Abstract
IntroductionSex and growth hormones are positively associated with postmenopausal breast cancer risk. However, few studies have evaluated the influence of multiple hormones simultaneously.MethodsWe considered the roles of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate and prolactin and, secondarily, insulin-like growth factor 1 (IGF-1) and c-peptide in postmenopausal breast cancer risk among 265 cases and 541 controls in the prospective Nurses' Health Study. We created several hormone scores, including ranking women by the number of hormones above the age- and batch-adjusted geometric mean and weighting hormone values by their individual associations with breast cancer risk.ResultsWomen in the top versus bottom quintile of individual estrogen or androgen levels had approximately a doubling of postmenopausal breast cancer risk. Having seven or eight compared to zero hormones above the geometric mean level was associated with total (RR = 2.7, 95% CI = 1.3 to 5.7, P trend < 0.001) and estrogen receptor (ER)-positive (RR = 3.4, 95% CI = 1.3 to 9.4, P trend < 0.001) breast cancer risk. When comparing the top versus bottom quintiles of the score weighted by individual hormone associations, the RR for total breast cancer was 3.0 (95% CI = 1.8 to 5.0, P trend < 0.001) and the RR for ER-positive disease was 3.9 (95% CI = 2.0 to 7.5, P trend < 0.001). The risk further increased when IGF-1 and c-peptide were included in the scores. The results did not change with adjustment for body mass index.ConclusionsOverall, the results of our study suggest that multiple hormones with high circulating levels substantially increase the risk of breast cancer, particularly ER-positive disease. Additional research should consider the potential impact of developing risk prediction scores that incorporate multiple hormones.
Highlights
Sex and growth hormones are positively associated with postmenopausal breast cancer risk
To assess this hypothesis and to extend the concept of developing hormone scores, we evaluated the role of multiple hormones on postmenopausal breast cancer risk using data from 265 patients and 541 controls in the prospective Nurses’ Health Study (NHS) who had measures of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and prolactin
Prolactin was suggestively associated with estrogen receptor (ER)-positive breast cancer risk (RR = 1.7), but associations for insulin-like growth factor 1 (IGF-1) and c-peptide were not statistically significant
Summary
Sex and growth hormones are positively associated with postmenopausal breast cancer risk. Several studies have assessed the joint effects of sex and growth hormones on postmenopausal breast cancer all hormones had a substantially lower risk of breast cancer compared to women with one or more hormone levels above the mean (RR = 0.11, 95% CI = 0.01 to 0.90). The authors suggested that mammotropic hormones may act as permissive factors for breast cancer growth To assess this hypothesis and to extend the concept of developing hormone scores, we evaluated the role of multiple hormones on postmenopausal breast cancer risk using data from 265 patients and 541 controls in the prospective Nurses’ Health Study (NHS) who had measures of estrone, estradiol, estrone sulfate, testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEAS and prolactin. We considered a subset of women who had IGF-1 and c-peptide measures
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