Effect of body mass index (BMI) on response to neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC): Analysis from NeoALLTO trial

Abstract

Background: Obesity is a risk factor for the development of BC in postmenopausal women and has been linked to increased risk of recurrence and death in BC patients ( pts). Herein, we aimed to investigate the prognostic and predictive role of obesity in HER2 positive BC pts treated with neoadjuvant anti-HER2 therapies. Methods: NeoALTTO enrolled 455 women with invasive HER2 positive BC and compared rates of pathologic complete response (pCR) to neoadjuvant lapatinib, trastuzumab or their combination given alone for 6 weeks and then combined with weekly paclitaxel. In the present analysis, pts' outcomes in terms of event free survival (EFS), overall survival (OS) and pCR rates were evaluated according to hormone receptor (HR) status and BMI. We used the World Health Organisation (WHO) classification for BMI categories. Results: 14 pts (3.1%) were underweight (BMI <18.5 kg/m2), 220 (48.5%) had a normal BMI (18.5-25.0 kg/m2), 137 (30.2%) were overweight (BMI 25.0-30.0 kg/m2) and 83 (18.3%) were classifiable as obese (BMI > 30.0 kg/m2). The impact of BMI on pCR rate was studied by collapsing BMI into two groups, above and below 25 kg/m2. There were no apparent effects of BMI when an effect independent of HR status was fitted [odds ratio (OR) for effect of normal BMI relative to high 1.12, 95% confidence interval (CI) 0.72-1.79]. However, there was a significant interaction between BMI and HR status (p 0.036). In the interaction model, a modest effect of BMI was seen in HR positive pts (OR 2.02, 95% CI 1.04-3.92), whereas in HR negative pts there were no apparent effects (OR 0.79, 95% CI 0.45-1.39). BMI did not predict either EFS or OS in any treatment arms or HR subgroups, but NeoALLTO was not powered for these endpoints. Conclusions: The present study found no significant impact of BMI in response to neoadjuvant therapy in the whole HER2 positive population. However, a significant correlation was seen in pts with HR positive tumours. Our data potentially pave the way to future research in developing combined therapeutic strategies for HER2 positive luminal BC, with the intent of obtaining a complete blockade of the driving growth factor signals via both HER2 and HRs.