From the Departments of Pathology (Zeng, Edelweiss, Ross, Xu, Brogi, D'Alfonso), Memorial Sloan Kettering Cancer Center, New York, New York.
Breast Surgical Oncology (Moo), Memorial Sloan Kettering Cancer Center, New York, New York.
Arch Pathol Lab Med. 2021 Jun 1;145(6):728-735. doi: 10.5858/arpa.2020-0293-OA.
CONTEXT.—: It is unclear whether HER2+ tumors expressing both estrogen receptor (ER) and progesterone receptor (PR), that is, triple-positive breast carcinomas (TPBCs), show unique morphologic and clinical features and response to neoadjuvant chemotherapy (NAC).
OBJECTIVE.—: To study the morphologic and immunohistochemical features of TPBCs from patients who underwent NAC.
DESIGN.—: We retrospectively reviewed core biopsy and post-NAC slides of 85 TPBCs. H-scores were calculated for ER and PR. HER2 slides and fluorescence in situ hybridization (FISH) reports were reviewed. Residual cancer burden was calculated for post-NAC specimens.
RESULTS.—: Eighty-one of the 85 tumors (95.3%) showed ductal histology, 3 (3.5%) were invasive lobular carcinomas, and 1 (1.2%) showed mixed ductal and lobular features. A subset showed mucinous (n = 7, 8.2%), apocrine (n = 5, 5.9%), and/or micropapillary (n = 4, 4.7%) differentiation. Fifty-four TPBCs (63.5%) showed high ER expression (H-score >200), including 27 (31.8%) with high expression of ER and PR. Fifty-two tumors (61.1%) showed HER2 3+ staining. Mean HER2/CEP17 ratio by FISH was 3.6 (range, 2-12.2) and mean HER2 signals per cell was 8 (range, 3.7-30.4). Pathologic complete response (pCR) rate was 35.3% (30 of 85). HER2 3+ staining was the only significant predictor of pCR on multivariate analysis (odds ratio = 9.215; 95% CI, 2.401-35.371; P < .001). The ER/PR expression did not correlate with response to therapy.
CONCLUSIONS.—: TPBCs are heterogeneous with some showing mucinous, lobular, or micropapillary differentiation. The pCR rate of TPBCs is similar to that reported for ER+/PR-/HER2+ tumors. HER2 overexpression by IHC was associated with significantly better response to therapy and may help select patients for treatment in the neoadjuvant setting.
HER2+ 肿瘤同时表达雌激素受体（ER）和孕激素受体（PR），即三阳性乳腺癌（TPBC），其形态学和临床特征以及对新辅助化疗（NAC）的反应是否具有独特性尚不清楚。
研究接受 NAC 的 TPBC 患者的形态学和免疫组织化学特征。
我们回顾性分析了 85 例 TPBC 患者的核心活检和 NAC 后切片。计算 ER 和 PR 的 H 评分。回顾 HER2 切片和荧光原位杂交（FISH）报告。计算 NAC 后标本的残留癌负荷。
85 例肿瘤中有 81 例（95.3%）为导管组织学，3 例（3.5%）为浸润性小叶癌，1 例（1.2%）为混合导管和小叶特征。一部分表现为黏液（n = 7，8.2%）、大汗腺（n = 5，5.9%）和/或微乳头状（n = 4，4.7%）分化。54 例 TPBC（63.5%）表现出高 ER 表达（H 评分>200），其中 27 例（31.8%）表现出 ER 和 PR 高表达。52 例肿瘤（61.1%）表现出 HER2 3+染色。FISH 检测的平均 HER2/CEP17 比值为 3.6（范围，2-12.2），平均每个细胞的 HER2 信号为 8（范围，3.7-30.4）。病理完全缓解（pCR）率为 35.3%（30/85）。多变量分析显示，HER2 3+染色是 pCR 的唯一显著预测因素（比值比=9.215；95%CI，2.401-35.371；P<0.001）。ER/PR 表达与治疗反应无关。
TPBC 具有异质性，一些表现为黏液、小叶或微乳头状分化。TPBC 的 pCR 率与报道的 ER+/PR-/HER2+肿瘤相似。HER2 通过 IHC 的过表达与治疗反应显著改善相关，可能有助于在新辅助治疗中选择合适的治疗患者。
