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Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

2015; Impact Journals LLC; Volume: 7; Issue: 11 Linguagem: Inglês

10.18632/oncotarget.4801

1949-2553

Carlo Palmieri, Iain R. Macpherson, Kelvin Yan, Felipe Ades, Pippa Riddle, Riz Ahmed, Waheeda Owadally, Bárbara Stanley, Deep Shah, Ondřej Gojiš, Adam Januszewski, C. Lewanski, Rebecca Asher, Daniel Lythgoe, Evandro de Azambuja, Mark Beresford, Sacha J. Howell,

Peptidase Inhibition and Analysis

// Carlo Palmieri 1, 2, 3 , Iain RJ Macpherson 4 , Kelvin Yan 5 , Felipe Ades 6 , Pippa Riddle 5, 7 , Riz Ahmed 5, 7 , Waheeda Owadally 8 , Barbara Stanley 4 , Deep Shah 5 , Ondrej Gojis 5 , Adam Januszewski 5 , Conrad Lewanski 9 , Rebecca Asher 10 , Daniel Lythgoe 10 , Evandro de Azambuja 6 , Mark Beresford 8 , Sacha J. Howell 11 1 Academic Department of Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK 2 Liverpool and Merseyside Academic Breast Unit, The Linda McCartney Centre, Royal Liverpool University Hospital, Liverpool, UK 3 The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Liverpool, UK 4 Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK 5 Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK 6 Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium 7 Department of Clinical Oncology, West Middlesex University Hospital, London, UK 8 Department of Clinical Oncology, The Royal United Hospital, Combe Park, Bath, UK 9 Ealing Hospital NHS Trust, Middlesex, UK 10 Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK 11 University of Manchester, Institute of Cancer Sciences, Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK Correspondence to: Carlo Palmieri, e-mail: c.palmieri@liverpool.ac.uk 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.