Kantonsspital St.Gallen

Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial

Serena Di Cosimo, Luca Porcu, Dominique Agbor-Tarh, Saverio Cinieri, Maria Alice Franzoi, Maria Carmen De Santis, Cristina Saura, Jens Huober, Debora Fumagalli, Miguel Izquierdo, Martine Piccart, Maria Grazia Daidone & Evandro De Azambuja


Obesity is a risk factor for breast cancer (BC) development, recurrence, and death. In view of this, we aimed to investigate the clinical value of obesity in BC patients treated with anti-HER2 therapies in the NeoALTTO trial, which randomized 455 patients to neo-adjuvant lapatinib, trastuzumab, or their combination plus paclitaxel.

Patients were classified according to their basal body mass index (BMI) into underweight (< 18.5 kg/m), normal (≥ 18.5; < 25 kg/m), overweight (≥ 25; < 30 kg/m), and obese (≥ 30 kg/m) WHO categories. Univariate and multivariate logistic regression analyses were performed using BMI as a categorical variable. Pathological complete response (pCR) and event-free survival (EFS) were the NeoALTTO primary and secondary outcomes, respectively.

Among 454 patients analyzed, 14 (3%), 220 (48%), 137 (30%), and 83 (18%) were classified as underweight, normal weight, overweight, and obese, respectively; 231 (51%) and 223 (49%) had hormone receptor (HR)-positive and HR-negative primary tumors; 160 (35%) achieved pCR. In the overall patient population, no association was found between BMI groups and pCR, as we reported pCR rates of 57.1%, 35%, 30.7%, and 39.8% in underweight, normal weight, overweight, and obese cases, respectively. In contrast, in HR-positive tumors, overweight or obesity was generally associated with decreased likelihood of achieving a pCR independently of other clinical variables, including planned surgery, nodal status, and tumor size (odds ratio [OR] = 0.55, 95%CI 0.30-1.01, as compared to normal or underweight; p = 0.053); notably, no differential effect of BMI with respect to pCR was observed in HR-negative cases (odds ratio [OR] = 1.30, 95%CI 0.76-2.23, as compared to normal or underweight; p = 0.331), resulting in a statistically significant interaction between BMI and HR status (p = 0.036). There was no association between BMI and EFS neither in the overall nor in the HR-positive population, but this analysis was under-powered.

NeoALTTO patients overweight or obese at baseline and with HR-positive primary BC appeared less likely to achieve pCR after neo-adjuvant anti-HER2 therapies. This finding paves the way to future research in targeting the interplay between HER2/HR signaling and metabolism.
citation Di Cosimo S, Porcu L, Agbor-Tarh D, Cinieri S, Franzoi M A, De Santis M C, Saura C, Huober J, Fumagalli D, Izquierdo M, Piccart M, Daidone M G, de Azambuja E. Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial. Breast Cancer Res 2020; 22:115.
type journal paper/review (English)
date of publishing 27-10-2020
journal title Breast Cancer Res (22/1)
ISSN electronic 1465-542X
pages 115
PubMed 33109233
DOI 10.1186/s13058-020-01356-w