chemotherapy plus nIO or treatment without nIO.

Disclosures: This study did not disclose any funding source. Some authors declared serving in consulting or advisory roles, receiving educational or financial support, research or travel grant, research funding, speaker fees, or honoraria from, or having other ties with various sources.

Source: Cunha MT et al. Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: An extracted individual patient data and trial-level meta-analysis. Br J Cancer. 2023 (Nov 27). doi: 10.1038/s41416-023-02501-w

Key clinical point: Taxane + anthracycline-based chemotherapy (ATAX) vs taxane-based chemotherapy (TAX) did not increase the risk for major cardiovascular adverse events in older patients with early-stage triple-negative breast cancer (TNBC) or affect survival outcomes in those who had a cardiac event.

Major finding: The risks for acute myocardial infarction, potentially fatal arrhythmia, and cerebral vascular accident did not increase (all P > .1) and the risk for subsequent heart failure was lower in patients receiving ATAX vs TAX (odds ratio 0.63; P < .01). In patients who experienced a cardiac event, ATAX vs TAX did not worsen the survival outcomes.

Study details: This study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and included 2215 older women (age ≥ 66 years) diagnosed with early-stage TNBC who received ATAX (39.78%) or TAX (60.26%) in an adjuvant setting.

Disclosures: This study was funded by the Women’s Cancer Developmental Therapeutics Program, University of Colorado Cancer Center. The authors declared no conflicts of interest.

Source: Roy S et al. Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane  + anthracycline versus taxane-based chemotherapy regimens: A SEER-Medicare study. Eur J Cancer. 2023;196:113426 (Nov 11). doi: 10.1016/j.ejca.2023.113426

Key clinical point: Taxane + anthracycline-based chemotherapy (ATAX) vs taxane-based chemotherapy (TAX) did not increase the risk for major cardiovascular adverse events in older patients with early-stage triple-negative breast cancer (TNBC) or affect survival outcomes in those who had a cardiac event.

Major finding: The risks for acute myocardial infarction, potentially fatal arrhythmia, and cerebral vascular accident did not increase (all P > .1) and the risk for subsequent heart failure was lower in patients receiving ATAX vs TAX (odds ratio 0.63; P < .01). In patients who experienced a cardiac event, ATAX vs TAX did not worsen the survival outcomes.

Study details: This study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and included 2215 older women (age ≥ 66 years) diagnosed with early-stage TNBC who received ATAX (39.78%) or TAX (60.26%) in an adjuvant setting.

Disclosures: This study was funded by the Women’s Cancer Developmental Therapeutics Program, University of Colorado Cancer Center. The authors declared no conflicts of interest.

Source: Roy S et al. Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane  + anthracycline versus taxane-based chemotherapy regimens: A SEER-Medicare study. Eur J Cancer. 2023;196:113426 (Nov 11). doi: 10.1016/j.ejca.2023.113426

Key clinical point: Taxane + anthracycline-based chemotherapy (ATAX) vs taxane-based chemotherapy (TAX) did not increase the risk for major cardiovascular adverse events in older patients with early-stage triple-negative breast cancer (TNBC) or affect survival outcomes in those who had a cardiac event.

Major finding: The risks for acute myocardial infarction, potentially fatal arrhythmia, and cerebral vascular accident did not increase (all P > .1) and the risk for subsequent heart failure was lower in patients receiving ATAX vs TAX (odds ratio 0.63; P < .01). In patients who experienced a cardiac event, ATAX vs TAX did not worsen the survival outcomes.

Study details: This study analyzed the data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and included 2215 older women (age ≥ 66 years) diagnosed with early-stage TNBC who received ATAX (39.78%) or TAX (60.26%) in an adjuvant setting.

Disclosures: This study was funded by the Women’s Cancer Developmental Therapeutics Program, University of Colorado Cancer Center. The authors declared no conflicts of interest.

Source: Roy S et al. Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane  + anthracycline versus taxane-based chemotherapy regimens: A SEER-Medicare study. Eur J Cancer. 2023;196:113426 (Nov 11). doi: 10.1016/j.ejca.2023.113426

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Tumor involvement within the axillary soft tissue extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) should be pathologically evaluated in patients with LN+ breast cancer (BC) as it is a significant predictor of worsened prognostic outcomes for this population.

Major finding: Axillary soft tissue involvement is significantly associated with worsened distant failure (hazard ratio [HR] 1.6; P < .001), locoregional failure (HR 2.3; P < .001), and axillary failure (HR 3.3; P = .003). The delivery of regional lymph node radiation improved the locoregional tumor outcomes in patients with axillary soft tissue involvement, ECE, or both (HR 0.5; P = .03).

Study details: Findings are from a retrospective review including 2162 patients with LN+ invasive BC tumors.

Disclosures: One author declared receiving financial support for this study. Two authors declared being employees of, receiving research funding, or honoraria from, or having other ties with various sources.

Source: Naoum GE, Oladero O, et al. Pathological exploration of the axillary soft tissue microenvironment and its impact on axillary management and breast cancer outcomes. J Clin Oncol. 2023 (Nov 15). doi: 10.1200/JCO.23.01009

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910

Key clinical point: Chemotherapy-related amenorrhea (CRA) was common in premenopausal women with stages I-III breast cancer (BC), particularly in those who were older, experienced hot flashes, or received adjuvant tamoxifen.

Major finding: The majority (57.1%) of premenopausal patients with BC reported having persistent CRA, with the likelihood increasing in those who were age ≥ 35 years (adjusted odds ratio [aOR] 35-39 years: 1.84, 40-44 years: 5.90, ≥45 years: 21.29; all P < .001), experienced hot flashes at diagnosis (aOR 1.83; P = .01), or received adjuvant tamoxifen (aOR 1.97; P < .001).

Study details: This study analyzed the data from the Cancer Toxicities Study and included 1636 premenopausal women with stages I-III BC who were age < 50 years and received chemotherapy but not ovarian function suppressants.

Disclosures: MA Franzoi, M Lambertini, and A Di Meglio received grants or awards for this study. Some authors declared receiving personal fees, speaking fees, grants, or honoraria from or having other ties with various sources.

Source: Kabirian R et al. Chemotherapy-related amenorrhea and quality of life among premenopausal women with breast cancer. JAMA Netw Open. 2023;6(11):e2343910 (Nov 16). doi: 10.1001/jamanetworkopen.2023.43910