Clinicopathological significance of androgen receptor expression and tumor infiltrating lymphocytes in triple-negative breast cancer: a retrospective cohort study

Background Triple-negative breast cancer (TNBC) is aggressive and has limited treatment options. This study explored the clinical significance of androgen receptor (AR) expression and tumor-infiltrating lymphocytes (TILs) in predicting neoadjuvant chemotherapy (NAC) resistance in TNBC, hypothesizing that AR/TIL classification can identify NAC-resistant subgroups and improve the understanding of apocrine differentiation. Methods This retrospective study included 96 consecutive patients with TNBC treated with NAC. AR immunostaining was defined as positive if ≥ 1% of the tumor cell nuclei were stained and stromal TIL levels were assessed, with high levels defined as ≥ 50%. Apocrine differentiation was detected using an anti-15-PGDH antibody. Pathological response to NAC was also evaluated. Results Overall, 38% (n = 36) of the patients achieved pathological complete response (pCR). AR ⁺ /TIL ^low tumors had a significantly higher non-pCR rate (79%, 23 of 29 patients) and were resistant to NAC. Kaplan-Meier plots showed significant differences in overall survival (OS) and distant metastasis-free survival (DMFS) among the four AR/TIL subgroups (OS, P = 0.047; DMFS, P = 0.0053). All seven cases with some degree of apocrine differentiation were AR ⁺ /TIL ^low , 15-PGDH-positive, and showed NAC resistance. AR ⁺ /TIL ^low status as an independent predictor of non-pCR (OR 0.32, P = 0.032). pCR predicted better prognosis (OS, HR 0.14, P = 0.010; DMFS, HR 0.11, P = 0.003), whereas AR ⁺ /TIL ^low status was not significantly associated with OS or DMFS. Conclusions AR/TIL classification was used to identify TNBC subgroups with distinct NAC responses and prognoses. AR ⁺ /TIL ^low TNBC, including cases with some degree of apocrine differentiation, are NAC-resistant, suggesting the need for alternative therapies.