1. ¹Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA
2. ²Department of Nutrition Research, University of Oslo, Oslo, Norway
3. ³Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
4. ⁴Division of Public Health, Fred Hutchinson Cancer Research Center and Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA
5. ⁵Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA
6. ⁶Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
7. ⁷Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
8. ⁸Department of Internal Medicine, Karmanos Cancer Institute at Wayne State University, Detroit, MI, USA
9. ⁹Department of Obstetrics and Gynecology, Baystate Medical Center, Springfield, MA, USA
10. ¹⁰Cancer Centers Branch, National Cancer Institute, Bethesda, MD, USA
11. ¹¹Contraception and Reproductive Health Branch, Center for Population Research, National Institute of Child Health and Human Development, NIH, DHHS, Bethesda, MD, USA

Correspondence: Dr G Ursin, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Los Angeles, CA 90089, USA. E-mail: gursin@usc.edu

Received 6 January 2005; Revised 13 June 2005; Accepted 20 June 2005; Published online 2 August 2005.

Abstract

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case–control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.