The Association Between Body Mass Index and Immunohistochemical Subtypes in Breast Cancer

Abstract

Background:Body mass index (BMI) is defined as a poor prognostic factor in patients with breast cancer(BC). However, there are controversial results regarding the various effects of BMI on BC, hence the exactpathophysiology of the relation between obesity and BC is still under debate, and remains unclear. Thispaper aims to investigate the association between BMI at presentation and BC subtypes defined accordingto the immunohistochemical classification in both premenopausal and postmenopausal patients with BC.Patients and methods:This study is a retrospective and explorative analysis of the 3767 female BC pa-tients from a single center. All patients' BMI at the time of initial diagnosis and tumor demographics wererecorded. BMI was stratified into 3 groups as normal-weighted (BMI<25 kg/m2), over-weighted(BMI¼25e29.9 kg/m2), and obese (BMI 30 kg/m2). Immunohistochemical classification of thetumors was categorized into 4 groups as follows; luminal-like, HER2/luminal-like, HER2-like, and triple-negative according to the ER/PR and HER2 status. Distribution of Immunohistochemical subtypes, tumorcharacteristics, and overall survival (OS) analysis were evaluated according to the BMI groups in bothpremenopausal and postmenopausal patients.Results:Median BMI of premenopausal and postmenopausal patients was 25.5 (kg/m2) and 28.8 (kg/m2),respectively (P<0.001). In parallel with the increasing age, patients were more obese at diagnosis inboth premenopausal (P<0.001) and postmenopausal period (P<0.001). Triple-negative subtype wassignificantly more frequent in premenopausal patients with BMI 30 kg/m2compared to BMI<30 kg/m2(P¼0.007). Additionally, premenopausal patients with BMI 30 kg/m2had less common luminal-likesubtype (P¼0.033) and more frequently presented with higher tumor stage (P¼0.012) and tumorgrade (P¼0.004) compared to patients with BMI<25 kg/m2. On the other hand, premenopausal patientswith BMI<25 kg/m2had significantly more ER-positive tumors (P<0.001) and lower stages of disease(P¼0.01) compared to their counterparts with BMI 25 kg/m2. Premenopausal obese patients withtriple-negative (P¼0.001) and luminal-like subtype (P¼0.002) had significantly shorter OS durationcompared to overweight counterparts. HER2/luminal-like subtype was found to be significantly greaterin postmenopausal overweight patients (P¼0.005). However, BMI had no any other significant effect onsurvival and immunohistochemical subtypes in postmenopausal patients. Multivariate analysis revealedthat triple-negative subtype, grade III tumor, BMI 30 kg/m2,T3e4(P<0.001), nodal involvement,metastatic disease, and lymphovascular involvement were significantly associated with poorer OS.Conclusion:Our data indicated that BMI was an independent factor in patients with BC, with an asso-ciation indicating a decreased incidence for luminal-like subtype and increased incidence for triple-negative subtype among premenopausal patients. However, this significance was not found inpostmenopausal patients. Accordingly, a plausible etiological heterogeneity in BC might play a roleamong immunohistochemical subtypes in every life stage of women