Clinical Research Papers:
Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer
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Abstract
Carlo Palmieri1,2,3, Iain RJ Macpherson4, Kelvin Yan5, Felipe Ades6, Pippa Riddle5,7, Riz Ahmed5,7, Waheeda Owadally8, Barbara Stanley4, Deep Shah5, Ondrej Gojis5, Adam Januszewski5, Conrad Lewanski9, Rebecca Asher10, Daniel Lythgoe10, Evandro de Azambuja6, Mark Beresford8, Sacha J. Howell11
1Academic Department of Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK
2Liverpool and Merseyside Academic Breast Unit, The Linda McCartney Centre, Royal Liverpool University Hospital, Liverpool, UK
3The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Liverpool, UK
4Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK
5Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK
6Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
7Department of Clinical Oncology, West Middlesex University Hospital, London, UK
8Department of Clinical Oncology, The Royal United Hospital, Combe Park, Bath, UK
9Ealing Hospital NHS Trust, Middlesex, UK
10Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK
11University of Manchester, Institute of Cancer Sciences, Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
Correspondence to:
Carlo Palmieri, e-mail: [email protected]
Keywords: breast, neoadjuvant, trastuzumab, concomitant, sequential
Received: June 05, 2015 Accepted: July 05, 2015 Published: August 21, 2015
ABSTRACT
Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC.
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