背景:前瞻性流行病学研究一致表明,绝经后妇女的循环雄激素水平与乳腺癌风险呈正相关。然而,绝经前妇女的数据有限.
方法:在纽约大学妇女健康研究中进行了一项病例对照研究。共包括356例(276例侵入性和80例原位)和683例单独匹配的对照。匹配变量包括年龄和日期,阶段,和献血的月经周期。睾酮,雄烯二酮,使用直接免疫测定法测定硫酸脱氢雄酮(DHEAS)和性激素结合球蛋白(SHBG)。计算游离睾酮。
结果:绝经前血清睾酮和游离睾酮浓度与乳腺癌风险呈正相关。在根据已知的乳腺癌危险因素调整的模型中,睾酮增加五分位数的比值比为1.0(参考),1.5(95%置信区间(CI),0.9to2.3),1.2(95%CI,0.7至1.9),1.4(95%CI,0.9至2.3)和1.8(95%CI,1.1至2.9;P趋势=0.04),游离睾酮为1.0(参考),1.2(95%CI,0.7至1.8),1.5(95%CI,0.9至2.3),1.5(95%CI,0.9至2.3),和1.8(95%CI,1.1至2.8,P趋势=0.01)。与雄烯二酮有轻微显著的正相关(P=0.07)。但与DHEAS或SHBG无关。结果在按肿瘤类型分层的分析中一致(侵入性,insitu),雌激素受体状态,献血的年龄,和诊断时的绝经状态。在138例病例和268例对照中,间隔0.8至5.3年(中位数为2年)收集的样本的类别内相关系数除雄烯二酮(对照中为0.57)外,所有生物标志物均大于0.7。
结论:绝经前睾酮和游离睾酮浓度与乳腺癌风险相关。睾酮和游离睾酮测量也是高度可靠的(即,一个单一的测量反映了一个女人随着时间的推移的平均水平)。其他前瞻性研究的结果与我们的结果一致。应评估40至50岁女性乳腺癌风险预测模型中包括睾酮或游离睾酮的影响。改善该年龄组的风险预测模型可以帮助有关乳腺癌筛查和化学预防的决策。
BACKGROUND: Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited.
METHODS: A
case-control study nested within the New York University Women\'s Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone,
androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated.
RESULTS: Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with
androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for
androstenedione (0.57 in controls).
CONCLUSIONS: Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman\'s average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.