{"title":"三阴性乳腺癌中雄激素受体表达和肿瘤浸润淋巴细胞的临床病理意义:一项回顾性队列研究","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":"{\"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}","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
摘要
背景:三阴性乳腺癌(TNBC)是一种严重的疾病,治疗方案有限。我们探讨了雄激素受体(AR)表达和肿瘤浸润淋巴细胞(TILs)在预测TNBC新辅助化疗(NAC)耐药中的意义,假设使用预处理活检进行AR/TIL分类可以识别NAC耐药亚组,并提高对顶泌分化的理解。方法:本回顾性研究纳入156例连续接受NAC治疗的TNBC患者。≥1%的肿瘤细胞核染色为AR免疫染色阳性。评估基质TIL水平,高水平定义为≥50%。用抗15- pgdh抗体检测大汗液分化。评价NAC的病理反应。结果:总体而言,36% (n = 56)的患者实现了病理完全缓解(pCR)。AR+/TILlow肿瘤非pcr率高(76%,42/55),对NAC耐药。Kaplan-Meier图显示,4个AR/TIL亚组的总生存期(OS)和远端无转移生存期(DMFS)存在显著差异(OS: p = 0.013;DMFS: p = 0.0016)。11例有不同程度大汗液分化的患者均为AR+/TILlow, 15- pgdh阳性,耐nac。AR+/TILlow状态与非pcr的高可能性显著相关(OR = 0.26, p = 0.009)。多因素分析证实pCR是预后较好的独立预测因子(OS, HR = 0.13, p = 0.006;DMFS, HR = 0.15, p = 0.002),而AR+/TILlow状态与OS或DMFS无显著相关。结论:采用预处理活检进行AR/TIL分类,确定了具有不同NAC反应和预后的TNBC亚组。AR+/TILlow TNBC,包括大汗液分化病例,对nac耐药,强调需要替代治疗。
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+/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.