Vachon Celine M, Sellers Thomas A, Vierkant Robert A, Wu Fang-Fang, Brandt Kathleen R
Department of Health Sciences Research, Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1382-8.
Previous studies have demonstrated an association between current hormone replacement therapy (HRT) use and increased mammographic breast density. Many of these studies have also shown that only 20-35% of women initiating HRT respond in this manner. This subgroup of HRT responders may be at an increased risk of breast cancer. We performed a case-control study to investigate how women who experience increased density in response to HRT (cases) differ from women who do not experience an increase in density with HRT use (controls) with regard to breast cancer risk factors, type of HRT, weight change, and baseline breast density. Participants were female residents of Olmsted County, Minnesota who received routine screening mammograms at the Mayo Clinic. Cases included 172 women identified between the years 1998 and 1999 by Mayo radiologists as having a HRT response. Controls were women who did not experience an increase in mammographic density with HRT use and were matched to cases on age (+/-3 years), menopausal status, duration of HRT, month of initiation of HRT, and months between baseline and follow-up mammograms. Mammograms were obtained from cases and controls before and during HRT therapy. Breast density was read as a four-category Bi-Rads density grade measure and as a quantitative percentage estimate, using a computer-assisted method. Risk factor information was obtained from both chart review and a mammography database of patient-provided information. There was no association between HRT response and first-degree family history of breast cancer [odds ratio (OR), 0.8; 95% confidence interval (CI), 0.4-1.5], parity (OR, 0.8; 95% CI, 0.4-1.7), later age at first birth (OR, 0.8 for age >25 years versus nulliparous women; 95% CI, 0.4-1.8), or history of biopsy (OR, 0.9; 95% CI, 0.6-1.5). There was also no association with baseline weight or change in weight between a woman's baseline and follow-up mammograms. However, there was evidence of an association between HRT response and type of HRT used; women who experienced a mammographic increase in density with HRT had 2.3 greater odds (95% CI, 1.4-3.7) of having taken estrogen-progestin combined therapy than estrogen alone, compared with controls. This association was stronger among women with a baseline weight below the median (OR, 5.2; 95% CI, 1.6-17.6). Also, there was an inverse association between HRT response and baseline density. Because all risk factors examined accounted for only 26% of the variation in the HRT response, genes or other unmeasured factors are thought to be involved.
既往研究表明，目前使用激素替代疗法（HRT）与乳腺钼靶检查显示的乳房密度增加之间存在关联。这些研究中的许多还表明，开始使用HRT的女性中只有20%-35%会出现这种情况。这一HRT反应亚组的女性患乳腺癌的风险可能会增加。我们进行了一项病例对照研究，以调查因HRT而乳房密度增加的女性（病例组）与使用HRT但乳房密度未增加的女性（对照组）在乳腺癌风险因素、HRT类型、体重变化和基线乳房密度方面有何不同。研究对象为明尼苏达州奥尔姆斯特德县的女性居民，她们在梅奥诊所接受常规乳腺钼靶筛查。病例组包括1998年至1999年间被梅奥诊所放射科医生认定有HRT反应的172名女性。对照组是使用HRT后乳房钼靶密度未增加的女性，她们在年龄（±3岁）、绝经状态、HRT持续时间、开始使用HRT的月份以及基线与随访乳腺钼靶检查之间的月份等方面与病例组相匹配。在HRT治疗前和治疗期间获取病例组和对照组的乳腺钼靶图像。使用计算机辅助方法将乳房密度读取为四类乳腺影像报告和数据系统（Bi-Rads）密度分级测量值以及定量百分比估计值。通过病历审查和患者提供信息的乳腺钼靶数据库获取风险因素信息。HRT反应与乳腺癌一级家族史[比值比（OR），0.8；95%置信区间（CI），0.4-1.5]、产次（OR，0.8；95%CI，0.4-1.7）、初产年龄较大（初产年龄>25岁的女性与未生育女性相比，OR为0.8；95%CI，0.4-1.8）或活检史（OR，0.9；95%CI，0.6-1.5）之间均无关联。女性的基线体重或基线与随访乳腺钼靶检查之间的体重变化也无关联。然而，有证据表明HRT反应与所使用的HRT类型之间存在关联；与对照组相比，使用HRT后乳房钼靶密度增加的女性接受雌孕激素联合治疗的几率比仅使用雌激素高2.3倍（95%CI，1.4-3.7）。这种关联在基线体重低于中位数的女性中更强（OR，5.2；95%CI，1.6-17.6）。此外，HRT反应与基线密度之间存在负相关。由于所检查的所有风险因素仅占HRT反应变异的26%，因此认为基因或其他未测量的因素也参与其中。
