性激素水平与雌激素受体阴性和雌激素受体阳性乳腺癌的风险。
Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers.
机构信息
San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
出版信息
J Natl Cancer Inst. 2011 Apr 6;103(7):562-70. doi: 10.1093/jnci/djr031. Epub 2011 Feb 17.
BACKGROUND
Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear.
METHODS
In a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided.
RESULT
The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors.
CONCLUSION
Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.
背景
内源性性激素水平与乳腺癌的总体风险以及雌激素受体（ER）阳性乳腺癌有关；然而，它们与 ER 阴性肿瘤的关系仍不清楚。
方法
在绝经后 50-79 岁的妇女健康倡议观察研究中的病例-对照研究中，我们研究了生物可利用的睾酮和雌二醇水平与 ER 阴性和 ER 阳性乳腺癌风险之间的关系。在 317 名浸润性乳腺癌病例受试者和 594 名女性的亚组中，在基线访视时评估了生物可利用的睾酮和雌二醇水平。使用总激素水平和性激素结合球蛋白浓度（分别通过放射免疫测定和化学发光免疫测定测量）计算生物可利用的性激素水平。使用 Cox 比例风险回归进行统计分析。所有统计检验均为双侧检验。
结果
未经调整的 ER 阴性乳腺癌的绝对发生率分别为第 1-4 四分位睾酮水平的 0.34、0.20、0.23 和 0.21/10000 人年。与睾酮水平最低四分位的女性相比，四分位 2 的女性 ER 阴性癌症的风险降低了 56%（风险比[HR] = 0.44，95%置信区间[CI] = 0.23 至 0.85），四分位 3 的风险降低了 45%（HR = 0.55，95%CI = 0.30 至 1.01），四分位 4 的风险降低了 49%（HR = 0.51，95%CI = 0.28 至 0.94），独立于其他风险因素。雌二醇水平与 ER 阴性乳腺癌无关。ER 阳性乳腺癌风险随睾酮水平升高而增加（P（趋势）=.04），但调整雌二醇后该趋势无统计学意义（P（趋势）=.15）。与四分位 1 的女性相比，雌二醇水平在四分位 2-4 的女性中，ER 阳性癌症的风险大约高出两倍，独立于风险因素。
结论
绝经后妇女血清中生物可利用的睾酮水平较高与 ER 阴性乳腺癌的风险降低有关。
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