National Surgical Adjuvant Breast and Bowel Project (NSABP), Nova Tower 2, 100 Allegheny Square, Pittsburgh, PA, 15212, USA.
Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 4000 Reservoir Road NW, 120 Building D, Washington, DC, 20057, USA.
Breast Cancer Res Treat. 2019 Nov;178(2):389-399. doi: 10.1007/s10549-019-05398-3. Epub 2019 Aug 19.
NSABP B-41, a phase three randomized trial, evaluated neoadjuvant lapatinib, trastuzumab, or the combination with chemotherapy in patients with HER2-positive operable breast cancer. Though no significant difference in pathologic complete response (pCR) was found among the three arms, pCR was associated with prolonged survival. We analyzed tumor intrinsic subtypes with Prediction Analysis of Microarray 50 in a subset of B-41 patients to determine their value in predicting HER2-targeting benefit.
Pearson's Chi square test and logistic regression were used to compare pCR in the breast and nodes (ypT0/Tis ypN0). Kaplan-Meier estimates and Cox models were used to compare event-free and overall survival among subtypes.
Intrinsic subtypes were determined in 271 baseline core biopsy samples. The pCR rate among patients with HER2-enriched (HER2E) subtype was greater compared to other subtypes combined (120/197, 60.9% versus 19/74, 25.7%; p < 0.001). In multivariate analysis among patients receiving trastuzumab-containing regimens (with clinical factors and HER2E subtype as factors), HER2E subtype was most strongly associated with pCR [OR 8.41 (95% CI 2.52-28.1) p < 0.001]. Patients with HER2E tumors did not benefit more from dual HER2-targeted therapy versus trastuzumab. The pCR rate was higher among HER2E tumors versus other subtypes in both estrogen receptor-positive and -negative tumors (p ≤ 0.001). Higher ESR1 gene expression was associated with lower pCR rate. No association was observed between subtype and long-term outcomes.
Patients with HER2E tumors were most likely to attain pCR versus other subtypes. HER2E subtype represents a favorable marker for predicting HER2-targeting benefit, particularly with trastuzumab-based therapies.
NSABP B-41 是一项三期随机试验，评估了新辅助拉帕替尼、曲妥珠单抗或两者联合化疗在 HER2 阳性可手术乳腺癌患者中的疗效。尽管三组之间病理完全缓解（pCR）无显著差异，但 pCR 与生存延长相关。我们对 B-41 患者的一部分进行了微阵列 50 的预测分析，以确定其在预测曲妥珠单抗治疗获益方面的价值。
采用 Pearson 卡方检验和逻辑回归比较三组患者的乳房和淋巴结 pCR（ypT0/Tis ypN0）。Kaplan-Meier 估计和 Cox 模型用于比较各亚型之间的无事件生存和总生存。
在 271 例基线核心活检样本中确定了内在亚型。HER2 富集（HER2E）亚型患者的 pCR 率高于其他亚型（120/197，60.9%比 19/74，25.7%；p<0.001）。在接受曲妥珠单抗治疗方案的患者中（以临床因素和 HER2E 亚型为因素），多变量分析显示，HER2E 亚型与 pCR 最密切相关[比值比 8.41（95%置信区间 2.52-28.1）p<0.001]。与曲妥珠单抗治疗相比，HER2E 肿瘤患者并未从双重 HER2 靶向治疗中获益更多。HER2E 肿瘤的 pCR 率高于其他亚型，在雌激素受体阳性和阴性肿瘤中均如此（p≤0.001）。ESR1 基因表达较高与较低的 pCR 率相关。亚型与长期结果之间未观察到相关性。
与其他亚型相比，HER2E 肿瘤患者最有可能达到 pCR。HER2E 亚型是预测曲妥珠单抗治疗获益的有利标志物，特别是与基于曲妥珠单抗的治疗方法相关。
