Gronwald Jacek, Robidoux Andre, Kim-Sing Charmaine, Tung Nadine, Lynch Henry T, Foulkes William D, Manoukian Siranoush, Ainsworth Peter, Neuhausen Susan L, Demsky Rochelle, Eisen Andrea, Singer Christian F, Saal Howard, Senter Leigha, Eng Charis, Weitzel Jeffrey, Moller Pal, Gilchrist Dawna M, Olopade Olufunmilayo, Ginsburg Ophira, Sun Ping, Huzarski Tomasz, Lubinski Jan, Narod Steven A
Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Breast Cancer Res Treat. 2014 Jul;146(2):421-7. doi: 10.1007/s10549-014-3026-3. Epub 2014 Jun 21.
Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80 %. Tamoxifen treatment of the first cancer has been associated with a reduction in the risk of a subsequent contralateral cancer. We studied 1,504 women with a known BRCA1 or BRCA2 mutation, 411 women with bilateral breast cancer (cases) and 1,093 women with unilateral breast cancer (controls) in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of first breast cancer as the cases. For each woman who used tamoxifen, the starting and stopping dates were abstracted and the duration of tamoxifen use was calculated. Three hundred and thirty-one women had used tamoxifen (22 %); of these 84 (25 %) had completed four or more years of tamoxifen, the remainder stopped prematurely or were current users. For women with up to 1 year of tamoxifen use, the odds ratio for contralateral breast cancer was 0.37 (95 % CI 0.20-0.69; p = 0.001) compared to women with no tamoxifen use. Among women with 1-4 years of tamoxifen use the odds ratio was 0.53 (95 % CI 0.32-0.87; p = 0.01). Among women with four or more years of tamoxifen use the odds ratio was 0.83 (95 % CI 0.44-1.55; p = 0.55). Short-term use of tamoxifen for chemoprevention in BRCA1 and BRCA2 mutation carriers may be as effective as a conventional 5-year course of treatment.
携带BRCA1或BRCA2基因突变的女性一生中患乳腺癌的风险约为80%。他莫昔芬治疗首例癌症与降低随后对侧癌症的风险有关。在一项匹配病例对照研究中,我们研究了1504名已知携带BRCA1或BRCA2基因突变的女性,其中411名患有双侧乳腺癌(病例组),1093名患有单侧乳腺癌(对照组)。对照女性的年龄与病例组相似,首次诊断乳腺癌的年龄也相似。对于每一位使用他莫昔芬的女性,提取其开始和停止日期,并计算他莫昔芬的使用时长。331名女性使用过他莫昔芬(22%);其中84名(25%)完成了四年或更长时间的他莫昔芬治疗,其余女性过早停药或仍在使用。与未使用他莫昔芬的女性相比,使用他莫昔芬时长至多1年的女性,对侧乳腺癌的比值比为0.37(95%可信区间0.20 - 0.69;p = 0.001)。在使用他莫昔芬1 - 4年的女性中,比值比为0.53(95%可信区间0.32 - 0.87;p = 0.01)。在使用他莫昔芬四年或更长时间的女性中,比值比为0.83(95%可信区间0.44 - 1.55;p = 0.55)。在BRCA1和BRCA2基因突变携带者中,短期使用他莫昔芬进行化学预防可能与传统的5年疗程治疗效果相同。