Circulating Sex Steroid Levels, Mammographic Density May Predict Breast Cancer

August 27, 2007 — Circulating sex steroid levels and mammographic density were strongly and independently associated with the risk for breast cancer in postmenopausal women, according to the results of a nested case-control study in the August 1 issue of the Journal of the National Cancer Institute.
"Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk," write Rulla M. Tamimi, ScD, from the Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues. "Whether mammographic density reflects levels of endogenous sex hormones is unclear. We examined whether these predictors are independently associated with breast cancer risk in a prospective study."
This nested case-control study within the Nurses' Health Study cohort included 253 case subjects with breast cancer and 520 control subjects. All subjects were postmenopausal women, none of whom were using postmenopausal hormone therapy at the time of blood sampling or mammography.
Blood was drawn for plasma levels of estradiol, free estradiol, testosterone, and free testosterone, and computer-assisted analysis of mammograms allowed evaluation of mammographic density. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated from logistic regression models adjusted for matching variables and potential confounders.
Levels of circulating sex steroids and mammographic density were independently and statistically significantly associated with the risk for breast cancer. Compared with the lowest quartile of mammographic density, the highest quartile was associated with an RR for breast cancer of 3.8 (95% CI, 2.2 - 6.6; P for trend <.001).
This RR did not change by much when the analysis was adjusted for circulating estradiol (RR, 3.9; 95% CI, 2.2 - 6.9; P for trend <.001) or for circulating testosterone (RR, 4.1; 95% CI, 2.3 - to 7.2; P for trend <.001).
Both before and after adjustment for mammographic density, circulating levels of estradiol (RR, 2.4; 95% CI, 1.4 - 4.0) and of testosterone (RR, 2.0; 95% CI, 1.2 - 3.1) were both associated with the risk for breast cancer. A joint analysis of mammographic density and plasma testosterone revealed that the risk for breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both (RR, 6.0; 95% CI, 2.6 - 14.0). Joint analysis of estradiol and mammographic density revealed a similar pattern (RR, 4.1; 95% CI, 1.7 - 9.8).
Limitations of the study include circulating levels of steroid hormones used as a marker for levels of steroid hormones in breast tissues, lower sensitivity of mammography in women with denser breasts, inability to collect mammograms from all women in the nested case-control study, and minor differences in rates of success according to case-control status.
"Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women," the study authors write. "Future studies should examine this relationship among premenopausal women, especially with respect to follicular estradiol levels, because levels during this phase have been reported to be associated with subsequent risk of breast cancer."
The National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Breast Cancer Research Fund, and American Cancer Society funded this study.
J Natl Cancer Inst. 2007;99:1178-1187.