HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data

摘要: Summary Background Prediction of response to anthracycline-based therapy for breast cancer is challenging. We aimed assess the value HER2 and TOP2A as predictive markers adjuvant in patients with early cancer. Methods did a meta-analysis individual patient data from five randomised trials that compared regimens cyclophosphamide, methotrexate, fluorouracil (CMF) regimens. assessed status genes fluorescent in-situ hybridisation. Tumour samples were submitted an external laboratory validation. calculated hazard ratios (HR) compare event-free survival (EFS) overall receiving treatment those CMF two cohorts ( amplified non-amplified tumours) three (normal, amplified, deleted tumours). Findings analysed 3452 3102 . For EFS, HRs 0·89 (95% CI 0·79–1·01) 0·71 (0·58–0·86) -amplified (p interaction =0·0485); survival, 0·91 0·79–1·05) 0·73 (0·59–0·89) =0·0718). In analysis status, EFS 0·88 (0·78–1·00) normal, 0·63 (0·46–0·87) deleted, 0·62 (0·43–0·90) =0·0513); (0·78–1·03) 0·68 (0·49–0·95) 0·67 (0·46–0·98) =0·1608). When -deleted tumours grouped together (altered cohort) normal tumours, 0·64 (0·50–0·81) altered =0·0183); (0·52–0·86) =0·0455). Interpretation Although amplification combined deletion may have some prediction responsiveness chemotherapy, our findings do not support use anthracyclines only or -aberrated tumours. Funding Associazione Italiana Ricerca Cancro, Academy Finland, Belgian Federation Against Cancer, Cancer Research UK, Les Amis de l'Institut Bordet, Scottish Breast Trials Group, NCIC Clinical Canadian Society Institute, Danish Council Strategic Research, Pharmacia-Upjohn (now Pfizer), Abbott Laboratories.