Pierce Lori J, Levin Albert M, Rebbeck Timothy R, Ben-David Merav A, Friedman Eitan, Solin Lawrence J, Harris Eleanor E, Gaffney David K, Haffty Bruce G, Dawson Laura A, Narod Steven A, Olivotto Ivo A, Eisen Andrea, Whelan Timothy J, Olopade Olufunmilayo I, Isaacs Claudine, Merajver Sofia D, Wong Julia S, Garber Judy E, Weber Barbara L
Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI 48109-0010, USA.
J Clin Oncol. 2006 Jun 1;24(16):2437-43. doi: 10.1200/JCO.2005.02.7888. Epub 2006 Apr 24.
We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls.
A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls.
There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05).
IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.
我们比较了携带BRCA1/2基因突变的乳腺癌患者保乳手术及放疗的结果与配对的散发性乳腺癌对照患者的结果。
共有160例携带BRCA1/2基因突变的乳腺癌患者与445例散发性乳腺癌对照患者进行配对。主要终点为乳腺内肿瘤复发（IBTR）率和对侧乳腺癌（CBC）发生率。突变携带者的中位随访时间为7.9年，对照患者为6.7年。
携带者和对照患者的总体IBTR无显著差异；携带者10年和15年的估计复发率分别为12%和24%，对照患者分别为9%和17%（风险比[HR]，1.37；P = 0.19）。对IBTR的多因素分析发现，当将接受过卵巢切除术的携带者排除在分析之外时，BRCA1/2突变状态是IBTR的独立预测因素（HR，1.99；P = 0.04）；接受过卵巢切除术的携带者的IBTR发生率与散发性对照患者无显著差异（P = 0.37）。携带者的CBC明显高于对照患者，携带者10年和15年的估计发生率分别为26%和39%，对照患者分别为3%和7%（HR，10.43；P < 0.0001）。使用他莫昔芬可显著降低突变携带者发生CBC的风险（HR，0.31；P = 0.05）。
接受保乳手术并进行卵巢切除术的BRCA1/2携带者10年的IBTR风险与散发性对照患者相似。正如预期的那样携带者的CBC显著增加。虽然接受他莫昔芬治疗的突变携带者的CBC发生率显著降低，但该发生率仍显著高于对照患者。需要其他策略来降低这些高危女性的对侧乳腺癌发生率。
