在婦女健康倡議（WHI）隨機研究中，研究者發(fā)現(xiàn)雌激素聯(lián)合黃體酮會增加女性乳腺癌發(fā)病率和死亡率,。與之相反,，絕大多數(shù)和雌激素聯(lián)合黃體酮有關(guān)的觀察性研究都指出這些乳腺癌患者的預(yù)后尚可。為了對上述問題進行進一步探討,，來自加利福尼亞州UCLA醫(yī)學(xué)中心的Rowan T. Chlebowski等選擇了與WHI臨床研究中受試者具有相同特征的受試者組成了WHI觀察性研究的受試者,，并探討了雌激素聯(lián)合黃體酮對乳腺癌患者發(fā)病率和死亡率的影響，他們的研究結(jié)果發(fā)表在JNCI 3月的在線期刊上,。
兩組患者確診后的生存時間
研究者納入了41449名絕經(jīng)后的女性作為受試者,，她們既往沒有接受過子宮切除術(shù)，并且在2年內(nèi)她們的鉬靶檢查結(jié)果未見明顯異常,。在這些女性中,，25328人不應(yīng)用激素，另有16121名女性聯(lián)合應(yīng)用雌激素和黃體酮,。研究者應(yīng)用了多變量調(diào)整后的Cox風(fēng)險比例回歸模型來計算危險比和95%可信區(qū)間,。所有的統(tǒng)計檢驗都在雙側(cè)進行。
在進行了約為111.3年的隨訪之后,，研究者發(fā)現(xiàn)2236名女性成為了乳腺癌患者,，與不應(yīng)用激素的女性相比，聯(lián)合應(yīng)用雌激素和黃體酮的女性的乳腺癌發(fā)病率更高,，分別為0.42%和0.60%,，HR為1.55，95%可信區(qū)間為1.41至1.70,，差異具有顯著統(tǒng)計學(xué)意義,。并且研究者發(fā)現(xiàn)在接近絕經(jīng)期時才開始應(yīng)用激素治療的女性乳腺癌發(fā)病風(fēng)險更高，隨著開始激素治療的時間距離絕經(jīng)期的延長發(fā)病風(fēng)險呈線性遞減,，結(jié)果同樣具有顯著統(tǒng)計學(xué)意義,。乳腺癌確診后的生存期（從確診時間至死亡）在兩組之間未有明顯的差異，HR為1.03,，95%可信區(qū)間為0.79至1.35,。從人群的角度來看，與未使用激素的女性相比,，聯(lián)合應(yīng)用雌激素和黃體酮組中的女性的死于乳腺癌的人數(shù)更多（HR為1.32,，95%可信區(qū)間為0.90至1.93），并且總體死亡數(shù)也更高（HR為1.65,，95%可信區(qū)間為1.29至2.12）,。
與WHI隨機研究的結(jié)果一致,，本研究發(fā)現(xiàn)雌激素聯(lián)合黃體酮會增加乳腺癌的發(fā)病率。雖然在確診為乳腺癌之后,，激素的應(yīng)用并不會影響患者的預(yù)后,，但是由于聯(lián)合激素應(yīng)用增加了患者的發(fā)病率，所以可以預(yù)期的是聯(lián)合激素應(yīng)用組中的死亡率也會相應(yīng)的增加,。(生物谷Bioon.com)
doi: 10.1093/jnci/djt043
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Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study
Rowan T. Chlebowski, JoAnn E. Manson, Garnet L. Anderson, Jane A. Cauley, Aaron K. Aragaki, Marcia L. Stefanick, Dorothy S. Lane, Karen C. Johnson, Jean Wactawski-Wende, Chu Chen, Lihong Qi, Shagufta Yasmeen, Polly A. Newcomb and Ross L. Prentice .
Background In the Women’s Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied.
Methods We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.
Results After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.
Conclusions Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.
