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Cancer Control Research

Abstract

DESCRIPTION (Applicant's Description) An increasing number of reports substantiate that obesity is a risk factor for recurrence and mortality in breast cancer patients. Heavier women have an increased risk of recurrence or death, compared to thinner women, even after controlling for other prognostic factors. We hypothesize that women of greater body mass present with larger tumors (and ultimately a worse prognosis) due to the following endocrine- metabolizing hormones that are associated with obesity and that may mediate rapid breast tumor proliferation: leptin, type 1 insulin-like growth factor (IGF-1), insulin-like growth factor binding protein type 3 (IGFBP-3) and insulin. IGF-1, IGFBP-3 and insulin have all been associated with both increased breast cancer incidence and decreased survival from the disease. These hormones are associated with obesity either directly or through mediating pathways (e.g., growth hormone/IGF axis). Leptin levels are highly correlated with fat mass. Recently, two epidemiologic studies found a relationship between circulating leptin levels and breast cancer incidence. A population-based cohort of invasive breast cancer cases first identified through two large studies of breast cancer etiology in young women and now being followed for factors that affect survival serves as the underlying infrastructure for this project. Extensive information on participants has been collected, using detailed questionnaires, an extensive medical records review, as well as a histopathology review and molecular analysis of tumors. Plasma samples were collected from participants in the original studies and will be used to complete assays of the hormones of interest. For the proposed pilot study, a comparison will be made of hormone levels across groups defined by tumor size and body mass index (BMI) among young invasive breast cancer cases. Hormone levels will also be examined for their relationship with tumor prognostic markers. There is a critical need to elucidate possible biologic mechanisms underlying the poor prognosis associated with obesity in breast cancer patients. Findings from this study could begin to clarify a mechanism by which adiposity affects prognosis from breast cancer.