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Relationship between Established Breast Cancer Risk Factors and Risk of Seven Different Histologic Types of Invasive Breast Cancer

¹ Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, Washington; ² Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California; ³ Division of Reproductive Health, Centers for Disease Control and Prevention; ⁴ Rollins School of Public Health, Emory University, Atlanta, Georgia; ⁵ Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; ⁶ Division of Hematology and Oncology, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; ⁷ Department of Nutrition, University of Oslo, Oslo, Norway; ⁸ Department of Obstetrics and Gynecology, Baystate Medical Center, Springfield, Massachusetts; and ⁹ Contraception and Reproductive Branch, Center for Population Research, National Institute of Child Health and Human Development, NIH, Department of Health and Human Services, Bethesda, Maryland

Requests for reprints: Christopher I. Li, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-C308, P.O. Box 19024, Seattle, WA 98109-1024. Phone: 206-667-7444; E-mail: cili{at}fhcrc.org

Background: Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types.

Methods: Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression.

Results: Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma.

Conclusions: Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer. (Cancer Epidemiol Biomarkers Prev 2006;15(5):946–54)

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