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Abstract：
OBJECTIVE: Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways.
METHODS: This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders.
RESULTS: Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05).
CONCLUSIONS: Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.
METHODS: This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders.
RESULTS: Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05).
CONCLUSIONS: Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.
摘要：
目的：性激素与绝经后乳腺癌相关，但很少考虑其他生物学途径的潜在混杂因素。我们估计性激素生物标志物与绝经后雌激素受体（ER）阳性乳腺癌的风险比，同时考虑来自胰岛素/胰岛素样生长因子信号传导和炎症途径的生物标志物。
方法：该分析包括来自墨尔本协作队列研究中绝经后乳腺癌病例队列研究的1208名女性。使用具有稳健方差估计的加权泊松回归来估计绝经后ER阳性乳腺癌的风险比（RR）和95％置信区间（CI）。孕酮的每倍增血浆浓度，雌激素,雄激素,和性激素结合球蛋白（SHBG）。分析包括社会人口统计学和生活方式混杂因素，和其他被确定为潜在混杂因素的生物标志物。
结果：孕酮血浆浓度每增加一倍，绝经后ER阳性乳腺癌的风险增加（RR：1.22，95％CI1.03至1.44），雄烯二酮（RR1.20，95%CI0.99至1.45），脱氢表雄酮（RR：1.15，95%CI1.00至1.34），总睾酮（RR：1.11，95%CI0.96至1.29），游离睾酮（RR：1.12，95%CI0.98至1.28），雌酮(RR1.21，95%CI0.99至1.48)，总雌二醇（RR1.19，95%CI1.02至1.39）和游离雌二醇（RR1.22，95%CI1.05至1.41）。SHBG的风险可能降低（RR0.83，95％CI0.66至1.05）。
结论：孕酮，雌激素和雄激素可能会增加绝经后ER阳性乳腺癌的风险，而SHBG可能降低风险。这些发现加强了绝经后乳腺癌性激素驱动性质的因果证据。
方法：该分析包括来自墨尔本协作队列研究中绝经后乳腺癌病例队列研究的1208名女性。使用具有稳健方差估计的加权泊松回归来估计绝经后ER阳性乳腺癌的风险比（RR）和95％置信区间（CI）。孕酮的每倍增血浆浓度，雌激素,雄激素,和性激素结合球蛋白（SHBG）。分析包括社会人口统计学和生活方式混杂因素，和其他被确定为潜在混杂因素的生物标志物。
结果：孕酮血浆浓度每增加一倍，绝经后ER阳性乳腺癌的风险增加（RR：1.22，95％CI1.03至1.44），雄烯二酮（RR1.20，95%CI0.99至1.45），脱氢表雄酮（RR：1.15，95%CI1.00至1.34），总睾酮（RR：1.11，95%CI0.96至1.29），游离睾酮（RR：1.12，95%CI0.98至1.28），雌酮(RR1.21，95%CI0.99至1.48)，总雌二醇（RR1.19，95%CI1.02至1.39）和游离雌二醇（RR1.22，95%CI1.05至1.41）。SHBG的风险可能降低（RR0.83，95％CI0.66至1.05）。
结论：孕酮，雌激素和雄激素可能会增加绝经后ER阳性乳腺癌的风险，而SHBG可能降低风险。这些发现加强了绝经后乳腺癌性激素驱动性质的因果证据。
