This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cerhan, J. R. Articles by Vachon, C. M. Search for Related Content PubMed PubMed Citation Articles by Cerhan, J. R. Articles by Vachon, C. M.

Prenatal and Perinatal Correlates of Adult Mammographic Breast Density

Departments of ¹ Health Sciences Research and ² Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota and ³ Division of Cancer Prevention and Control, H. Lee Moffitt Cancer and Research Institute, Tampa, Florida

Requests for reprints: James R. Cerhan, Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-538-0499; Fax: 507-266-2478. E-mail: cerhan.james{at}mayo.edu

Background: Adult mammographic percent density is one of the strongest known risk factors for breast cancer. In utero exposure to high levels of endogenous estrogens (or other pregnancy hormones) has been hypothesized to increase breast cancer risk in later life. We examined the hypothesis that those factors associated with higher levels of estrogen during pregnancy or shortly after birth are associated with higher mammographic breast density in adulthood.

Methods: We analyzed data on 1,893 women from 360 families in the Minnesota Breast Cancer Family Study who had screening mammograms, risk factor data, over age 40, and no history of breast cancer. Prenatal and perinatal risk factor data were ascertained using a mailed questionnaire. Mammographic percent density and dense area were estimated from the mediolateral oblique view using Cumulus, a computer-assisted thresholding program. Linear mixed effects models incorporating familial correlation were used to assess the association of risk factors with percent density, adjusting for age, weight, and other breast cancer risk factors, all at time of mammography.

Results: The mean age at mammography was 60.4 years (range, 40-91 years), and 76% were postmenopausal. Among postmenopausal women, there was a positive association of birthweight with percent density (P trend <0.01), with an adjusted mean percent density of 17.1% for <2.95 kg versus 21.0% for 3.75 kg. There were suggestive positive associations with gestational age (mean percent density of 16.7% for preterm birth, 20.2% for term birth, and 23.0% for late birth; P trend = 0.07), maternal eclampsia/preeclampsia (mean percent density of 19.9% for no and 14.6% for yes; P = 0.16), and being breast-fed as an infant (mean percent density of 18.2% for never and 20.0% for ever; P = 0.08). There was no association of percent density with maternal age, birth order, maternal use of alcohol or cigarettes, or neonatal jaundice. Except for being breast-fed, these associations showed similar but attenuated trends among premenopausal women, although none were statistically significant. The results for dense area paralleled the percent density results. The associations of gestational age and being breast-fed as an infant with percent density attenuated when included in the same model as birthweight.

Conclusions: Birthweight was positively associated with mammographic breast density and dense area among postmenopausal women and more weakly among premenopausal women, suggesting that it may be a marker of this early life exposure. These results offer some support to the hypothesis that pregnancy estrogens or other pregnancy changes may play a role in breast cancer etiology, and suggest that these factors may act in part through long-term effects on breast density.

This article has been cited by other articles:

				T. Tot The Theory of the Sick Breast Lobe and the Possible Consequences International Journal of Surgical Pathology, October 1, 2007; 15(4): 369 - 375. [Abstract] [PDF]

				T. Sellers, C. Vachon, V. Pankratz, C. Janney, Z Fredericksen, K. Brandt, Y Huang, F. Couch, L. Kushi, and J. Cerhan Association of Childhood and Adolescent Anthropometric Factors, Physical Activity, and Diet with Adult Mammographic Breast Density Am. J. Epidemiol., August 15, 2007; 166(4): 456 - 464. [Abstract] [Full Text] [PDF]

				J. E. Olson, C. X. Ma, L. L. Pelleymounter, D. J. Schaid, V. S. Pankratz, R. A. Vierkant, Z. S. Fredericksen, J. N. Ingle, Y. Wu, F. Couch, et al. A Comprehensive Examination of CYP19 Variation and Breast Density Cancer Epidemiol. Biomarkers Prev., March 1, 2007; 16(3): 623 - 625. [Full Text] [PDF]

				J. A. Knight, C. M. Vachon, R. A. Vierkant, R. Vieth, J. R. Cerhan, and T. A. Sellers No association between 25-hydroxyvitamin d and mammographic density. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1988 - 1992. [Abstract] [Full Text] [PDF]

				L. E. Kelemen Food frequency questionnaires: not irrelevant yet. Cancer Epidemiol. Biomarkers Prev., May 1, 2006; 15(5): 1054 - 1054. [Full Text] [PDF]

				J. A. Ross High Birthweight and Cancer: Evidence and Implications Cancer Epidemiol. Biomarkers Prev., January 1, 2006; 15(1): 1 - 2. [Full Text] [PDF]

				H. J. Baer, S. J. Schnitt, J. L. Connolly, C. Byrne, W. C. Willett, B. Rosner, and G. A. Colditz Early Life Factors and Incidence of Proliferative Benign Breast Disease Cancer Epidemiol. Biomarkers Prev., December 1, 2005; 14(12): 2889 - 2897. [Abstract] [Full Text] [PDF]