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

Eur J Cancer. 2012 Dec;48(18):3342-54. doi: 10.1016/j.ejca.2012.05.023. Epub 2012 Jul 3.


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+/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.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / radiotherapy
  • Breast Neoplasms / surgery
  • Clinical Trials as Topic / statistics & numerical data
  • Combined Modality Therapy
  • Estrogens*
  • Female
  • Genes, erbB-2*
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Proteins / analysis
  • Neoplasm Staging
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / radiotherapy
  • Neoplasms, Hormone-Dependent / surgery
  • Progesterone*
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Remission Induction
  • Treatment Outcome


  • Biomarkers
  • Estrogens
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2