Scholarlink

Background <p>Previous studies often combined double hormone receptor-positive (dHR +) and single HR-positive (sHR +) tumors, thus not accounting for the distinct characteristics of sHR + , particularly in the neoadjuvant setting. Moreover, adding immunotherapy to cytotoxic chemotherapy has shown encouraging efficacy in certain HR-positive early breast cancers. This study sought to assess pathological complete response (pCR) and survival outcomes in sHR + /HER2- breast cancer after neoadjuvant chemotherapy, while also investigating its specific biological traits and immune profile.</p> Methods <p>Clinical data were sourced from the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS, <i>n</i> = 1049), and the Surveillance, Epidemiology, and End Results (SEER, <i>n</i> = 21,092) database to examine neoadjuvant chemosensitivity and survival outcomes. Additionally, clinicopathological and subtype data from CHCAMS, SEER, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, <i>n</i> = 1052), and Fudan University Shanghai Cancer Center (FUSCC, <i>n</i> = 570) were analyzed to identify biological features that correlate with pCR rates and prognosis in sHR + /HER2- breast cancer. Further genomic and transcriptomic data from METABRIC, The Cancer Genome Atlas (TCGA, <i>n</i> = 741), and MSK-IMPCAT (<i>n</i> = 1535) were reviewed to uncover their potential links with endocrine and immunotherapy responses.</p> Results <p>In comparison to dHR + (ER + and PR +)/HER2- breast cancer, sHR + (ER + /PR- or ER-/PR +)/HER2- breast cancer displayed a higher pCR rate (20.2% vs. 3.2%, <i>P</i> &lt; 0.001), but considerably worse survival (hazard ratio, 2.97; 95% confidence interval, 1.62–5.43, <i>P</i> &lt; 0.001) within the CHCAMS neoadjuvant cohort. Clinically, sHR + /HER2- tumors were associated with higher histological grades and proliferation rates compared to dHR + /HER2- tumors, along with a greater rate of HR-low positivity (50.9% vs. 3.0%, <i>P</i> &lt; 0.001) in primary tumors and a tendency to transition to triple-negative tumors in residual disease (42.7% vs. 1.8%, <i>P</i> &lt; 0.001). Furthermore, sHR + /HER2- breast cancers demonstrated lower endocrine sensitivity scores, with about 20% classified as PAM50-defined basal-like subtype. Immunologically, sHR + /HER2- tumors had elevated tumor mutation burden (TMB), higher expression of immune checkpoint genes (e.g., PD-1, PD-L1, CTLA4), and greater infiltration by tumor-infiltrating lymphocytes (TILs), particularly CD8 + T cells, than dHR + /HER2- tumors.</p> Conclusion <p>Compared to dHR + /HER2- breast cancer, sHR + /HER2- cases showed a relative sensitivity to neoadjuvant chemotherapy but poorer prognosis. The immune-activated phenotype of sHR + /HER2- breast cancer indicates that it may benefit from immunotherapy approaches, but these findings warrant validation in prospective studies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pathological complete response and survival outcomes in single hormone receptor-positive/HER2-negative breast cancer after neoadjuvant chemotherapy and its intrinsic biological features and immune landscape

  • 期刊论文

  • 发表日期：

    2025年9月17日

查看全文
  • Lei Ji,
  • Xi Chen,
  • Hongwei Lyu,
  • Ge Song,
  • Min Xiao,
  • Qing Li,
  • Jiayu Wang,
  • Ying Fan,
  • Yang Luo,
  • Qiao Li,
  • Shanshan Chen,
  • Fei Ma,
  • Binghe Xu,
  • Pin Zhang

摘要

Background

Previous studies often combined double hormone receptor-positive (dHR +) and single HR-positive (sHR +) tumors, thus not accounting for the distinct characteristics of sHR + , particularly in the neoadjuvant setting. Moreover, adding immunotherapy to cytotoxic chemotherapy has shown encouraging efficacy in certain HR-positive early breast cancers. This study sought to assess pathological complete response (pCR) and survival outcomes in sHR + /HER2- breast cancer after neoadjuvant chemotherapy, while also investigating its specific biological traits and immune profile.

Methods

Clinical data were sourced from the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS, n = 1049), and the Surveillance, Epidemiology, and End Results (SEER, n = 21,092) database to examine neoadjuvant chemosensitivity and survival outcomes. Additionally, clinicopathological and subtype data from CHCAMS, SEER, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1052), and Fudan University Shanghai Cancer Center (FUSCC, n = 570) were analyzed to identify biological features that correlate with pCR rates and prognosis in sHR + /HER2- breast cancer. Further genomic and transcriptomic data from METABRIC, The Cancer Genome Atlas (TCGA, n = 741), and MSK-IMPCAT (n = 1535) were reviewed to uncover their potential links with endocrine and immunotherapy responses.

Results

In comparison to dHR + (ER + and PR +)/HER2- breast cancer, sHR + (ER + /PR- or ER-/PR +)/HER2- breast cancer displayed a higher pCR rate (20.2% vs. 3.2%, P < 0.001), but considerably worse survival (hazard ratio, 2.97; 95% confidence interval, 1.62–5.43, P < 0.001) within the CHCAMS neoadjuvant cohort. Clinically, sHR + /HER2- tumors were associated with higher histological grades and proliferation rates compared to dHR + /HER2- tumors, along with a greater rate of HR-low positivity (50.9% vs. 3.0%, P < 0.001) in primary tumors and a tendency to transition to triple-negative tumors in residual disease (42.7% vs. 1.8%, P < 0.001). Furthermore, sHR + /HER2- breast cancers demonstrated lower endocrine sensitivity scores, with about 20% classified as PAM50-defined basal-like subtype. Immunologically, sHR + /HER2- tumors had elevated tumor mutation burden (TMB), higher expression of immune checkpoint genes (e.g., PD-1, PD-L1, CTLA4), and greater infiltration by tumor-infiltrating lymphocytes (TILs), particularly CD8 + T cells, than dHR + /HER2- tumors.

Conclusion

Compared to dHR + /HER2- breast cancer, sHR + /HER2- cases showed a relative sensitivity to neoadjuvant chemotherapy but poorer prognosis. The immune-activated phenotype of sHR + /HER2- breast cancer indicates that it may benefit from immunotherapy approaches, but these findings warrant validation in prospective studies.