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Anthracycline-free neoadjuvant carboplatin and docetaxel + pembrolizumab show encouraging outcomes in TNBC
Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).
Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.
Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.
Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.
Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033
Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).
Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.
Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.
Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.
Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033
Key clinical point: Neoadjuvant carboplatin and docetaxel + pembrolizumab showed encouraging pathological complete response (pCR) rates and 3-year event-free survival (EFS) outcomes and had a manageable safety profile in patients with stages I-III triple-negative breast cancer (TNBC).
Major finding: The overall pCR rate was 58% (95% CI 48%-67%), with the estimated 3-year EFS rates being 86% (95% CI 77%-95%) in all patients and 98% (95% CI 95%-100%) in patients who achieved pCR. Diarrhea (4.3%), anemia (3.5%), and peripheral sensory neuropathy (2.6%) were the most common grade ≥ 3 treatment-related adverse events, and one study-related death was reported.
Study details: Findings are from the phase 2 NeoPACT trial including 115 female patients with stages I-III TNBC who received carboplatin and docetaxel + pembrolizumab in a neoadjuvant setting.
Disclosures: This study was supported by the University of Kansas Cancer Center and others. The lead author and other authors declared receiving research funding, royalties, personal, consulting or speaking fees from, being advisory board members of, or having other ties with various sources.
Source: Sharma P et al. Clinical and biomarker findings of neoadjuvant pembrolizumab and carboplatin plus docetaxel in triple-negative breast cancer: NeoPACT phase 2 clinical trial. JAMA Oncol. 2023 (Nov 22). doi: 10.1001/jamaoncol.2023.5033
Preoperative MRI may allow radiotherapy omission in some women with early BC
Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.
Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.
Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.
Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.
Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5
Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.
Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.
Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.
Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.
Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5
Key clinical point: Women with apparently unifocal, non–triple-negative breast cancer (BC) who underwent preoperative magnetic resonance imaging (MRI) and did not have any occult malignancy may safely forgo radiation therapy.
Major finding: Preoperative MRI detected malignant occult lesions in 11% of patients with BC. At 5 years, the ipsilateral invasive recurrence rate was very low (1.0%; upper 95% CI 5.4%) in patients with no occult malignancy who did not receive adjuvant radiotherapy.
Study details: Findings are from the prospective 2-arm PROSPECT study that included 443 patients with non–triple-negative, clinical stage T1N0, apparently unifocal BC who underwent MRI, of whom 201 patients underwent breast-conserving surgery without radiotherapy and 242 women were deemed ineligible for radiotherapy omission.
Disclosures: This study was funded by the Breast Cancer Trials, Australia, and other sources. The authors declared no conflicts of interest.
Source: Mann GB et al. Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): Primary results of a prospective two-arm study. Lancet. 2023 (Dec 5). doi: 10.1016/S0140-6736(23)02476-5
Cholesterol-lowering interventions with statins may improve prognosis in BC
Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.
Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).
Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.
Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.
Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861
Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.
Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).
Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.
Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.
Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861
Key clinical point: The post-diagnostic use of statins lowered the risk for mortality in patients with newly diagnosed breast cancer (BC) only in case of a subsequent lowering of serum cholesterol levels.
Major finding: Compared with patients who did not receive statins, the risk for BC-specific mortality was significantly reduced in those who received statins after BC diagnosis and reported a subsequent reduction in the median total cholesterol level (adjusted hazard ratio 0.49; P = .001). No mortality-risk reduction was observed in patients whose cholesterol levels did not decrease after the post-diagnostic initiation of statins (P = .30).
Study details: This retrospective population-based cohort study included 13,378 patients with newly diagnosed invasive BC, of whom 980 patients initiated statins after BC diagnosis.
Disclosures: This study was supported by research funds and a grant from the Pirkanmaa Hospital District and Duodecim, Finland, respectively. Two authors declared receiving grants or personal fees from various sources, including the Pirkanmaa Hospital District. The other authors declared no conflicts of interest.
Source: Murto MO et al. Statin use, cholesterol level, and mortality among females with breast cancer. JAMA Netw Open. 2023;6(11):e2343861 (Nov 17). doi: 10.1001/jamanetworkopen.2023.43861
Pemetrexed + vinorelbine bests vinolrelbine monotherapy in metastatic BC in phase 2
Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.
Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.
Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.
Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.
Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456
Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.
Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.
Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.
Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.
Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456
Key clinical point: Pemetrexed + vinorelbine vs vinorelbine monotherapy led to a greater improvement in progression-free survival (PFS) outcomes and had a manageable safety profile in patients with metastatic breast cancer (BC) previously treated with anthracycline and taxane.
