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

Disclosures

Breast Cancer Res. 2020;22(115) 

In This Article

Abstract and Introduction

Abstract

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/m2), normal (≥ 18.5; < 25 kg/m2), overweight (≥ 25; < 30 kg/m2), and obese (≥ 30 kg/m2) 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.

Introduction

Obesity is one of the most common public health problems worldwide, and its incidence is increasing steadily over the past two decades in both developed and developing countries. Epidemiological data confirm that obesity is independently associated with an increased incidence of various solid tumors, including breast cancer (BC), and is a poor prognostic factor in early and metastatic BC patients.[1,2]

Despite its impact on BC development and prognosis, few studies have investigated the predictive value of obesity for response to systemic therapies mostly focusing on unselected BC patient populations.[3] Hence, it is not surprising that the association between obesity and treatment response is still controversial.

In HER2-positive early BC patients, no significant difference was reported between obese and non-obese patients treated in the N9831 adjuvant trial, which compared anthracycline/taxane-based regimen versus its combination with trastuzumab, as the trend toward decreased disease-free survival observed in obese patients treated with chemotherapy alone was reverted by combining chemotherapy with trastuzumab.[4] In the neo-adjuvant setting, the relationship between obesity and response to anti-HER2 agents has been evaluated mainly by retrospective or institutional series, which reported that obesity can independently and negatively affect response rate, including pathological complete response (pCR).[5–7]

Here, we sought to analyze if the relationship between obesity and adverse clinical and pathological characteristics, primary treatment response, and disease outcome in HER2-positive early BC patients treated in the setting of a large prospective randomized clinical trial such as NeoALTTO.[8]

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