Breast‐Conserving Therapy Versus Mastectomy in Estrogen Receptor–Positive Breast Cancer: A PAM50‐Adjusted Survival Analysis

ABSTRACT Background and Objectives Breast‐conserving therapy (BCT), defined as breast‐conserving surgery followed by radiotherapy, and mastectomy without radiotherapy, are widely used local treatment strategies for breast cancer; however, survival comparisons between these approaches may be confounded by intrinsic tumor biology. The PAM50 gene expression classifier defines biologically distinct molecular subtypes with established prognostic relevance. We evaluated survival outcomes between these surgical approaches in estrogen receptor–positive breast cancer while accounting for intrinsic molecular subtype. Methods Using data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we conducted a retrospective cohort study of estrogen receptor–positive patients treated with either BCT or mastectomy without radiotherapy. Inverse probability of treatment weighting balanced clinicopathologic and treatment‐related variables. PAM50 subtype was excluded from the propensity‐score model but retained in the weighted survival models because of its prognostic relevance. Weighted Cox proportional hazards models evaluated breast cancer–specific survival (BCSS) and overall survival (OS). Results Mastectomy without radiotherapy was associated with worse BCSS (HR 1.59, 95% CI 1.19–2.12, p = 0.002) and worse OS (HR 1.55, 95% CI 1.26–1.91, p < 0.001) compared with BCT. Conclusions BCT was associated with improved breast cancer–specific and overall survival after adjustment for clinicopathologic and molecular factors.