Questioning the benefit of adjuvant chemotherapy in premenopausal HR+/HER2– early breast cancer: Real-world evidence from an Asian cohort.

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Background: The benefit of adjuvant chemotherapy in premenopausal women with hormone receptor (HR)–positive, HER2-negative early breast cancer remains controversial. Randomized trials such as TAILORx and RxPONDER suggest improved outcomes in younger patients, yet it remains unclear whether this benefit reflects direct cytotoxic effects or chemotherapy-induced ovarian function suppression. Real-world data addressing this question in Asian populations are limited. Methods: We conducted a retrospective cohort study of 3,152 women diagnosed with HR-positive, HER2-negative early breast cancer between 2004 and 2019 at a tertiary medical center. Patients receiving endocrine therapy alone were compared with those receiving chemoendocrine therapy. Primary endpoints included invasive disease-free survival (IDFS), distant metastasis-free survival (DMFS), and overall survival (OS). Multivariable Cox proportional hazards models and restricted cubic splines were used to evaluate age-dependent treatment effects. Results: Among the study cohort, 1,473 patients (47%) received endocrine therapy alone, whereas 1,679 (53%) received chemotherapy in combination with endocrine therapy (chemoendocrine therapy). Overall, adjusted hazard ratios (HRs) associated with chemotherapy tended to be higher in younger patients than in older patients. A total of 1,325 patients (42%) were premenopausal (<50 years). In this subgroup, chemoendocrine therapy was not associated with improved invasive disease-free survival (IDFS; adjusted HR 1.40, 95% CI 0.88–2.24) or overall survival (OS; HR 1.48, 95% CI 0.81–2.69) compared with endocrine therapy alone and was associated with significantly worse distant metastasis-free survival (DMFS; HR 3.46, 95% CI 1.55–7.73). Five-year IDFS, DMFS, and OS were numerically higher among patients treated with endocrine therapy alone. Subgroup analyses demonstrated no survival benefit from chemotherapy across tumor stage, histologic grade, or nodal status, including patients with multiple positive lymph nodes. Conclusions: In this large real-world cohort of premenopausal women with HR-positive, HER2-negative early breast cancer, the addition of chemotherapy to endocrine therapy did not improve survival outcomes. These findings suggest that the observed benefit of chemotherapy in younger patients may largely reflect ovarian function suppression rather than intrinsic chemosensitivity and support a biology-driven, treatment de-escalation approach.