Triple-Negative Apocrine Carcinoma: Largest Cohort Highlights Unique Biology and Survival Advantage

Background/Objectives: Triple-negative breast cancer (TNBC) is a heterogeneous entity lacking ER, PR, and HER2, with aggressive biology and high recurrence risk. Neoadjuvant chemotherapy (NACT) is the standard of care, and a pathological complete response (pCR) is a surrogate marker for survival. Within TNBC, apocrine differentiation (TNAC) is a distinct subtype, often androgen receptor (AR)-positive, with lower chemosensitivity but a favorable prognosis. Comparative studies of TNAC versus classical TNBC remain limited. This study aimed to define clinical and biological differences between TNAC and non-apocrine TNBC (NA-TNBC), representing the largest TNAC cohort to date. Methods: This retrospective study included 129 non-metastatic TNBC patients treated with NACT and surgery (2010-2020). Patients were classified as TNAC or NA-TNBC. Demographic, clinicopathological, and immunohistochemical data (including Ki-67 and AR) were collected. Tumor-infiltrating lymphocytes (TILs), delta Ki-67, pathological complete response (pCR), and survival outcomes were evaluated. Results: Of 129 TNBC patients, 45 (34.9%) were TNAC. AR positivity occurred in 64.4% of TNACs. TNAC patients were predominantly postmenopausal. pCR rates were significantly lower in TNAC (6.6% vs. 30.9%, p = 0.002). TNACs exhibited lower baseline Ki-67, delta Ki-67, and TIL positivity (13.3% vs. 30%). Despite this, 5-year overall survival was higher in TNAC (86% vs. 78%). Delta Ki-67 > 20% strongly predicted pCR across the cohort (p < 0.001). Carboplatin was rarely used in TNAC (8.3%), but was associated with a higher pCR rate (50% vs. 2.4%, p = 0.018). Conclusions: TNAC represents a biologically distinct TNBC subtype, characterized by low pCR but favorable survival. Recognition of its unique features may guide treatment de-escalation and exploration of AR-targeted therapies. Prospective studies focusing on TNAC are warranted.