Abstract 714: Weight changes between one year before and following breast cancer diagnosis in relation to mTOR protein expression in tumor tissues in the Women’s Circle of Health Study

Abstract

Abstract Background: Obesity is an important prognostic factor for breast cancer. Aberrant activation of the mechanistic Target of Rapamycin (mTOR) pathway is associated with obesity, cross-sectionally, as well as with breast cancer survival. This study aimed to examine the association of weight change between one year before and following cancer diagnosis with a panel of mTOR protein markers in breast tumors. The study hypothesis was that greater weight gain compared to less or no weight gain would be associated with higher mTOR protein expression in breast tumors. Methods: Study participants were 698 newly-diagnosed breast cancer cases (545 Black women and 153 White women) from the Women’s Circle of Health Study (WCHS). Surgical tissue microarrays were stained for mTOR, phosphorylated mTOR, phosphorylated AKT, and phosphorylated P70S6K using immunohistochemistry. In-home interviews were conducted approximately 10 months after breast cancer diagnosis, and anthropometric measurement was taken by trained staff. Participants reported body weight one year before the diagnosis, excluding the time of pregnancy or nursing. Linear regression analyses were conducted to estimate percent differences in protein expression across quartiles of weight change, adjusting for age, race, BMI one year before diagnosis, menopausal status, history of diabetes, and molecular tumor subtype. Results: Study participants had a mean age of 52.7 (SD = 10.8) years and BMI one year before diagnosis of 30.7 (SD = 6.9) kg/m2. The proportions of participants who had loss ≥5 lbs, loss <5 lbs, no change to gain <5 lbs, and gain ≥5 lbs in weight were 33.7%, 16.2%, 16.2%, and 33.7%, respectively. The fourth vs. first quartile of the weight change was associated with a higher protein expression of mTOR (35.3%, 95% CI = 3.8%, 76.5%), and there was a dose-response pattern (P-trend = 0.0273). No associations were observed between weight change and phosphorylated protein expression. Conclusion: Short-term weight gain before breast cancer diagnosis and following diagnosis may play a role in breast tumor mTOR protein expression. Our findings warrant validation in a study with a prospective measurement of weight gain before breast cancer surgery. Citation Format: Mmadili N. Ilozumba, Angela R. Omilian, Song Yao, Weizhou Zhang, Susmita Datta, Warren Davis, Chi-Chen Hong, Elisa V. Bandera, Thaer Khoury, Christine B. Ambrosone, Ting-Yuan David Cheng. Weight changes between one year before and following breast cancer diagnosis in relation to mTOR protein expression in tumor tissues in the Women’s Circle of Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 714.