Breast and Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Breast Cancer Res Treat. 2012 Apr;132(3):793-805. doi: 10.1007/s10549-011-1554-7. Epub 2011 May 12.
The purpose of the present study was to identify histological surrogate predictive markers of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC). Among 474 patients who received NAC and subsequent surgical therapy for stage II-III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens obtained before NAC were available. As controls, CNB specimens from 42 tumors of the hormone receptor-negative and HER2-positive (HR-/HER2+) subtype and 46 tumors of the hormone receptor-positive and HER2-negative (HR+/HER2-) subtype were also included. Histopathological examination including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis, and immunohistochemical studies for basal markers were performed, and the correlation of these data with pathological therapeutic effect was analyzed. The rates of pCR at the primary site were higher for TNBC (32%) and the HR-/HER2+ subtype (21%) than for the HR+/HER2- subtype (7%) (P = 0.006). Expression of basal markers and p53, histological grade 3, high TIL scores, and apoptosis were more frequent in TNBC and the HR-/HER2+ subtype than in the HR+/HER2- subtype (P = 0.002 for TIL and P < 0.001 for others). In TNBC, the pCR rates of tumors showing a high TIL score and of those showing a high apoptosis score were 37 and 47%, respectively, and significantly higher or tended to be higher than those of the tumors showing a low TIL score and of the tumors showing a low apoptosis score (16 and 27%, respectively, P = 0.05 and 0.10). In a total of 180 breast cancers, the pCR rates of the tumors showing a high TIL score (34%) and of those showing a high apoptosis score (35%) were significantly higher than those of the tumors showing a low TIL score (10%) and those of the tumors showing a low apoptosis score (19%) (P = 0.0001 and 0.04, respectively). Histological grade and basal marker expression were not correlated with pCR. Although the whole analysis was exploratory, the degree of TIL correlated with immune response appear to play a substantial role in the response to NAC in TNBC.
本研究旨在确定三阴性乳腺癌（TNBC）新辅助化疗（NAC）后病理完全缓解（pCR）的组织学替代预测标志物。1999 年至 2007 年间，474 例接受 NAC 及后续手术治疗的 II 期-III 期浸润性乳腺癌患者中，有 102 例（22%）为 TNBC，92 例在 NAC 前获得了核心针活检（CNB）标本。作为对照，还纳入了 42 例激素受体阴性和 HER2 阳性（HR-/HER2+）亚型和 46 例激素受体阳性和 HER2 阴性（HR+/HER2-）肿瘤的 CNB 标本。进行了组织病理学检查，包括肿瘤浸润淋巴细胞（TIL）和肿瘤细胞凋亡，以及基底标志物的免疫组织化学研究，并分析了这些数据与病理治疗效果的相关性。原发部位 pCR 率在 TNBC（32%）和 HR-/HER2+亚型（21%）中高于 HR+/HER2-亚型（7%）（P=0.006）。在 TNBC 和 HR-/HER2+亚型中，基底标志物和 p53 的表达、组织学 3 级、高 TIL 评分和凋亡更为常见（TIL 评分的 P=0.002，其他的 P<0.001）。在 TNBC 中，高 TIL 评分肿瘤和高凋亡评分肿瘤的 pCR 率分别为 37%和 47%，显著高于或有趋势高于低 TIL 评分肿瘤和低凋亡评分肿瘤（分别为 16%和 27%，P=0.05 和 0.10）。在总共 180 例乳腺癌中，高 TIL 评分（34%）和高凋亡评分（35%）肿瘤的 pCR 率明显高于低 TIL 评分（10%）和低凋亡评分（19%）（P=0.0001 和 0.04）。组织学分级和基底标志物表达与 pCR 无关。尽管整个分析是探索性的，但 TIL 程度与免疫反应的相关性似乎在 TNBC 对 NAC 的反应中起着重要作用。
