Conundrum of low hormone receptor-positive breast cancer

Hormone receptor-low (HR-low) breast cancer, defined by ASCO/CAP guidelines as displaying 1% to 10% estrogen and/or progesterone receptor expression, presents a significant clinical dilemma. Accounting for approximately 7% of cases, this cohort is characteristically associated with younger patients, high-grade tumors, elevated Ki-67 indices, and distinct biological heterogeneity. Clinically, HR-low tumors exhibit a profound paradox: while standard guidelines recommend managing them as luminal-type disease, their molecular features, high tumor-infiltrating lymphocyte counts, and PD-L1 expression profiles closely mirror basal-like, triple-negative breast cancer (TNBC). Pathological identification remains heavily confounded by subjective interpretation and preanalytical testing variations. Therapeutic outcomes further highlight this dual identity; HR-low tumors achieve high pathological complete response (pCR) rates to neoadjuvant chemotherapy and immunotherapy protocols (such as the KEYNOTE-522 regimen) that are comparable to TNBC, yet they experience worse overall survival than strongly HR-positive cancers. Conversely, large-scale data confirms a distinct overall survival benefit from adjuvant endocrine therapy, though extending this treatment beyond three years yields no additional survival advantage. Ongoing clinical uncertainty persists regarding their inclusion in major trials. Managing HR-low breast cancer requires transitioning away from rigid immunohistochemical thresholds toward a nuanced, personalized approach utilizing molecular profiling to accurately identify patient subsets most likely to benefit from targeted endocrine or immunotherapeutic strategies.