HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer: a meta-analysis of individual patient data
Cette méta-analyse (5 essais randomisés, 6 554 cas) évalue l'intérêt de biomarqueurs basés sur l'amplification des gènes HER2 et TOP2A pour prédire la réponse à un traitement adjuvant à bases d'anthracycline chez des patientes atteintes d'un cancer du sein précoce
Prediction of response to anthracycline-based therapy for breast cancer is challenging. We aimed to assess the value of HER2 and TOP2Aas predictive markers of response to anthracycline-based adjuvant therapy in patients with early breast cancer. We did a meta-analysis of individual patient data from five randomised adjuvant trials that compared anthracycline-based regimens with cyclophosphamide, methotrexate, and fluorouracil (CMF) regimens. We assessed the status ofHER2andTOP2Agenes with fluorescent in-situ hybridisation. Tumour samples were submitted to an external laboratory for validation. We calculated hazard ratios (HR) to compare event-free survival (EFS) and overall survival in patients receiving anthracycline-based treatment with those receiving CMF in twoHER2cohorts (HER2amplified and non-amplified tumours) and in threeTOP2Acohorts (normal, amplified, and deleted tumours). We analysed data for 3452 patients forHER2and 3102 patients forTOP2A. For EFS, HRs were 0·89 (95% CI 0·79?1·01) forHER2non-amplified patients and 0·71 (0·58?0·86) forHER2-amplified patients (pinteraction=0·0485); for overall survival, HRs were 0·91 (95% CI 0·79?1·05) forHER2non-amplified patients and 0·73 (0·59?0·89) forHER2-amplified patients (pinteraction=0·0718). In analysis ofTOP2Astatus, HRs for EFS were 0·88 (0·78?1·00) for normal, 0·63 (0·46?0·87) for deleted, and 0·62 (0·43?0·90) for amplified (pinteraction=0·0513); HRs for overall survival were 0·89 (0·78?1·03) for normal, 0·68 (0·49?0·95) for deleted, and 0·67 (0·46?0·98) for amplified (pinteraction=0·1608). When patients withTOP2A-deleted andTOP2A-amplified tumours were grouped together (altered cohort) and compared with data from patients with normalTOP2Atumours, HRs for EFS were 0·64 (0·50?0·81) for altered and 0·88 (0·78?1·00) for normal (pinteraction=0·0183); HRs for overall survival were 0·67 (0·52?0·86) for altered and 0·89 (0·78?1·03) for normal (pinteraction=0·0455). AlthoughHER2amplification and combinedTOP2Aamplification and deletion may have some value in the prediction of responsiveness to anthracycline-based chemotherapy, our findings do not support the use of anthracyclines only in patients withHER2-amplified orTOP2A-aberrated tumours. Associazione Italiana Ricerca Cancro, Academy of Finland, Belgian Federation Against Cancer, Cancer Research UK, Les Amis de l'Institut Bordet, Scottish Breast Cancer Trials Group, NCIC Clinical Trials Group, Canadian Cancer Society Research Institute, Danish Council for Strategic Research, Pharmacia-Upjohn (now Pfizer), and Abbott Laboratories.
The Lancet Oncology , résumé, 2010