|Grant Number:||5R01CA102740-03 Interpret this number|
|Primary Investigator:||Goodwin, Pamela|
|Organization:||Mt Sinai Hosp-Samuel Lunenfeld Res Inst|
|Project Title:||Prognosis in BRCA1 Associated Breast Cancer|
DESCRIPTION (provided by applicant): An international population-based, prospective cohort study, conducted in Northern California, Australia and Ontario (Canada), will build upon activities of the Cooperative Familial Registry for Breast Cancer Studies (CFRBCS) to study women with BRCA1 associated or sporadic breast cancer to address the following objectives: (1) To examine the germline mutations in BRCA1 on risk of distant recurrence and death in women with newly diagnosed locoregional breast cancer (examination of the impact of mutations on distant recurrence is our primary objective). (2) To explore the frequency and prognostic importance of traditional pathologic factors and selected molecular markers (p53, HER2/neu) on distant recurrence and death in BRCA1 mutation carriers. (3) To describe the associations of treatment (systemic therapy, surgery, radiation) with outcomes (local breast events, contralateral breast events, distant recurrence, death) for BRCA1 mutation carriers and sporadic cases in order to generate hypotheses regarding treatment effects that can be tested in future randomized trials. Specifically, we will review medical records to collect detailed clinical, treatment and outcome information on women enrolled onto the prognostic study and we will perform a series of immunohistochemical assays for hormone receptors, p53 and HER2/neu. Additional information will be drawn from previously funded CFRBCS activities including detailed pathology review, results of mutation analysis, family history and demographic data. Data from these 2 sources will be incorporated into the statistical analysis which will address our 3 study objectives. Our proposed research improves upon existing research because it is population-based, prospective, involves rigorous control of clinical and pathologic prognostic factors, and includes sufficient subjects with BRCA1 associated hereditary breast cancer (100-140 women) that objectives can be addressed with adequate power (>80% power to detect hazard ratios under 2.0). It will also lead to the establishment of a well characterized cohort of 3000 women with standard clinical and pathologic data that can be used as a resource for future research into prognostic effects of mutations in BRCA2 (once testing is complete) and in other yet to be discovered breast cancer predisposition genes. Because this research is nested within the CFRBCS, the objectives can be addressed in a timely and cost effective manner.
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