Project Summary/Abstract Approximately 82% of US women have ever used oral contraceptives (OCs) during their reproductive lives and there is a modest increased risk of breast cancer associated with recent use of OCs among young women, yet there have been few studies that have assessed the magnitude of this risk according to OC formulation or breast cancer subtype. There have been important changes in OC formulations over time including a reduction in estrogen dose and the inclusion of new synthetic progestins. Given the varying estrogenic, progestational, and androgenic activities of different synthetic progestins, it is important to investigate which specific types of OCs are related to breast cancer risk. It is also important to assess whether OC use is associated with risk of particular breast cancer subtypes. In response to the National Institutes of Health announcement for small grants in cancer epidemiology, we propose a pilot study assessing whether the effect of current and recent OC use on breast cancer risk varies by OC formulation or by breast cancer subtype within Group Health Cooperative (GHC), a large managed health care system in western Washington State. Group Health is part of a research network of 14 health maintenance organizations called the Cancer Research Network (CRN). This pilot study will provide vital preliminary data for a potential multisite study within the CRN that would pool electronic OC pharmacy data from numerous sites and link these exposure data to cancer endpoints. Considering the large differences in prognosis according to breast cancer subtype, frequency of OC use, recent OC formulation changes, and the limited data thus far assessing specific OC formulations defined by pharmacy data, this study is of great public health importance. This nested case-control study will include GHC women who are 20-49 years of age between 1996 and 2008 and have been enrolled continuously at GHC for at least one year immediately before diagnosis date (or a comparable date for controls). Cases will be diagnosed with a primary breast cancer within the study time period and controls will be frequency-matched to cases by age at diagnosis, calendar year, and years of enrollment at GHC. OC exposure information will be obtained via electronic pharmacy records. Breast cancer risk factor information will be ascertained from existing electronic questionnaire data and via medical record review for women without questionnaire data. The specific aims of this study are: (1) To determine if current and recent use of various OC formulations (grouped by type, dose, and potency of estrogen and progestin) are associated with breast cancer risk among women 20-49 years of age. (2) To determine if the relationships between current and recent OC use and breast cancer risk vary by histologic type or by expression of estrogen receptor, progesterone receptor, and HER2-neu (considered both individually and jointly). PUBLIC HEALTH RELEVANCE: Project Narrative Evidence supports a modest increased risk of breast cancer among young women associated with recent use of oral contraceptives (OCs);however there are limited data assessing this risk by specific OC formulation (particularly newer formulations) or by breast cancer subtype. This study will use automated pharmacy dispensing data in a large managed health care setting to accurately categorize OC exposure according to formulation and examine overall breast cancer risk and risk according to histology and expression of different tumor markers. This area of research is critical given the high frequency of OC use, heterogeneity of OC formulations, changes in OC formulations over time, and the morbidity and mortality associated with different breast cancer subtypes.