Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy

Abstract

BackgroundPathologic 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. MethodsWe 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. ResultsIn 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+/HR+ [OR 2.6], 38.9% (33.2–44.9%) in HER2+/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. InterpretationThis 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.