Byrne Celia, Ursin Giske, Martin Christopher F, Peck Jennifer D, Cole Elodia B, Zeng Donglin, Kim Eunhee, Yaffe Martin D, Boyd Norman F, Heiss Gerardo, McTiernan Anne, Chlebowski Rowan T, Lane Dorothy S, Manson JoAnn E, Wactawski-Wende Jean, Pisano Etta D
Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Cancer Registry of Norway, Institute of Population Based Cancer Research, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
J Natl Cancer Inst. 2017 Sep 1;109(9). doi: 10.1093/jnci/djx001.
Estrogen plus progestin therapy increases both mammographic density and breast cancer incidence. Whether mammographic density change associated with estrogen plus progestin initiation predicts breast cancer risk is unknown.
We conducted an ancillary nested case-control study within the Women's Health Initiative trial that randomly assigned postmenopausal women to daily conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg or placebo. Mammographic density was assessed from mammograms taken prior to and one year after random assignment for 174 women who later developed breast cancer (cases) and 733 healthy women (controls). Logistic regression analyses included adjustment for confounders and baseline mammographic density when appropriate.
Among women in the estrogen plus progestin arm (97 cases/378 controls), each 1% positive change in percent mammographic density increased breast cancer risk 3% (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01 to 1.06). For women in the highest quintile of mammographic density change (>19.3% increase), breast cancer risk increased 3.6-fold (95% CI = 1.52 to 8.56). The effect of estrogen plus progestin use on breast cancer risk (OR = 1.28, 95% CI = 0.90 to 1.82) was eliminated in this study, after adjusting for change in mammographic density (OR = 1.00, 95% CI = 0.66 to 1.51).
We found the one-year change in mammographic density after estrogen plus progestin initiation predicted subsequent increase in breast cancer risk. All of the increased risk from estrogen plus progestin use was mediated through mammographic density change. Doctors should evaluate changes in mammographic density with women who initiate estrogen plus progestin therapy and discuss the breast cancer risk implications.
雌激素加孕激素疗法会增加乳腺钼靶密度以及乳腺癌发病率。与开始使用雌激素加孕激素相关的乳腺钼靶密度变化是否能预测乳腺癌风险尚不清楚。
我们在女性健康倡议试验中进行了一项辅助性巢式病例对照研究，该试验将绝经后女性随机分配至每日服用 0.625 毫克结合马雌激素加 2.5 毫克醋酸甲羟孕酮或安慰剂组。对 174 名后来患乳腺癌的女性（病例组）和 733 名健康女性（对照组），在随机分组前及分组后一年拍摄的乳腺钼靶片评估乳腺钼靶密度。逻辑回归分析在适当情况下对混杂因素和基线乳腺钼靶密度进行了调整。
在雌激素加孕激素组的女性中（97 例病例/378 例对照），乳腺钼靶密度百分比每增加 1%，乳腺癌风险增加 3%（比值比[OR]=1.03，95%置信区间[CI]=1.01 至 1.06）。对于乳腺钼靶密度变化处于最高五分位数（增加>19.3%）的女性，乳腺癌风险增加 3.6 倍（95%CI=1.52 至 8.56）。在调整了乳腺钼靶密度变化后（OR=1.00，95%CI=0.66 至 1.51），本研究中使用雌激素加孕激素对乳腺癌风险的影响（OR=1.28，95%CI=0.90 至 1.82）被消除。
我们发现开始使用雌激素加孕激素后一年的乳腺钼靶密度变化可预测随后乳腺癌风险的增加。使用雌激素加孕激素带来的所有风险增加均通过乳腺钼靶密度变化介导。医生应对开始雌激素加孕激素治疗的女性评估乳腺钼靶密度变化，并讨论其对乳腺癌风险的影响。
