Exposure to higher levels of endogenous hormones associated with increased breast cancer risk

The association between endogenous hormones and postmenopausal breast cancer risk are independent of tumor grade and hormone receptor status, and may increase in intensity with age, according to new study findings.

Researchers in Australia assessed the association of circulating hormone levels with overall risk for breast cancer in 857 naturally postmenopausal women and 197 breast cancer cases diagnosed during 9.2 years of follow-up (mean age at diagnosis, 67 years). All were enrolled in the Melbourne Collaborative Cohort study. Information on breast cancer grade was available for 176 cases, including 22% well differentiated, 47% moderately differentiated and 31% poorly differentiated.

The researchers measured concentrations of total estradiol, estrone sulfate, testosterone, dehydroepiandrosterone sulfate, androstenedione and sex hormone-binding globulin at baseline before diagnosis, and calculated free estradiol plasma concentration.

The HR was higher for women with higher concentrations of all estrogens and androgens. However, the test for trend was statistically significant for free estradiol (HR=1.61; 95% CI, 1.12-2.33) and estrone sulfate (HR=1.52; 95% CI, 1.11-2.07).

When researchers compared the fourth and first quartiles, the HR for breast cancer was 1.44 for total estradiol (95% CI, 0.89-2.35), 1.75 for free estradiol (95% CI, 1.06-2.89), 2.05 for estrone sulfate (95% CI, 1.24-3.37), 1.25 for testosterone (95% CI, 0.78-2.01), 1.41 for dehydroepiandrosterone sulfate (95% CI, 0.88-2.27), 1.49 for androstenedione (95% CI, 0.91-2.44) and 0.33 for sex hormone-binding globulin (95% CI, 0.19-0.55). According to the researchers, these associations did not differ by tumor grade and estrogen receptor/progesterone receptor status.

Older age was associated with increased risk for higher levels of estrogen and androgen (P=.59 for total estradiol; P=.01 for testosterone).

Previous research suggested that hormone-related breast cancer risk factors may have a distinct effect on hormone receptor-positive tumors vs. hormone receptor-negative tumors. Moreover, postmenopausal exposure to exogenous hormones may increase the risk for estrogen receptor-positive tumors compared with estrogen receptor-negative tumors.

“Our prospective study confirms earlier findings that, for postmenopausal women, exposure to higher levels of endogenous hormones is associated with an increased risk for breast cancer and also suggests that the associations might be stronger for breast cancer diagnosed at older ages,” the researchers concluded.

Baglietto L. Can Epidem Bio Prev. 2010;19:1–11.