Association of oral contraceptives with breast cancer risk in a population-based sample of 426 breast cancer families. D.M. Grabrick, J.R. Cerhan, F.J. Couch, R.A. Vierkant, T.M. Therneau, C.M. Vachon, J.E. Olson, V.S. Pankratz, L.C. Hartmann, T.A. Sellers. Mayo Clinic, Rochester, MN.

   Oral contraceptives (OCs) are weakly associated with an increased risk of breast cancer (BC) in the general population, but some data suggest a higher risk among BRCA1 and BRCA2 mutation carriers. This is clinically important as women in breast-ovarian cancer families may consider OC use to reduce their ovarian cancer risk. We analyzed data from the Minnesota Breast Cancer Family Study, a historical cohort study of relatives of 426 BC cases identified between 1944 and 1952, and followed through 1996. Ninety-eight percent of eligible families were recruited, and 93% of members participated. OC use and cancer incidence in sisters, daughters, granddaughters, nieces, and marry-ins were determined through telephone interviews. Through 1996, a total of 239 incident BCs were identified in the cohort of 6,150 women at risk. The lifetime prevalence of ever having used OCs was 51% overall and was similar for blood relatives and marry-ins (p=0.99). We used proportional hazards regression, accounting for birth cohort and correlated family data, to model the association between a time-dependent definition of OC use and age at onset of BC. The association of OC use with BC was examined within strata defined by degree of relationship to the proband, with never users as the reference category within each stratum. Among sisters and daughters, women who used OCs for 1 to 4 years were at 4.2-fold greater risk (95% C.I.: 2.1-8.6); for duration of use greater than 4 years the risk estimate was 2.2 (95% C.I.: 0.8-6.4). The corresponding risk estimates for granddaughters and nieces were 1.3 and 1.2, and for marry-ins 1.1 and 1.3, all nonsignificant. When analyses were repeated among the subset of families with 3+ breast or ovarian cancers, risks associated with OC use were further elevated among first-degree relatives: 5.5 (2.4-12.5) and 3.3 (1.0-11.0) for 1 to 4 and greater than 4 years, respectively. These data suggest that use of oral contraceptives may significantly increase risk of breast cancer among women with a family history of breast cancer, especially those with a strong family history.