Women with large (≥3cm) and locally advanced breast cancers (T3, 4, N1, 2, M0) receiving neoadjuvant chemotherapy (NAC: cyclophosphamide, doxorubicin, docetaxel): addition of capecitabine improves 4-year disease-free survival.

Jennifer Eremin,Ged Cowley,Leslie G Walker,Oleg Eremin,Monika Stovickova,Elisabeth Murray

doi:10.1186/2193-1801-4-9

Abstract

PurposeTo determine whether capecitabine (X), combined with docetaxel (T) following doxorubicin (A) and cyclophosphamide (C), enhanced the pathological complete response (pCR) in the breast and axillary lymph nodes (ALNs) of women with large or locally advanced breast cancers (LLABCs) improving outcome, and the effect on quality of life (QoL).Patients and methods117 women were enrolled, 112 randomised to 2 cycles of AC (60 mg/m2, 600 mg/m2) given 3 weekly. Tumour responses were assessed by magnetic resonance mammography. Responders (n = 77) received 2 further cycles of AC and were randomised to 4 cycles of T (100 mg/m2) (Group A) or T (75 mg/m2) and X (2000 mg/m2/day), day one to 14 of each 3 weekly cycle (Group B). Non-responders (n = 35) were randomised to 6 cycles of T (Group C) or T + X (Group D). QoL questionnaires were completed at each chemotherapy visit. Pathological responses were evaluated using established criteria.ResultsThe groups were comparable in patient and tumour characteristics (79.5% T2, 85.7% ductal, 73.2% ER +ve, 22.3% HER2 +ve, 42% involved ALNs). Overall breast pCR was 27.1%, Groups A + C versus B + D (p = 0.446). ALN +ve pCR was 41.9%, Groups A + C versus B + D (p = 0.231). 4-year disease-free survival (DFS) was significantly improved with X (p = 0.016) but not overall survival (p = 0.056). Triple -ve and HER2 +ve tumours, and persistent ALN disease were risk factors for metastases. X increased severe nail changes (p = 0.0002) and hand-foot syndrome (p = 0.014) without affecting QoL.ConclusionNAC-X did not increase breast and ALN pCR but improved 4-year DFS, without detriment to QoL.

Highlights

Neoadjuvant chemotherapy (NAC) is used to treat patients with large or locally advanced breast cancers (LLABCs), to downstage the disease and perform breast conserving surgery (Kaufmann et al 2012; Schott and Hayes 2012)
The groups were comparable in patient and tumour characteristics (79.5% T2, 85.7% ductal, 73.2% Oestrogen receptor (ER) +ve, 22.3% Human epidermal growth factor receptor 2 (HER2) +ve, 42% involved Axillary lymph node (ALN))
The aims of our study were to evaluate the effect of capecitabine in anthracycline-taxane NAC combinations, on pathological complete response (pCR) in the breast and ALNs, quality of life (QoL), disease-free survival (DFS) and overall survival (OS)

Summary

Introduction

Neoadjuvant chemotherapy (NAC) is used to treat patients with large or locally advanced breast cancers (LLABCs), to downstage the disease and perform breast conserving surgery (Kaufmann et al 2012; Schott and Hayes 2012). The addition of taxanes and trastuzumab to NAC combinations has improved the pathological complete response (pCR) in the breast and axillary lymph nodes (ALNs) (Kaufmann et al 2012; Smith et al 2002; Bear et al 2006; Semiglazov et al 2011). A pCR in the breast occurs in 17% to 30% of patients using various anthracycline-taxane combinations and histopathological criteria for assessing pCR (Smith et al 2002; Bear et al 2006; von Minckwitz et al 2010; Walker et al 2011). The use of trastuzumab with human epidermal growth factor receptor 2 positive (HER2 +ve) cancers has further increased the pCR responses (Kaufmann et al 2012; Semiglazov et al 2011)

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