HR-positive breast cancer is the most common subtype, accounting for roughly 65-75% of all breast cancers, in which tumor cells express estrogen receptor (ER) and/or progesterone receptor (PR). ER positivity at or above 1% by immunohistochemistry is considered positive, while contemporary frameworks distinguish ER ≥10% from a low-ER (1-9%) category. PR positivity carries prognostic value, and ER+/PR+ tumors generally show better endocrine therapy response. HR+ tumors are usually HER2-negative; the HR+/HER2- group is further divided into luminal A (low proliferation) and luminal B (high proliferation, elevated Ki-67).
HR+ tumors typically follow a slower clinical course than triple negative or HER2-positive disease but carry greater susceptibility to late recurrences (5-15 years), which is why prolonged adjuvant endocrine therapy (5-10 years) is the standard. In early-stage HR+ disease, multigene assays such as Oncotype DX (21-gene recurrence score), MammaPrint (70 genes), PAM50 (Prosigna), and the Breast Cancer Index help guide adjuvant chemotherapy decisions in node-negative and selected 1-3 node-positive patients. The TAILORx and RxPONDER trials defined which patients benefit from chemotherapy and which can be managed with endocrine therapy alone.
Treatment approach: (1) Early stage — surgery plus radiotherapy plus adjuvant endocrine therapy (with or without chemotherapy). Premenopausal patients receive tamoxifen with or without ovarian suppression (GnRH agonists); high-risk cases use ovarian function suppression plus an aromatase inhibitor (AI). Postmenopausal patients are typically treated with an AI (letrozole, anastrozole, exemestane), with tamoxifen as an alternative. Therapy lasts 5 years, extended to 7-10 years in high-risk cases. (2) High-risk early stage — adjuvant abemaciclib (CDK4/6 inhibitor) for 2 years (monarchE trial); olaparib for BRCA-mutated HER2-negative cases (OlympiA). (3) Metastatic disease — first-line CDK4/6 inhibitor (palbociclib, ribociclib, abemaciclib) plus AI or fulvestrant; second-line fulvestrant plus alpelisib (PIK3CA mutant), elacestrant (ESR1 mutant), or capivasertib (AKT pathway alterations); third-line everolimus plus exemestane; T-DXd in HER2-low cases; sacituzumab govitecan in TROP-2 positive cases; chemotherapy as a last option.