Affiliations of authors: San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (GNF, NP, SRC); Faculty of Health Sciences, University of Balamand, Beirut, Lebanon (GNF); Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (GA, AZL); Department of Internal Medicine, University of California-San Francisco, San Francisco, CA (AH, DG); Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA (EV); Department of Internal Medicine, University of California-Davis, Sacramento, CA (JSL); Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (JAC); Department of Internal Medicine, Ohio State University, Columbus, OH (RJ); Department of Preventive Medicine, Stony Brook University, Stony Brook, NY (DL); Department of Medicine, Emory University, Atlanta, GA (LP); Karmanos Cancer Institute, Wayne State University, Detroit, MI (MSS).
J Natl Cancer Inst. 2013 Oct 2;105(19):1496-503. doi: 10.1093/jnci/djt243. Epub 2013 Sep 16.
Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer.
We conducted a nested case-control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone-binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided.
Statistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol (P trend = .04), bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P < .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; P interaction = .04).
Women with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings.
虽然内源性性激素水平较高和雌激素加孕激素（E+P）治疗与乳腺癌风险增加相关，但尚不清楚性激素的预处理水平是否会改变 E+P 对乳腺癌的作用。
我们在 E+P 的妇女健康倡议随机临床试验中进行了嵌套病例对照研究。该试验纳入了 16608 名年龄在 50 至 79 岁、子宫完整且无乳腺癌病史的绝经后妇女。在平均 5.6 年的随访期间，发现了 348 例新发乳腺癌病例，并与 348 名对照匹配。使用敏感测定法，在基线（雌激素、睾酮、孕酮和性激素结合球蛋白 [SHBG]）和第 1 年（雌激素和 SHBG）测量病例和对照的性激素水平。所有统计检验均为双侧。
总雌二醇（P 趋势 =.04）、生物可用雌二醇（P 趋势 =.03）、雌酮（P 趋势 =.007）和雌酮硫酸盐（P 趋势 =.007）的预处理水平升高与乳腺癌风险显著升高相关。E+P 在第 1 年增加了所有测量的雌激素和 SHBG（所有 P <.001）。E+P 对乳腺癌风险的影响在总雌二醇、生物可用雌二醇和雌酮预处理水平最低的女性中最强。例如，与最高总雌二醇四分位数相比，最低总雌二醇四分位数中 E+P 相对于安慰剂的比值比为 2.47（95%置信区间 [CI] = 1.28 至 4.79），而最高总雌二醇四分位数为 0.96（95% CI = 0.44 至 2.09）；P 交互 =.04）。
与内源性雌激素水平较高的女性相比，E+P 治疗期间，预处理雌激素水平较低的女性患乳腺癌的风险更高。需要进一步的研究来证实这些发现。
