Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy
Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy
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DOI：
10.1016/j.ejca.2012.05.023
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发表时间：
2012-12-01
影响因子：
8.4
通讯作者：
Mamounas, Eleftherios
中科院分区：
文献类型：
--
作者：
Houssami, Nehmat;Macaskill, Petra;Mamounas, Eleftherios
背景：病理完全缓解（pCR）是乳腺癌新辅助化疗（NAC）预后的替代终点。我们的目的是报告的肿瘤亚型的受试者实现pCR（pCR%）的比例的汇总估计，并确定是否亚型与pCR独立相关，在一项研究水平的荟萃analysis.Methods：我们系统地确定了NAC研究报告的pCR数据根据肿瘤亚型，使用预定义的资格标准。提取描述性、定性和定量数据。随机效应logistic荟萃回归检查了pCR%是否与亚型相关，使用模型1的3个类别[激素受体阳性（HR+/HER 2-）、HER 2阳性（HER 2+）、三阴性（ER-/PR-/HER 2-）]和模型2的4个类别[HER 2+进一步分类为HER 2 +/HR+和HER 2 +/HR-]定义。结果：在模型1中，基于来自30项合格研究的11，695例受试者，总体合并pCR%为18.9%（16.6-21.5%），模型2（20项研究，8095例受试者）汇总pCR%为18.5%（16.2-21.1%）;两种模型中肿瘤亚型均与pCR%相关（P < 0.0001）。亚型特异性pCR%（模型2）为：8.3%（6.7-10.2%）HR+/HER 2-[OR 1/参照]，18.7%（15.0-23.1%），HER 2垂直条/HR垂直条[OR 2.6]，百分之三十八点九（33.2-44.9%），HER 2垂直条/HR-[OR 7.1]和31.1%三阴性组（26.5-36.1%）[OR 5.0];与三阴性亚型相比，HER 2 +/HR-的pCR%显著更高，然而，当从模型中排除使用HER 2导向的NAC治疗的研究时，这些亚型的pCR%非常相似（两种亚型的OR = 5.0）。敏感性分析（不包括未知亚型），也不调整相关的协变量，实质上改变了我们的发现。解释：这项荟萃分析提供了乳腺癌亚型和pCR之间独立关联的证据;三阴性和HER 2 +/HR-亚型的pCR几率最高，有证据表明，通过纳入HER 2导向的NAC治疗，对后一种亚型实现pCR具有影响作用。(C)2012爱思唯尔有限公司保留所有权利。
Background: Pathologic complete response (pCR) is a surrogate end-point for prognosis in neoadjuvant chemotherapy (NAC) for breast cancer. We aimed to report summary estimates of the proportion of subjects achieving pCR (pCR%) by tumour subtype, and to determine whether subtype was independently associated with pCR, in a study-level meta-analysis.Methods: We systematically identified NAC studies reporting pCR data according to tumour subtype, using predefined eligibility criteria. Descriptive, qualitative and quantitative data were extracted. Random effects logistic meta-regression examined whether pCR% was associated with subtype, defined using three categories for model 1 [hormone receptor positive (HR+/HER2-), HER2 positive (HER2+), triple negative (ER-/PR-/HER2-)] and 4 categories for model 2 [HER2+ further classified as HER2+/HR+ and HER2+/HR-]. Subtype-specific odds ratios (OR) were calculated and were adjusted for covariates associated with pCR in our data.Results: In model 1, based on 11,695 subjects from 30 eligible studies, overall pooled pCR% was 18.9% (16.6-21.5%), and in model 2 (20 studies, 8095 subjects) pooled pCR% was 18.5% (16.2-21.1%); tumour subtype was associated with pCR% (P < 0.0001) in both models. Subtype-specific pCR% (model 2) was: 8.3% (6.7-10.2%) in HR+/HER2-[OR 1/referent], 18.7% (15.0-23.1%) in HER2 vertical bar /HR vertical bar [OR 2.6], 38.9% (33.2-44.9%) in HER2 vertical bar /HR-[OR 7.1] and 31.1% (26.5-36.1%) in triple negative [OR 5.0]; pCR% was significantly higher for the HER2+/HR-compared with the triple negative subtype, however pCR% was very similar for these subtypes (and OR = 5.0 both subtypes) when studies using HER2-directed therapy with NAC were excluded from the model. Neither sensitivity analysis (excluding unknown subtypes), nor adjustment for associated covariates, substantially altered our findings.Interpretation: This meta-analysis provides evidence of an independent association between breast cancer subtype and pCR; odds of pCR were highest for the triple negative and HER2+/HR-subtypes, with evidence of an influential effect on achieving pCR in the latter subtype through inclusion of HER2-directed therapy with NAC. (C) 2012 Elsevier Ltd. All rights reserved.