Introduction: During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer. Methods: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25-29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV. Results: Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all Ptrend ≤0.03) but not when measured in postmenarche samples (all Ptrend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all Ptrend ≥0.16). Conclusions: Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown. Clinical trials registration: ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999.
Bibliographical noteFunding Information:
This work was supported by US National Institutes of Health (NIH) grants (R03 CA167764 to J.F. Dorgan, R01 CA104670 to J.F. Dorgan, R01 CA116182 to N.M. Hylton, and P30 CA134274 to K.J. Cullen). We thank the institutional review board at Maryland Medical Research Institute, University of Maryland Baltimore, MD, Fox Chase Cancer Center, Philadelphia, PA and the following six clinical centers: Children’s Hospital, New Orleans, LA; Johns Hopkins University Hospital, Baltimore, MD; Kaiser Permanente Center for Health Research, Portland, OR; University of Medicine and Dentistry of New Jersey, Newark, NJ; Northwestern University Medical School, Chicago, IL; and University of Iowa Hospital and Clinics, Iowa City, IA. We are grateful to all participants in the DISC06 study and collaborators for their invaluable contributions.
© 2015 Jung et al.