title: Women with large (≥3 cm) 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.
abstract: OBJECTIVE
  To 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).
  
  
  METHODS
  117 women were enrolled, 112 randomised to 2 cycles of AC (60 mg/m(2), 600 mg/m(2)) 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/m(2)) (Group A) or T (75 mg/m(2)) and X (2000 mg/m(2)/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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  NAC-X did not increase breast and ALN pCR but improved 4-year DFS, without detriment to QoL.
authors.affiliation: Research & Development Department, Lincoln County Hospital, Greetwell Road, Lincoln, LN2 5QY UK ; Lincoln Breast Unit, Lincoln County Hospital, Greetwell Road, Lincoln, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eremin
authors.affiliation: Department of Pathology, PathLinks, Lincoln County Hospital, Greetwell Road, Lincoln, UK.
authors.forename: Ged
authors.initials: G
authors.lastname: Cowley
authors.affiliation: Medical Research Centre, University of Hull, Hull, UK.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Walker
authors.affiliation: Lincoln Breast Unit, Lincoln County Hospital, Greetwell Road, Lincoln, UK ; Department of Oncology, Lincoln County Hospital, Greetwell Road, Lincoln, UK.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Murray
authors.affiliation: Department of Radiology, Lincoln County Hospital, Greetwell Road, Lincoln, UK.
authors.forename: Monika
authors.initials: M
authors.lastname: Stovickova
authors.affiliation: Research & Development Department, Lincoln County Hospital, Greetwell Road, Lincoln, LN2 5QY UK ; Lincoln Breast Unit, Lincoln County Hospital, Greetwell Road, Lincoln, UK ; Division of Surgery, The University of Nottingham, Queen's Medical Centre, Derby Road, Nottingham, UK.
authors.forename: Oleg
authors.initials: O
authors.lastname: Eremin
keywords: Breast cancer; Neoadjuvant chemotherapy; Response; Survival