Abstract P4-15-05: Effects on outcome of concomitant neoadjuvant chemotherapy-trastuzumab compared with sequential neoadjuvant chemotherapy followed by post-operative trastuzumab
Authors: Palmieri Carlo , Macpherson Iain RJ , Yan Kelvin , Ades Moraes Felipe , Riddle Pippa , Ahmed Riz , Owadally Waheeda , Stanley Barabara , Shah Deep , Gojis Ondrej , Januszewski Adam , Lewanski Conrad , Asher Rebecca , Lythgoe Daniel , De Azambuja Evandro , Beresford Mark , Howell Sacha J 
Published: May 2015

Abstract
Background:
Neoadjuvant chemotherapy delivered with trastuzumab (NCT) has been shown to increase the rates of pathological complete response (pCR) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting has been associated with improved event free survival (EFS). However, no study has yet investigated the effect on outcomes of NCT compared to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT). This study sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early breast cancer.
Methods:
Women with HER2 positive invasive breast cancers treated with neoadjuvant chemotherapy between 2006-2010 were identified at each of 7 European institutions and the case notes reviewed. Preoperative clinical, radiological and pathological details, treatment details and pathology results following breast surgery were reviewed. To be defined as NCT at least one dose of trastuzumab needed to be given preoperatively. pCR was defined as absence of invasive disease in breast and lymph nodes. Multivariable Cox regression and logistic regression were used to Survival outcomes for event-free survival (EFS) were calculated by log rank analysis model the influence of a number of factors on event-free survival (EFS) and pCR respectively.
Results:
236 patients were identified; 138 (58%) received NCAT & 98 (42%) received NCT. The median follow up for the whole group was 53.7 months (IQR 41.7-68.8), 61.5 months (IQR 50.3-78.5) for NCAT group and 44.8 months (range 37-53.9) for NCT group. The 5-year EFS for NCAT vs NCT was 59.3% (95% CI: 49.8-67.6) and 69.6% (95% CI: 51.5-82.0) respectively. The unadjusted hazard ratio (HR) for EFS with NCT compared with the NCAT was 0.63 (95% CI 0.37–1.08; p=0.091). NCT significantly increased the odds of having pCR relative to NC (OR: 4.39 (2.18-8.86); p&lt;0.001), and pCR was associated with a significantly improved EFS, with an unadjusted HR of 0.23 (95% CI 0.08–0.64; p=0.002). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS. NCT was associated with a reduced risk of relapse relative to NCAT (HR 0.48, 95% CI 0.26-0.89). In ER negative tumours NCT was significantly associated with a reduced risk of an event relative to NCAT (HR:0.25; 95% CI, 0.10-0.62), this was not observed for ER positive tumours (HR: 1.07; 95% CI, 0.46-2.52).
Conclusion
Concomitant as compared to sequential trastuzumab is associated with improved outcomes in the neoadjvuant setting for women with ER negative tumours. These data further support the need for the early introduction of targeted combination therapy in women with ER negative/HER2 positive BC.
Citation Format: Carlo Palmieri, Iain RJ Macpherson, Kelvin Yan, Felipe Ades Moraes, Pippa Riddle, Riz Ahmed, Waheeda Owadally, Barabara Stanley, Deep Shah, Ondrej Gojis, Adam Januszewski, Conrad Lewanski, Rebecca Asher, Daniel Lythgoe, Evandro De Azambuja, Mark Beresford, Sacha J Howell. Effects on outcome of concomitant neoadjuvant chemotherapy-trastuzumab compared with sequential neoadjuvant chemotherapy followed by post-operative trastuzumab [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-05.