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01-12-2021 | Obesity | Research article

Body fatness and breast cancer risk in relation to phosphorylated mTOR expression in a sample of predominately Black women

Authors: Ting-Yuan David Cheng, Angela R. Omilian, Song Yao, Weizhou Zhang, Susmita Datta, Wiam Bshara, Rochelle Payne Ondracek, Warren Davis, Song Liu, Chi-Chen Hong, Elisa V. Bandera, Thaer Khoury, Christine B. Ambrosone

Published in: Breast Cancer Research | Issue 1/2021

Abstract

Background

The mechanistic target of rapamycin (mTOR) pathway promoted by positive energy imbalance and insulin-like growth factors can be a mechanism by which obesity influences breast cancer risk. We evaluated the associations of body fatness with the risk of breast cancer varied with phosphorylated (p)-mTOR protein expression, an indication of the pathway activation.

Methods

Women with newly diagnosed breast cancer (n = 715; 574 [80%] Black and 141 [20%] White) and non-cancer controls (n = 1983; 1280 [64%] Black and 713 [36%] White) were selected from the Women’s Circle of Health Study. Surgical tumor samples among the cases were immunostained for p-mTOR (Ser2448) and classified as p-mTOR-overexpressed, if the expression level ≥ 75th percentile, or p-mTOR-negative/low otherwise. Anthropometrics were measured by trained staff, and body composition was determined by bioelectrical impedance analysis. Odds ratios (ORs) of p-mTOR-overexpressed tumors and p-mTOR-negative/low tumors compared to controls were estimated using polytomous logistic regression. The differences in the associations by the p-mTOR expression status were assessed by tests for heterogeneity.

Results

Cases with p-mTOR-overexpressed tumors, but not cases with p-mTOR-negative/low tumors, compared to controls were more likely to have higher body mass index (BMI), percent body fat, and fat mass index (P-heterogeneity < 0.05), although the OR estimates were not significant. For the measurement of central adiposity, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 2.52, 95% CI = 1.46 to 4.34) and Q4 (OR = 1.99, 95% CI = 1.12 to 3.50) of waist circumference (WC) compared to controls. Similarly, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 1.82, 95% CI = 1.11 to 2.98) and Q4 (OR = 1.81, 95% CI = 1.11 to 2.98) of WHR compared to controls. These associations of WC and waist-to-hip ratio (WHR) did not differ by tumor p-mTOR status (P-heterogeneity = 0.27 and 0.48, respectively).

Conclusions

Our findings suggest that in this population composed of predominately Black women, body fatness is associated with breast cancer differently for p-mTOR overexpression and p-mTOR negative/low expression. Whether mTOR plays a role in the obesity and breast cancer association warrants confirmation by prospective studies.

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Title: Body fatness and breast cancer risk in relation to phosphorylated mTOR expression in a sample of predominately Black women
Authors: Ting-Yuan David Cheng
Angela R. Omilian
Song Yao
Weizhou Zhang
Susmita Datta
Wiam Bshara
Rochelle Payne Ondracek
Warren Davis
Song Liu
Chi-Chen Hong
Elisa V. Bandera
Thaer Khoury
Christine B. Ambrosone
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Obesity
Obesity
Breast Cancer
Breast Cancer
Published in: Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-021-01458-z

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