From the Peter MacCallum Cancer Centre, St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, and Breast Cancer Trials Australia and New Zealand, University of Newcastle, Newcastle, NSW (P.A.F.), and the University of Sydney, Sydney (A.S.C.) - all in Australia; the Institute of Oncology of Southern Switzerland, Ospedale San Giovanni, Bellinzona (O.P.), Breast Cancer St. Gallen, St. Gallen (T.R.), and the International Breast Cancer Study Group Coordinating Center (R.M., M.R.-P., B.R., A.S.C.), University Hospital Inselspital (M.R.-P.), Bern - all in Switzerland; the University of Chicago Medical Center, Chicago (G.F.F.); the University of Calgary, Calgary, AB, Canada (B.A.W.); the Division of Medical Senology, European Institute of Oncology (M.C.), and the European Institute of Oncology and International Breast Cancer Study Group (A.G.), Milan, Ospedale Papa Giovanni XXIII, Bergamo (C.T.), Azienda Socio Sanitaria Territoriale Sette Laghi-Ospedale di Circolo and Fondazione Macchi, Varese (G.P.), Medical Oncology and Cancer Prevention, IRCCS, National Cancer Institute, Aviano (F.P., S.S.), the Department of Medicine, School of Medical Oncology, University of Udine, Udine (F.P.), Salvatore Maugeri Foundation, Pavia (L.P.), and the Hospital of Prato-Azienda Unità Sanitaria Locale Toscana Centro, Prato (A.D.L.) - all in Italy; the National Institute of Oncology, Budapest, Hungary (I.L.); Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru (H.L.G.); University Hospital 12 de Octubre, Madrid (E.C.), Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital, Barcelona (M.B.), and Instituto Valenciano de Oncologia, Valencia (M.A.C.) - all in Spain; the Susan F. Smith Center for Women's Cancers (H.J.B., E.P.W.) and the International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology (R.D.G., M.M.R.), Dana-Farber Cancer Institute, Harvard Medical School, the Harvard T.H. Chan School of Public Health, and Frontier Science and Technology Research Foundation (R.D.G.) - all in Boston; Institut Bergonié Comprehensive Cancer Center, Université de Bordeaux, Bordeaux, France (H.R.B., M.D.); the Angeles Clinic and Research Institute, Santa Monica, CA (S.M.); Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond (C.E.G.); Mayo Clinic, Rochester, MN (M.P.G., J.N.I.); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore (V.S.); Fred Hutchinson Cancer Research Center, University of Washington, Seattle (N.E.D.); Weston Park Hospital, Sheffield, United Kingdom (R.C.); and the Department of Obstetrics and Gynecology, University Medical Center, Regensburg, Germany (S.B.).
N Engl J Med. 2018 Jul 12;379(2):122-137. doi: 10.1056/NEJMoa1803164. Epub 2018 Jun 4.
In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials.
Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy.
In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group.
Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).
在抑制卵巢功能试验（SOFT）和他莫昔芬和依西美坦试验（TEXT）中，接受芳香化酶抑制剂依西美坦联合卵巢抑制的绝经前妇女的乳腺癌复发率在 5 年内显著低于接受他莫昔芬联合卵巢抑制的妇女。与单独使用他莫昔芬相比，卵巢抑制联合他莫昔芬并不能显著降低复发率。在这里，我们报告了这两项试验的最新结果。
绝经前妇女被随机分配接受 5 年的他莫昔芬、他莫昔芬联合卵巢抑制或依西美坦联合卵巢抑制的 SOFT 治疗，以及接受他莫昔芬联合卵巢抑制或依西美坦联合卵巢抑制的 TEXT 治疗。随机化根据接受化疗进行分层。
在 SOFT 中，单独使用他莫昔芬的无病生存率为 78.9%，他莫昔芬联合卵巢抑制为 83.2%，依西美坦联合卵巢抑制为 85.9%（单独使用他莫昔芬与他莫昔芬联合卵巢抑制相比，P=0.009）。单独使用他莫昔芬的总生存率为 91.5%，他莫昔芬联合卵巢抑制为 93.3%，依西美坦联合卵巢抑制为 92.1%（单独使用他莫昔芬与他莫昔芬联合卵巢抑制相比，P=0.01）；在化疗后仍处于绝经前的妇女中，这一比例分别为 85.1%、89.4%和 87.2%。在接受化疗且 HER2 阴性的妇女中，依西美坦联合卵巢抑制的 8 年远处复发率低于他莫昔芬联合卵巢抑制（SOFT 中低 7.0 个百分点，TEXT 中低 5.0 个百分点）。单独使用他莫昔芬组、他莫昔芬卵巢抑制组和依西美坦卵巢抑制组报告的 3 级或更高级别的不良事件分别为 24.6%、31.0%和 32.3%。
在患有乳腺癌的绝经前妇女中，与单独使用他莫昔芬相比，卵巢抑制联合他莫昔芬可显著提高 8 年无病生存率和总生存率。依西美坦联合卵巢抑制可进一步提高无复发率。接受卵巢抑制的两组不良事件的发生率高于单独使用他莫昔芬组。（由辉瑞等资助；SOFT 和 TEXT 的临床试验.gov 编号分别为 NCT00066690 和 NCT00066703）。
