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 a serious disease with limited treatment options. We explored the significance of androgen receptor (AR) expression and tumor-infiltrating lymphocytes (TILs) in predicting neoadjuvant chemotherapy (NAC) resistance in TNBC, hypothesizing that AR/TIL classification using pretreatment biopsies can identify NAC-resistant subgroups and improve the understanding of apocrine differentiation.

Methods: This retrospective study included 156 consecutive patients with TNBC treated with NAC. AR immunostaining was defined positive if ≥ 1% of the tumor cell nuclei were stained. Stromal TIL levels were assessed, with high levels defined as ≥ 50%. Apocrine differentiation was detected using an anti-15-PGDH antibody. The pathological response to NAC was evaluated.

Results: Overall, 36% (n = 56) of the patients achieved a pathological complete response (pCR). AR⁺/TIL^low tumors had a high non-pCR rate (76%, 42/55) 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 = 0.013; DMFS: p = 0.0016). All 11 cases with some degree of apocrine differentiation were AR⁺/TIL^low, 15-PGDH-positive, and NAC-resistant. AR⁺/TIL^low status was significantly associated with a high likelihood of non-pCR (OR = 0.26, p = 0.009). Multivariate analysis confirmed pCR as an independent predictor of better prognosis (OS, HR = 0.13, p = 0.006; DMFS, HR = 0.15, p = 0.002), whereas AR⁺/TIL^low status was not significantly associated with OS or DMFS.

Conclusions: AR/TIL classification using pretreatment biopsies identified TNBC subgroups with distinct NAC responses and prognoses. AR⁺/TIL^low TNBC, including apocrine differentiation cases, were NAC-resistant, highlighting the need for alternative therapies.