Tumour molecular subtyping according to hormone receptors and HER2 status defines different pathological complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

Alfonso Sánchez-Muñoz, Ana María García-Tapiador, Esther Martínez-Ortega, Rosario Dueñas-García, Ana Jaén-Morago, Ana Laura Ortega-Granados, Mónica Fernández-Navarro, Capilla de la Torre-Cabrera, Basilio Dueñas, Ana Isabel Rueda, Francisco Morales, César Ramírez-Torosa, María Dolores Martín-Salvago, Pedro Sánchez-Rovira
Clinical & Translational Oncology 2008, 10 (10): 646-53

PURPOSE: To study the role of breast cancer molecular subtypes according to hormone receptors and HER2 status as a predictive factor for pathological complete response (pCR) to neoadjuvant chemotherapy.

PATIENTS AND METHODS: Eligible patients received one of the two chemotherapy schedules every two weeks with prophylactic growth factor support; schedule A: epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2 d1 for 3 cycles followed by a second sequence with paclitaxel (P) 150 mg/ m2-gemcitabine (G) 2500 mg/m2 d1+/-trastuzumab (T) 2 mg/kg/week according to HER2 status (n=73); schedule B: adriamycin (40 mg/m2) d1 plus P (150 mg/m2)-G (2000 mg/m2) d2 for 6 cycles (n=54). Subsequently, patients underwent surgery, radiotherapy and/or adjuvant hormonal therapy according to standard practice.

RESULTS: A total of 127 patients were evaluated. Forty-three patients (33.9%) achieved a pCR (50% in patients with HER2+tumours treated with T). Patients treated with che - motherapy alone (n=107, 18 HER2+) had a pCR of 32% (p=0.068). The pCR rate for patients with triple negative (HR and HER2-) cancers was 58.3%, 39.5% for HER2+ and 5.4% for ER/PR+ and HER2- (p<0.001). No differences in disease-free survival (DFS) were noted as a function of pCR, HER2 and HR status or treatment received (+/-T). However, statistical differences in DFS were observed as a function of whether patients had + or - axillar lymph nodes. Patients with + lymph node disease did worse (3 years DFS of 53.7% vs. 81.5%, p=0.025). Breast-conserving surgery was performed in 77 patients (60.6%).

CONCLUSION: Tumour molecular subtyping defines different pCR to neoadjuvant chemotherapy (NC) but has no impact over DFS in patients with LABC. Although no significant correlation between HER2 status and trastuzumab therapy with pCR was found, probably due to the small number of patients, a favourable trend was observed in the group of HER2+ tumours treated with T.

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