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

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.