Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
Cancer Epidemiol Biomarkers Prev. 2020 May;29(5):1058-1066. doi: 10.1158/1055-9965.EPI-19-1302. Epub 2020 Mar 3.
Sex steroid hormones and sex hormone-binding globulin (SHBG) have been implicated in the etiology of invasive breast cancer, but their associations with risk of the precursor lesion, ductal carcinoma (DCIS) of the breast, remain unclear.
We used Cox proportional hazards regression models to estimate the associations of serum levels of estradiol (premenopausal women only), testosterone, and/or SHBG with DCIS risk among 182,935 women. After a median follow-up of 7.1 years, 186 and 531 DCIS cases were ascertained in premenopausal and postmenopausal women, respectively.
Total and free estradiol were positively associated with risk of DCIS among premenopausal women. The HRs for the highest versus the lowest tertiles were 1.54 (1.06-2.23) and 1.72 [95% confidence interval (CI), 1.15-2.57], respectively. Among postmenopausal women, elevated levels of free testosterone (FT), and to a lesser extent, total testosterone, were positively associated with DCIS risk. The HRs for the highest versus the lowest quartiles were 1.42 (95% CI, 1.09-1.85) and 1.16 (95% CI, 0.91-1.48), respectively. Serum SHBG levels were inversely associated with risk of DCIS among postmenopausal women (HR: 0.75; 95% CI, 0.56-0.99).
This study suggests that elevated levels of estradiol are associated with increased risk of DCIS among premenopausal women, and that among postmenopausal women, elevated levels of testosterone, and particularly those of FT, are associated with increased DCIS risk, while elevated levels of SHBG are associated with reduced risk.
These findings may be helpful in developing prevention strategies aimed at reducing breast cancer risk among premenopausal and postmenopausal women.
性激素和性激素结合球蛋白（SHBG）已被认为与浸润性乳腺癌的病因有关，但它们与乳腺癌前病变导管原位癌（DCIS）的风险之间的关系仍不清楚。
我们使用 Cox 比例风险回归模型来估计血清雌二醇（仅适用于绝经前妇女）、睾酮和/或 SHBG 水平与 182935 名妇女 DCIS 风险之间的关系。中位随访 7.1 年后，分别在绝经前和绝经后妇女中确定了 186 和 531 例 DCIS 病例。
总雌二醇和游离雌二醇与绝经前妇女的 DCIS 风险呈正相关。最高与最低三分位的 HR 分别为 1.54（1.06-2.23）和 1.72[95%置信区间（CI），1.15-2.57]。在绝经后妇女中，游离睾酮（FT）水平升高，并且在较小程度上总睾酮水平升高，与 DCIS 风险呈正相关。最高与最低四分位的 HR 分别为 1.42（95%CI，1.09-1.85）和 1.16（95%CI，0.91-1.48）。绝经后妇女的血清 SHBG 水平与 DCIS 风险呈负相关（HR：0.75；95%CI，0.56-0.99）。
本研究表明，绝经前妇女中雌二醇水平升高与 DCIS 风险增加有关，而绝经后妇女中睾酮水平升高，特别是 FT 水平升高与 DCIS 风险增加有关，而 SHBG 水平升高与风险降低有关。
这些发现可能有助于制定针对绝经前和绝经后妇女降低乳腺癌风险的预防策略。
