Lee Miseon, Lee Ahwon, Yoo Tae-Kyung, Chae Byung Joo, Ahn Sung Gwe, Choi Byung-Ock, Park Woo-Chan, Kim Sung Hun, Lee Jieun, Kang Jun
Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Cancer Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Lab Invest. 2025 Apr 6;105(7):104165. doi: 10.1016/j.labinv.2025.104165.
This study aimed to evaluate the clinicopathologic and genomic characteristics of triple-negative breast cancer subclassification. Triple-negative breast cancer was classified into the luminal androgen receptor (LAR) subtype and the tumor-infiltrating lymphocytes (TILs) groups of the non-LAR subtype-lymphocyte predominant (LP), lymphocyte intermediate, and lymphocyte depleted-based on androgen receptor immunohistochemistry and TILs. Clinicopathologic and genomic characteristics were evaluated for these triple-negative breast cancer subclasses. The LP group was associated with a histologic type of carcinoma with medullary features, a higher tumor mutation burden, and increased APOBEC activity, indicative of APOBEC-driven hypermutation. The LAR subtype was characterized by a higher prevalence of PIK3CA mutations, lower homologous recombination deficiency scores, and associations with histologic types of invasive lobular carcinoma, and carcinoma with apocrine differentiation. This study demonstrated the distinct clinicopathologic and genomic characteristics of triple-negative breast cancer subclassifications. APOBEC activity-related hypermutation is a defining characteristic of the LP group.
本研究旨在评估三阴性乳腺癌亚分类的临床病理和基因组特征。基于雄激素受体免疫组化和肿瘤浸润淋巴细胞（TILs），将三阴性乳腺癌分为腔面雄激素受体（LAR）亚型和非LAR亚型的TILs组，后者包括淋巴细胞为主型（LP）、淋巴细胞中间型和淋巴细胞减少型。对这些三阴性乳腺癌亚类的临床病理和基因组特征进行了评估。LP组与具有髓样特征的癌组织学类型、较高的肿瘤突变负荷和增加的载脂蛋白B mRNA编辑酶催化多肽样3（APOBEC）活性相关，提示APOBEC驱动的高突变。LAR亚型的特征是磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）突变发生率较高；同源重组缺陷评分较低；与浸润性小叶癌和大汗腺分化癌的组织学类型相关。本研究证明了三阴性乳腺癌亚分类具有独特的临床病理和基因组特征。APOBEC活性相关的高突变是LP组的一个决定性特征。
