Department of Pathology, the First Affinity Hospital of the Air Force Military Medical University, Xi'an, Shaan Xi Province, 710032, China.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, 68105, NE, USA.
Pathol Res Pract. 2021 Dec;228:153677. doi: 10.1016/j.prp.2021.153677. Epub 2021 Oct 30.
HER2-positive breast carcinomas are all treated with first-line anti-HER2 therapy. However, immunohistochemical and molecular profiling demonstrates significant heterogeneity among HER2-positive carcinomas. Basal-like HER2-positive breast carcinomas are poorly differentiated from pure HER2-positive breast carcinomas.
Seventy-five patients with HER2-positive, ER- and PR-negative breast carcinomas who received anti-HER2 based neoadjuvant therapy were retrospectively analyzed. Thirty-seven cases were classified as basal-like HER2-positive breast carcinoma with any positivity for CK5/6, and thirty-eight cases were classified as pure HER2-positive breast carcinoma with completely negativity for CK5/6. The clinicopathological features and tumor responses after neoadjuvant therapy and outcomes were analyzed.
Compared to non-basal HER2-positive breast carcinoma, basal-like HER2-positive breast carcinoma showed distinctive histologic features including poor differentiation and syncytial tumor cells with pushing, invasive borders and a significantly higher proportion of apocrine metaplasia. They also demonstrated significantly higher histologic grade; 18/37 (48.6%) of basal-like carcinomas were grade 3, whereas only 5/38 (13.2%) of non-basal carcinomas were grade 3 (p = 0.001), Furthermore, basal-like HER2-positive breast carcinomas were more likely to be positive or completely negative for p53 (p = 0.009), and demonstrated a higher percentage of TP53 mutation (p = 0.17). These tumors were less responsive to anti-HER2 based neoadjuvant therapy, with Miller-Payne grades 1-3 higher than pure HER2-positive breast carcinoma (25/37 [67.6%] vs 16/38 [42.1%]), and the percentage of grade 4-5 was lower (12/37 [32.4%] vs 22/38 [57.9%]; p = 0.027).
Basal-like HER2-positive breast carcinoma has distinctive clinicopathological features and less histologic tumor response after neoadjuvant therapy. There is urgent need to recognize basal-like HER2-positive breast carcinoma to be treated precisely.
人表皮生长因子受体 2（HER2）阳性乳腺癌均接受一线抗 HER2 治疗。然而，免疫组织化学和分子分析显示 HER2 阳性乳腺癌存在显著异质性。基底样 HER2 阳性乳腺癌与纯 HER2 阳性乳腺癌相比分化较差。
回顾性分析了 75 例接受抗 HER2 新辅助治疗的 HER2 阳性、雌激素受体（ER）和孕激素受体（PR）阴性乳腺癌患者。37 例被归类为基底样 HER2 阳性乳腺癌，任何 CK5/6 阳性；38 例被归类为纯 HER2 阳性乳腺癌，CK5/6 完全阴性。分析新辅助治疗后的临床病理特征、肿瘤反应和治疗结局。
与非基底型 HER2 阳性乳腺癌相比，基底样 HER2 阳性乳腺癌具有独特的组织学特征，包括分化差、合体样肿瘤细胞呈推进性、浸润性边界，以及更高比例的大汗腺化生。它们的组织学分级也显著较高；37 例基底样乳腺癌中 18 例（48.6%）为 3 级，而 38 例非基底样乳腺癌中仅 5 例（13.2%）为 3 级（p=0.001）。此外，基底样 HER2 阳性乳腺癌更可能为 p53 阳性或完全阴性（p=0.009），并且 TP53 突变的比例更高（p=0.17）。这些肿瘤对基于抗 HER2 的新辅助治疗反应较差，Miller-Payne 分级 1-3 高于纯 HER2 阳性乳腺癌（25/37[67.6%] vs 16/38[42.1%]），而 4-5 级的比例较低（12/37[32.4%] vs 22/38[57.9%]；p=0.027）。
基底样 HER2 阳性乳腺癌具有独特的临床病理特征，新辅助治疗后组织学肿瘤反应较差。迫切需要认识到基底样 HER2 阳性乳腺癌并进行精准治疗。