Major finding: The median PFS improved by 45% with pemetrexed + vinorelbine vs vinorelbine monotherapy (5.7 vs 1.6 months; hazard ratio 0.55; P = .001). Pemetrexed + vinorelbine also had a manageable safety profile in general.
Study details: Findings are from the phase 2 KCSG-BR15-17 trial including 125 patients with metastatic BC who had been treated with anthracycline and taxane previously and were randomly assigned to receive pemetrexed + vinorelbine or vinorelbine monotherapy.
Disclosures: This study was funded by a grant from the Ministry of Health and Welfare, Republic of Korea. Two authors declared receiving research funding or research drug supply from or serving in consulting or advisory roles for various sources. The other authors declared no conflicts of interest.
Source: Lee DW, Jung KH, et al. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open label, multicenter, phase II trial. Eur J Cancer. 2023;113456 (Nov 20). doi: 10.1016/j.ejca.2023.113456
Young BRCA carriers with BC history may safely opt for pregnancy
Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.
Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).
Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.
Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.
Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463
Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.
Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).
Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.
Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.
Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463
Key clinical point: Women with germline BRCA1 or BRCA2 pathogenic mutations who had a pregnancy after diagnosis of early breast cancer (BC) reported prognostic outcomes similar to that of women without a pregnancy.
Major finding: The cumulative incidence of pregnancy was 22% at 10 years. The disease-free survival outcomes were comparable between patients with BC who did vs did not become pregnant (adjusted hazard ratio 0.99; P = .90).
Study details: Findings are from a retrospective cohort study including 4732 young women age ≤ 40 years with a history of BC who had germline pathogenic BRCA mutations, of whom 659 women reported ≥1 pregnancy after BC.
Disclosures: The study was partly supported by the Italian Association for Cancer Research and the 2022 Gilead Research Scholars Program in Solid Tumors. The authors declared receiving speaker honoraria, travel grants, research funding, or speaker fees from and having other ties with Gilead and several other sources.
Source: Lambertini M et al. Pregnancy after breast cancer in young BRCA carriers: An international hospital-based cohort study. JAMA. 2023 (Dec 7). doi: 10.1001/jama.2023.25463
Updates on Investigational Treatments for HR-Positive, HER2-Negative Breast Cancer
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Results from TROPION-Breast01, EMBER, and OPERA were recently presented at ESMO Breast Cancer 2023.
A number of exciting updates on systemic therapies for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancer were presented at the European Society for Medical Oncology (ESMO) Breast Cancer 2023, including novel endocrine agents and antibody-drug conjugates (ADC). We have highlighted 3 key studies, including the phase III study of datopotamab deruxtecan (Dato-DXd), the new trophoblast cell surface antigen 2 (TROP2)-directed ADC; the phase I study of imlunestrant, a selective estrogen receptor degrader (SERD); and phase I/II data evaluating OP-1250, a small molecule oral complete estrogen receptor antagonist (CERAN) and SERD.
TROPION-Breast01: Dato-DXd Improves Progression-Free Survival Compared With Systemic Chemotherapy
Study synopsis
Dato-DXd, an investigational TROP2 ADC, resulted in significantly improved progression-free survival (PFS) when compared with investigator’s choice chemotherapy (ICC) in individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer, according to a randomized phase III trial.
Participants in the study had progressed on or were not eligible for endocrine therapy and had received 1 or 2 prior lines of systemic chemotherapy. Patients were randomized to receive either 6 mg/kg of Dato-DXd once every 3 weeks (n=365; median age 56), or ICC with eribulin, vinorelbine, capecitabine, or gemcitabine (n=367; median age 54) until progression or unacceptable toxicity. Blinded independent review assessed PFS and overall survival. Among the results:
In the blinded independent review, PFS was 6.9 months for Dato-DXd and 4.9 months for ICC (HR 0.63 [95% CI: 0.52, 0.76]; p<0.0001)
At 6 months, 53% of participants receiving Dato-DXd achieved PFS, compared with 39% in the systemic chemotherapy contingent
In the Dato-DXd group, treatment-related adverse events led to dose reductions in 23% and discontinuation in 3% of patients
In the systemic chemotherapy cohort, the dose reduction and discontinuation rates were 32% and 3%, respectively
At the time data were reported at ESMO, overall survival data were not mature but trending favorably for Dato-DXd
The investigators concluded that Dato-DXd is a promising novel treatment option for individuals with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer who have received prior chemotherapy.
EMBER: Imlunestrant Alone or With a Kinase Inhibitor: Early Safety and Efficacy Results Are Encouraging
Study synopsis
The SERD imlunestrant—used either alone or combined with a kinase inhibitor—showed favorable efficacy in individuals with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, according to the first set of clinical data reported from the phase 1a/b EMBER study.
