Schwartz Ann G, Ray Roberta M, Cote Michele L, Abrams Judith, Sokol Robert J, Hendrix Susan L, Chen Chu, Chlebowski Rowan T, Hubbell F Allan, Kooperberg Charles, Manson JoAnn E, O'Sullivan Mary Jo, Rohan Thomas, Stefanick Marcia L, Wactawski-Wende Jean, Wakelee Heather, Simon Michael S
*Karmanos Cancer Institute and Department of Oncology, Wayne State University, Detroit, Michigan; †Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle Washington; ‡C.S. Mott Center for Human Growth and Development and Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan; §St. Joseph Mercy Oakland Hospital, Pontiac, Michigan; ‖Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; ¶Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California; #Department of Medicine, University of California, Irvine, California; **Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; ††Department of Obstetrics and Gynecology, University of Miami School of Medicine, Miami, Florida; ‡‡Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York; §§Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California; ‖‖Department of Epidemiology and Environmental Health, University of Buffalo School of Public Health and Health Professions, Buffalo, New York; and ¶¶Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford Cancer Institute, Stanford, California.
J Thorac Oncol. 2015 Jul;10(7):1004-13. doi: 10.1097/JTO.0000000000000558.
Results from the Women's Health Initiative clinical trials demonstrated no increase in the risk of lung cancer in postmenopausal women treated with hormone therapy (HT). We conducted a joint analysis of the Women's Health Initiative observational study data and clinical trials data to further explore the association between estrogen and estrogen-related reproductive factors and lung cancer risk.
Reproductive history, oral contraceptive use, and postmenopausal HT were evaluated in 160,855 women with known HT exposures. Follow-up for lung cancer was through September 17, 2012; 2467 incident lung cancer cases were ascertained, with median follow-up of 14 years.
For all lung cancers, women with previous use of estrogen plus progestin of less than 5 years (hazard ratio = 0.84; 95% confidence interval = 0.71-0.99) were at reduced risk. A limited number of reproductive factors demonstrated associations with risk. There was a trend toward decreased risk with increasing age at menopause (ptrend = 0.04) and a trend toward increased risk with increasing number of live births (ptrend = 0.03). Reduced risk of non-small-cell lung cancer was associated with age 20-29 years at first live birth. Risk estimates varied with smoking history, years of HT use and previous bilateral oophorectomy.
Indirect measures of estrogen exposure to lung tissue, as used in this study, provide only weak evidence for an association between reproductive history or HT use and risk of lung cancer. More detailed mechanistic studies and evaluation of risk factors in conjunction with estrogen receptor expression in the lung should continue as a role for estrogen cannot be ruled out and may hold potential for prevention and treatment strategies.
妇女健康倡议临床试验结果表明，接受激素治疗（HT）的绝经后女性患肺癌的风险并未增加。我们对妇女健康倡议观察性研究数据和临床试验数据进行了联合分析，以进一步探讨雌激素及雌激素相关生殖因素与肺癌风险之间的关联。
在160,855名已知有HT暴露情况的女性中评估其生殖史、口服避孕药使用情况及绝经后HT情况。肺癌随访至2012年9月17日；确定了2467例肺癌发病病例，中位随访时间为14年。
对于所有肺癌，既往使用雌激素加孕激素少于5年的女性（风险比=0.84；95%置信区间=0.71-0.99）风险降低。少数生殖因素显示与风险有关联。随着绝经年龄增加风险有降低趋势（趋势P值=0.04），随着活产数增加风险有增加趋势（趋势P值=0.03）。首次活产年龄在20-29岁与非小细胞肺癌风险降低有关。风险估计因吸烟史、HT使用年限及既往双侧卵巢切除术而有所不同。
本研究中所采用的对肺组织雌激素暴露的间接测量方法，仅提供了微弱证据证明生殖史或HT使用与肺癌风险之间存在关联。由于不能排除雌激素的作用且其可能在预防和治疗策略方面具有潜力，因此应继续开展更详细的机制研究以及结合肺组织中雌激素受体表达对风险因素进行评估。
