Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer.
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.
Academic Department of Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK.|Liverpool and Merseyside Academic Breast Unit, The Linda McCartney Centre, Royal Liverpool University Hospital, Liverpool, UK.|The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Liverpool, UK.
Carlo
C
Palmieri
Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK.
Iain Rj
IR
Macpherson
Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK.
Kelvin
K
Yan
Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Felipe
F
Ades
Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK.|Department of Clinical Oncology, West Middlesex University Hospital, London, UK.
Pippa
P
Riddle
Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK.|Department of Clinical Oncology, West Middlesex University Hospital, London, UK.
Riz
R
Ahmed
Department of Clinical Oncology, The Royal United Hospital, Combe Park, Bath, UK.
Waheeda
W
Owadally
Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK.
Barbara
B
Stanley
Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK.
Deep
D
Shah
Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK.
Ondrej
O
Gojis
Department of Medical Oncology, Imperial College Healthcare NHS Trust, London, UK.
Adam
A
Januszewski
Ealing Hospital NHS Trust, Middlesex, UK.
Conrad
C
Lewanski
Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
Rebecca
R
Asher
Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, UK.
Daniel
D
Lythgoe
Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Evandro
E
de Azambuja
Department of Clinical Oncology, The Royal United Hospital, Combe Park, Bath, UK.
Mark
M
Beresford
University of Manchester, Institute of Cancer Sciences, Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
Sacha J
SJ
Howell
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D000068878:Trastuzumab / Q000008:administration & dosage*; D016896:Treatment Outcome
D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
breast; concomitant; neoadjuvant; sequential; trastuzumab