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Extended Endocrine Therapy and Survival for Breast Cancer Subtypes in Premenopausal Patients
Carmine Valenza1,2,3,4,5, Yue Zheng6, Monica Milano7
1Harvard Chan School of Public Health, Harvard University, Boston, Massachusetts.
JAMA Network Open
|May 4, 2026
Summary
Extended endocrine therapy (EET) may reduce recurrence risk in premenopausal women with early breast cancer. The greatest benefit was observed in those with luminal A-like disease, suggesting personalized treatment approaches for hormone receptor-positive breast cancer.
Area of Science:
- Oncology
- Endocrinology
- Clinical Research
Background:
- Premenopausal women with node-positive, hormone receptor-positive early breast cancer benefit from extended endocrine therapy (EET) after initial treatment.
- The impact of EET on recurrence risk may vary across different breast cancer subtypes.
Purpose of the Study:
- To evaluate the risk of invasive and distant recurrence in premenopausal patients with node-positive, hormone receptor-positive early breast cancer.
- To assess recurrence risk across surrogate breast cancer subtypes in patients who received EET versus those who did not, after completing 5 years of adjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy.
Main Methods:
- A multicenter cohort study utilizing data from the Young Women's Breast Cancer Study and the European Institute of Oncology Breast Cancer cohort.
- Included were 487 premenopausal patients diagnosed with early breast cancer (node-positive, hormone receptor-positive) who remained premenopausal after 5 years of adjuvant LHRH agonist therapy without recurrence.
- Propensity score (PS) weighting analysis was used to compare invasive breast cancer-free survival and distant recurrence-free survival (DRFS) between patients who received EET and those who did not.
Main Results:
- Overall, 276 patients received EET for a median of 3.7 years. The cohort comprised luminal A-like (18%), luminal B-like (61%), and ERBB2-positive (21%) disease subtypes.
- PS-weighted analysis showed a reduced risk of invasive breast cancer recurrence with EET across all subtypes (HR range: 0.62-0.68).
- The cause-specific PS-weighted hazard ratio for DRFS was significantly lower with EET in luminal A-like (HR: 0.25) and luminal B-like/ERBB2-negative (HR: 0.54) disease, but not significantly in ERBB2-positive disease (HR: 0.54).
Conclusions:
- Extended endocrine therapy (EET) demonstrated a lower estimated risk of recurrence across all surrogate breast cancer subtypes in premenopausal women.
- The most significant benefit of EET was observed in patients with luminal A-like disease.
- Further validation in larger, prospective studies is warranted to confirm these findings and inform personalized treatment strategies.
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