Purpose

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).

Conclusion

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.

中文翻译：

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性类固醇激素与绝经后雌激素受体阳性乳腺癌的风险：病例队列分析

目的

性类固醇激素与绝经后乳腺癌有关，但很少考虑其他生物途径的潜在混淆。我们估计了与绝经后雌激素受体（ER）阳性乳腺癌相关的性类固醇激素生物标志物的风险比，同时考虑了胰岛素/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

该分析纳入了墨尔本合作队列研究中绝经后乳腺癌病例队列研究的 1208 名女性。使用稳健方差估计器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)，每倍血浆孕酮、雌激素、雄激素和性激素结合球蛋白浓度（性激素结合球蛋白）。分析包括社会人口统计学和生活方式混杂因素，以及被确定为潜在混杂因素的其他生物标志物。

结果

孕酮（RR：1.22，95％CI 1.03至1.44）、雄烯二酮（RR：1.20，95％CI 0.99至1.45）、脱氢表雄酮（RR：1.15，95）血浆浓度每增加一倍，绝经后ER阳性乳腺癌的风险就会增加。 % CI 1.00 至 1.34)、总睾酮（RR：1.11，95% CI 0.96 至 1.29）、游离睾酮（RR：1.12，95% CI 0.98 至 1.28）、雌酮（RR 1.21，95% CI 0.99 至 1.48）、总雌二醇（RR 1.19，95% CI 1.02 至 1.39）和游离雌二醇（RR 1.22，95% CI 1.05 至 1.41）。观察到 SHBG 的风险可能降低（RR 0.83，95% CI 0.66 至 1.05）。

结论

黄体酮、雌激素和雄激素可能会增加绝经后 ER 阳性乳腺癌的风险，而性激素结合球蛋白 (SHBG) 可能会降低风险。这些发现强化了有关绝经后乳腺癌性激素驱动性质的因果证据。