Key eligibility criteria for phase 1b enrollment included prior sensitivity to endocrine therapy, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Prior therapies included endocrine therapy (100%), CDK4/6 inhibitors (100%), hormonal therapy with fulvestrant (35%), and chemotherapy (17%). At baseline, 46% of patients had visceral disease and 46% had an ESR1 mutation. Participants received imlunestrant alone (n=114) or with the kinase inhibitors everolimus (n=42) or alpelisib (n=21). Investigators assessed each regimen’s safety profile, as well as the objective response rate and clinical benefit rate.
The safety profile of each regimen was similar to those seen with everolimus and alpelisib alone. No cardiac or ocular toxicities were observed. Regarding grade ≥3 treatment-related adverse events:
The imlunestrant alone group experienced fatigue (2%) and neutropenia (2%)
The imlunestrant + everolimus group experienced hypertriglyceridemia (5%) and aspartate aminotransferase increase (5%)
The imlunestrant + alpelisib cohort experienced rash (43%) and hyperglycemia (10%).
In the imlunestrant alone group, 2% of individuals had their doses reduced due to adverse events; none discontinued treatment
In the imlunestrant + everolimus cohort, 12% of patients experienced dose reduction due to everolimus and 2% due to both medications; 2% discontinued treatment due to everolimus
In the imlunestrant + alpelisib cohort, 24% of patients experienced dose reduction due to alpelisib and 14% due to both medications; 29% discontinued treatment due to alpelisib
Regarding efficacy:
The objective response rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 9%, 21%, and 50%, respectively
The clinical benefit rates in the imlunestrant alone, imlunestrant + everolimus, and imlunestrant + alpelisib groups were 42%, 62%, and 62%, respectively
Investigators concluded that imlunestrant used alone or in combination with 1 of the 2 kinase inhibitors demonstrated robust efficacy in individuals with pretreated, ER-positive, HER2-negative advanced breast cancer.
OPERA: OP-1250 Paired With a CDK4/6 Inhibitor: Anti-Tumor Activity With No Dose-Limiting Toxicities
Study synopsis
OP-1250, a CERAN and SERD, continues to show promising results when paired with a CDK4/6 inhibitor. The combination of OP-1250 and the CDK4/6 inhibitor palbociclib appears to be well tolerated and has a similar safety profile to each drug when used alone, according to a phase I/II study involving 20 individuals with pretreated ER-positive, HER2-negative breast cancer.
Participants had advanced or metastatic ER-positive, HER2-negative breast cancer that progressed on ≤1 lines of endocrine therapy. Fourteen participants had received prior CDK4/6 inhibitor therapy, including 11 who were previously treated with palbociclib. Patients received escalating doses of OP-1250 with 125 mg of palbociclib orally daily for 21 of 28 days. OP-1250 doses were 30 mg (n=3), 60 mg (n=3), 90 mg (n=3), and 120 mg (n=11). Investigators assessed pharmacokinetics, drug-drug interactions, safety, and efficacy. Among the results observed to date:
Grade 3 neutropenia occurred in 55% of participants
There were no grade 4 treatment-related adverse events and no dose-limiting toxicities
OP-1250 exposure yielded similar results to what was seen in the previous monotherapy study
Palbociclib exposure was comparable to published monotherapy data when combined with OP-1250 for all dosages
Investigators observed antitumor activity, including partial responses
Researchers concluded that OP-1250 does not affect the pharmacokinetics of palbociclib, and there do not appear to be drug-drug interactions. Tumor response to this combination was encouraging and requires continued investigation.
Conclusions
These 3 studies presented at ESMO 2023 highlight exciting novel therapies for the treatment of HR-positive, HER2-low, and HER2-negative metastatic breast cancer. The EMBER and OPERA updates provide support for the safety and efficacy of these novel endocrine agents in combination with kinase inhibitors and CDK4/6 inhibitors, respectively, in patients with endocrine-sensitive disease, while the TROPION-01 study demonstrates the encouraging efficacy and safety of a second TROP-2-directed ADC in a more heavily pretreated population.
Survival-Toxicity Trade-off With T-DM1 in HER+ Breast Cancer
SAN ANTONIO — 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 — 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 — 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.
AT SABCS 2023
Pregnancy safe after BRCA-mutated breast cancer
SAN ANTONIO — New research provides some reassuring news for young women hoping to become pregnant after a diagnosis of BRCA-mutated breast cancer.
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.
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.
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.
FROM SABCS 2023
Patients with HR-positive breast cancer can safely use ART
SAN ANTONIO — 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 — 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 — 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.
FROM SABCS 2023
Less is more for axillary surgery in early breast cancer
SAN ANTONIO — 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 — 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 — 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.
FROM SABCS 2023