Association of correlates of endogenous hormonal exposure with breast cancer risk in 426 families (United States) Dawn M. Grabrick 1 , Robert A. Vierkant 1 , Kristin E. Anderson 2 , James R. Cerhan 1 , V. Elving Anderson 2 & Thomas A. Sellers 1, * 1 Mayo Clinic, Department of Health Sciences Research, 200 First Street SW, Rochester, Minnesota 55905, USA; 2 University of Minnesota School of Public Health, Division of Epidemiology, Minneapolis, Minnesota, USA Received 8 June 2001; accepted in revised form 12 December 2001 Key words: breast neoplasms, epidemiology, pedigree, reproductive history, risk factors. Abstract Objective: Women with a strong family history of breast cancer are at significantly increased risk of developing the disease. There is emerging evidence that certain reproductive factors may further elevate risk in these women. We examined whether a family history of breast cancer modifies the association between correlates of endogenous hormonal exposures and breast cancer in a study of 426 families ascertained through breast cancer probands. Methods: Analyses of reproductive factors and breast cancer were performed on 395 sisters and daughters of probands, 3014 nieces and granddaughters, and 2768 marry-ins. Results: Through 226,266 person-years of follow-up since 1952, 240 women developed breast cancer. No statistically significant interactions were observed between relationship to proband and age at menarche, age at menopause, other characteristics of the menstrual cycle, parity, age at first and last birth, infertility, and total ovulatory years. Conclusions: Our findings suggest that most reproductive factors influence breast cancer risk similarly in women with and without a family history of breast cancer. Further studies are needed on individuals who are more homogeneous with regard to hereditary background. However, other options for prevention, such as prophylactic surgery or chemoprevention, may be necessary to have a substantial impact on risk reduction in women at high genetic risk. Introduction Women with a family history of breast cancer are at significantly increased risk of the disease [1]. Under- standing the modifying influence other factors may have on the risk of breast cancer in these women should ultimately lead to more focused prevention strategies. There is emerging evidence that certain reproductive factors may further elevate risk in these women. We recently reported a three-fold increased risk associated with use of early formulations of oral contraceptives [2]. At least two studies of BRCA1/2 carriers have reported an increased risk associated with parity [3, 4], in contrast to the protective effect seen in the general population [5]. Johannsson et al. [3] found significantly more women with BRCA1 mutations had their breast cancer diag- nosed during pregnancy or within 1 year of giving birth than cases who were non-carriers (OR ¼ 3.9, 95% CI: 1.4–10.8), but this study was limited by a small sample size. The study population in the report by Jernstrom et al. [4] included families of women ascertained through 14 different genetic counseling centers in North Amer- ica. After adjusting for ethnicity, the risk of breast cancer among parous carriers was approximately 80% greater than the risk of breast cancer among nulliparous carriers (95% CI: 1.2–2.8) [4]. These differences in risk compared with the general population underscore the need for additional studies to * Address correspondence to: Thomas A. Sellers, PhD, MPH, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Ph.: (507)284-5535; Fax: (507)266- 2478; Email: sellers.thomas@mayo.edu Cancer Causes and Control 13: 333–341, 2002. 333 Ó 2002 Kluwer Academic Publishers. Printed in the Netherlands.