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

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  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.

Clinical trial identification

NCT00553358

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale dei Tumori

Funding

None

Disclosure

I. Bradbury: Ian Bradbury's institution has received funding from GlaxoSmithKline and Roche.

J. Baselga: Honoraria received from Roche.

S. Sarp: Novartis AG.

M. Piccart: Honoraria received from GlaxoSmithKline and Roche, research funding to Institution from GlaxoSmithKline.

E. de Azambuja: Advisory board and travelling grant from GlaxoSmithKline, speaker for Roche.

S. Di Cosimo: Speaker for GlaxoSmithKline.

All other authors have declared no conflicts of interest.