Journal Article

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

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

2020

Overview

Background 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. Methods Patients were classified according to their basal body mass index (BMI) into underweight (< 18.5 kg/m 2 ), normal (≥ 18.5; < 25 kg/m 2 ), overweight (≥ 25; < 30 kg/m 2 ), and obese (≥ 30 kg/m 2 ) 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. Results 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. Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adjuvant chemotherapy / Adjuvant therapy / Analysis / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomedical and Life Sciences / Biomedicine / Body Mass Index / Body weight / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Clinical trials / ErbB-2 protein / Estrogen Receptor alpha - antagonists & inhibitors / Estrogen Receptor alpha - metabolism / Female / Health aspects / HER2-positive breast cancer / Humans / Insulin resistance / Lapatinib / Lapatinib - administration & dosage / Medical prognosis / Middle Aged / Monoclonal antibodies / Neo-adjuvant treatment / Neoadjuvant Therapy - methods / Obesity / Obesity - physiopathology / Oncology / Overweight / Overweight - physiopathology / Paclitaxel / Paclitaxel - administration & dosage / Pathological complete response / Patients / Receptor, ErbB-2 - antagonists & inhibitors / Receptor, ErbB-2 - metabolism / Risk Factors / Short Report / Statistical analysis / Surgery / Surgical Oncology / Survival Rate / Targeted cancer therapy / Trastuzumab / Trastuzumab - administration & dosage / Treatment Outcome / Tumors / Underweight / Variables