A multicenter randomized phase II study of sequential epirubicin/cyclophosphamide followed by docetaxel with or without celecoxib or trastuzumab according to HER2 status, as primary chemotherapy for localized invasive breast cancer patients

• DOI: 10.1007/s10549-010-0939-3
• Publication Date: 2010-05-17T04:35:51Z
• Authors: Jean-Yves Pierga; Suzette Delaloge; Marc Espié; Etienne Brain; Brigitte Sigal-Za...; Marie-Christine M...; Philippe Bertheau; Jean Marc Guinebr...; Marc Spielmann; Alexia Savignoni; Michel Marty
• Keywords: Epirubicin; Celecoxib

Abstract Purpose: To assess anti tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the randomized addition of celecoxib In Her2-ve patients or trastuzumab in Her2+ve patients versus no additional treatment, in terms of pathological complete response (pCR), defined as absence of residual invasive breast carcinoma and of nodal involvement.Patients and methods: 340 patients with stage II and III breast adenocarcinoma, with tumors ineligible for breast conservative surgery received 8 sequential 3 weekly cycles with epirubicin (75mg/m2)-cyclophosphamide (750mg/m2) for 4 cycles followed by docetaxel (100 mg/m2) for 4 cycles. According to HER2 status (IHC + FISH) they were randomized to receive together with docetaxel, in HER2 negative group (220 patients) celecoxib 800 mg/day during cycles 5-8 or no additional treatment and in HER2 positive group (120 patients) trastuzumab (8mg/kg then 6mg/kg) infused together with docetaxel or no additional treatment. All patients except eight with HER2+ tumor received adjuvant trastuzumab for a cumulative duration of 12 months.Results: In the HER2 negative group, pCR (grade 1 and 2 of Chevallier's classification) was observed in 11.5% and 13% of patients treated without and with neoadjuvant Celecoxib respectively. In the HER2+ group, pCR rate reached 26% in those having received neoadjuvant trastuzumab versus 19% in the others. There was no cardiac toxicity and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%.Conclusion: It is the first report on the effect of the addition of celecoxib to chemotherapy in neoadjuvant setting in breast cancer, showing that celecoxib does not improve the pCR rate. Addition of trastuzumab does, yet not to the extent reported with a protracted co-administration before surgery. Expression of hormonal receptors appears to be the major prognosticator for pCR. Molecular studies of gene expression profiling should allow improving such prediction.Supported by PHRC AOM/2OO2/02117, Pfizer inc., Roche, sanofi-aventis.ISRCTN10059974 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5054.