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 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, 15-PGDH-positive, and NAC-resistant. AR/TIL 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 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 TNBC, including apocrine differentiation cases, were NAC-resistant, highlighting the need for alternative therapies.

COI Statement

Declarations. Conflict of interest: The authors declare that they have no conflicts of interest related to this article. Ethical approval: The study was approved by the Institutional Review Board (22R010). All procedures performed in studies involving human participants adhered to the ethical standards of the institutional research committee, the 1964 Helsinki Declaration, and its later amendments or comparable ethical standards. Patient consent: Informed consent was obtained from all participants in the study.

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