绝经后女性的内源性激素水平、乳腺钼靶密度及后续患乳腺癌的风险。

Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women.

作者信息

Tamimi Rulla M, Byrne Celia, Colditz Graham A, Hankinson Susan E

机构信息

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA.

出版信息

J Natl Cancer Inst. 2007 Aug 1;99(15):1178-87. doi: 10.1093/jnci/djm062. Epub 2007 Jul 24.

DOI:10.1093/jnci/djm062

PMID:17652278

Abstract

BACKGROUND

Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk. Whether mammographic density reflects levels of endogenous sex hormones is unclear. We examined whether these predictors are independently associated with breast cancer risk in a prospective study.

METHODS

We conducted a nested case-control study within the Nurses' Health Study cohort of 253 case subjects with breast cancer and 520 control subjects. All participants were postmenopausal women who were not using postmenopausal hormones at the time of both blood collection and mammography. Plasma levels of estradiol, free estradiol, testosterone, and free testosterone were evaluated. Mammographic density was assessed by use of computer-assisted analysis of mammograms. Logistic regression models that were adjusted for matching variables and potential confounders were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.

RESULTS

Levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk. The relative risk of breast cancer associated with mammographic density (RR for highest quartile compared with lowest quartile = 3.8, 95% CI = 2.2 to 6.6; P(trend)<.001) changed little when the analysis was adjusted for circulating estradiol (RR = 3.9, 95% CI = 2.2 to 6.9; P(trend)<.001) or circulating testosterone (RR = 4.1, 95% CI = 2.3 to 7.2; P(trend)<.001). Circulating levels of estradiol (RR = 2.4, 95% CI = 1.4 to 4.0) and of testosterone (RR = 2.0, 95% CI = 1.2 to 3.1) were both associated with breast cancer risk, before and after adjustment for mammographic density. In a joint analysis of mammographic density and plasma testosterone, the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both (RR = 6.0, 95% CI = 2.6 to 14.0). A similar pattern was observed in the joint analysis of estradiol and mammographic density (RR = 4.1, 95% CI = 1.7 to 9.8).

CONCLUSIONS

Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women.

摘要

背景

乳腺钼靶密度和循环性激素是乳腺癌风险的两个已得到充分证实的预测指标。乳腺钼靶密度是否反映内源性性激素水平尚不清楚。我们在一项前瞻性研究中检验了这些预测指标是否与乳腺癌风险独立相关。

方法

我们在护士健康研究队列中进行了一项巢式病例对照研究，纳入253例乳腺癌病例和520例对照。所有参与者均为绝经后女性，在采血和乳腺钼靶检查时均未使用绝经后激素。评估血浆雌二醇、游离雌二醇、睾酮和游离睾酮水平。通过计算机辅助分析乳腺钼靶片评估乳腺钼靶密度。使用针对匹配变量和潜在混杂因素进行调整的逻辑回归模型计算相对风险（RR）和95%置信区间（CI）。所有统计检验均为双侧检验。

结果

循环性激素水平和乳腺钼靶密度均与乳腺癌风险在统计学上显著且独立相关。在针对循环雌二醇（RR = 3.9，95% CI = 2.2至6.9；P趋势<.001）或循环睾酮（RR = 4.1，95% CI = 2.3至7.2；P趋势<.001）进行分析调整后，与乳腺钼靶密度相关的乳腺癌相对风险（最高四分位数与最低四分位数相比的RR = 3.8，95% CI = 2.2至6.6；P趋势<.001）变化不大。在调整乳腺钼靶密度之前和之后，循环雌二醇水平（RR = 2.4，95% CI = 1.4至4.0）和睾酮水平（RR = 2.0，95% CI = 1.2至3.1）均与乳腺癌风险相关。在乳腺钼靶密度和血浆睾酮的联合分析中，相对于两者的最低三分位数，两者最高三分位数的乳腺癌风险最高（RR = 6.0，95% CI = 2.6至14.0）。在雌二醇和乳腺钼靶密度的联合分析中观察到类似模式（RR = 4.1，95% CI = 1.7至9.8）。