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
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
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.
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