Departments of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Breast Cancer Res Treat. 2012 Feb;131(3):827-36. doi: 10.1007/s10549-011-1488-0. Epub 2011 Apr 7.
A pathological complete remission (pCR) is rarely achieved by neoadjuvant chemotherapy in estrogen receptor-positive (ER+) HER2-negative (HER2-) tumors. Therefore, its use might be questionable in specific groups of this tumor type. To select which patients benefit and which could be spared neoadjuvant chemotherapy, we tested standard pathology and molecular markers in ER+ HER2- breast tumors. Pretreatment biopsies were available from 211 ER+ HER2- tumors, who had been treated with neoadjuvant chemotherapy (adriamycin/cyclophosphamide). mRNA expression data were available for 132 tumors. We determined progesterone receptor expression (PR), endocrine sensitivity, HER2 expression, histology, proliferation, and molecular subtypes. We correlated these data to chemotherapy response using pCR rates and the previously published neoadjuvant response index (NRI). PR-negative tumors (n = 65, 30.8%) and luminal B type tumors (n = 43, 20.4%) responded significantly better to chemotherapy than other tumors. These associations remained significant in multivariate analysis. However, even in the subgroup of patients with the lowest response rate, comprising tumors that had both a positive-PR expression and the luminal A subtype (n = 58, 44%), the majority of the patients had downstaging because of chemotherapy. For histology (lobular vs. ductal), endocrine sensitivity, and proliferation, no associations with chemotherapy response were observed. Gene expression array analysis resulted in 28 significant genes (FDR < 0.1). PR expression and luminal B status are associated with a better response to neoadjuvant chemotherapy. However, both markers had only weak response predictive power, and it was not possible to identify a subgroup with no or only minimal chemotherapy benefit. Therefore, the decision to refrain from neoadjuvant chemotherapy to ER+ HER2- breast tumors should not be based on predictive markers, but exclusively on estimates of prognosis.
在雌激素受体阳性（ER+）、HER2 阴性（HER2-）肿瘤中，新辅助化疗很少能达到病理完全缓解（pCR）。因此，在这种肿瘤类型的某些特定人群中，其使用可能存在疑问。为了选择哪些患者受益，哪些患者可以避免新辅助化疗，我们在 ER+HER2-乳腺癌肿瘤中测试了标准病理学和分子标志物。211 例接受新辅助化疗（阿霉素/环磷酰胺）的 ER+HER2-肿瘤患者可获得预处理活检。132 例肿瘤有 mRNA 表达数据。我们确定了孕激素受体表达（PR）、内分泌敏感性、HER2 表达、组织学、增殖和分子亚型。我们将这些数据与化疗反应相关联，使用 pCR 率和先前发表的新辅助反应指数（NRI）。PR 阴性肿瘤（n=65，30.8%）和 luminal B 型肿瘤（n=43，20.4%）对化疗的反应明显优于其他肿瘤。这些关联在多变量分析中仍然显著。然而，即使在包含 PR 表达阳性和 luminal A 亚型的肿瘤（n=58，44%）这一反应率最低的亚组中，由于化疗，大多数患者仍有降级。对于组织学（小叶与导管）、内分泌敏感性和增殖，未观察到与化疗反应相关联。基因表达阵列分析产生了 28 个显著基因（FDR<0.1）。PR 表达和 luminal B 状态与新辅助化疗的更好反应相关联。然而，这两个标志物的反应预测能力都很弱，无法确定没有或仅有最小化疗获益的亚组。因此，决定是否对 ER+HER2-乳腺癌肿瘤放弃新辅助化疗不应基于预测标志物，而应仅基于预后估计。
