Clinicopathological significance of androgen receptor expression and tumor infiltrating lymphocytes in triple-negative breast cancer: a retrospective cohort study.
{"title":"Clinicopathological significance of androgen receptor expression and tumor infiltrating lymphocytes in triple-negative breast cancer: a retrospective cohort study.","authors":"Takeshi Ushigusa, Nami Hirakawa, Yuka Kajiura, Atsushi Yoshida, Hideko Yamauchi, Naoki Kanomata","doi":"10.1007/s12282-024-01662-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Overall, 36% (n = 56) of the patients achieved a pathological complete response (pCR). AR<sup>+</sup>/TIL<sup>low</sup> 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<sup>+</sup>/TIL<sup>low</sup>, 15-PGDH-positive, and NAC-resistant. AR<sup>+</sup>/TIL<sup>low</sup> 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<sup>+</sup>/TIL<sup>low</sup> status was not significantly associated with OS or DMFS.</p><p><strong>Conclusions: </strong>AR/TIL classification using pretreatment biopsies identified TNBC subgroups with distinct NAC responses and prognoses. AR<sup>+</sup>/TIL<sup>low</sup> TNBC, including apocrine differentiation cases, were NAC-resistant, highlighting the need for alternative therapies.</p>","PeriodicalId":56083,"journal":{"name":"Breast Cancer","volume":" ","pages":"357-368"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12282-024-01662-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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+/TILlow 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+/TILlow, 15-PGDH-positive, and NAC-resistant. AR+/TILlow 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+/TILlow 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+/TILlow TNBC, including apocrine differentiation cases, were NAC-resistant, highlighting the need for alternative therapies.
期刊介绍:
Breast Cancer, the official journal of the Japanese Breast Cancer Society, publishes articles that contribute to progress in the field, in basic or translational research and also in clinical research, seeking to develop a new focus and new perspectives for all who are concerned with breast cancer. The journal welcomes all original articles describing clinical and epidemiological studies and laboratory investigations regarding breast cancer and related diseases. The journal will consider five types of articles: editorials, review articles, original articles, case reports, and rapid communications. Although editorials and review articles will principally be solicited by the editors, they can also be submitted for peer review, as in the case of original articles. The journal provides the best of up-to-date information on breast cancer, presenting readers with high-impact, original work focusing on pivotal issues.