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Breast Cancer Risk and Hormone Receptor Status in Older Women by Parity, Age of First Birth, and Breastfeeding: A Case-Control Study

¹ National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia; ² Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California; ³ Beckman Research Institute, City of Hope National Medical Center, Duarte, California; ⁴ Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute; ⁵ Contraceptive and Reproductive Health Branch, Center for Population Research, National Institute of Child Health and Development, Bethesda, Maryland; ⁶ Division of Public Health Sciences, Fred Hutchinson Cancer Research Centre; ⁷ Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington; ⁸ Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia; ⁹ Division of Hematology and Oncology, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; ¹⁰ Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania; ¹¹ Department of Obstetrics and Gynecology, Tufts University School of Medicine, Baystate Medical Center, Springfield, Massachusetts; and ¹² Institute of Basic Medical Sciences, Department of Nutrition, University of Oslo, Oslo, Norway

Requests for reprints: Giske Ursin, Department of Preventive Medicine, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Room 4407, 1441 Eastlake Avenue, Los Angeles, CA 90089. Phone: 323-865-0423; Fax: 323-865-0142. E-mail: gursin{at}usc.edu

Background: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)–positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers.

Methods: We used multivariable logistic regression analysis to investigate whether age at first birth (<25 or 25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages 55 years who participated in the Women's Contraceptive and Reproductive Experiences Study.

Results: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (P_{heterogeneity} = 0.0007). This protective effect was restricted to ERPR-positive breast cancer (P_{heterogeneity} = 0.004). Late age at first birth increased the risk of ERPR-negative cancers.

Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (P_trend = 0.0001) and among women who breastfed (P_trend = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer.

Conclusions: These findings suggest that the effect of parity on a woman's long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1723–30)