Rhiem Kerstin, Engel Christoph, Graeser Monika, Zachariae Silke, Kast Karin, Kiechle Marion, Ditsch Nina, Janni Wolfgang, Mundhenke Christoph, Golatta Michael, Varga Dominic, Preisler-Adams Sabine, Heinrich Tilman, Bick Ulrich, Gadzicki Dorothea, Briest Susanne, Meindl Alfons, Schmutzler Rita K
Breast Cancer Res. 2012 Dec 7;14(6):R156. doi: 10.1186/bcr3369.
While it has been reported that the risk of contralateral breast cancer in patients from BRCA1 or BRCA2 positive families is elevated, little is known about contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations.
A retrospective, multicenter cohort study was performed from 1996 to 2011 and comprised 6,235 women with unilateral breast cancer from 6,230 high risk families that had tested positive for BRCA1 (n = 1,154) or BRCA2 (n = 575) mutations or tested negative (n = 4,501). Cumulative contralateral breast cancer risks were calculated using the Kaplan-Meier product-limit method and were compared between groups using the log-rank test. Cox regression analysis was applied to assess the impact of the age at first breast cancer and the familial history stratified by mutation status.
The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 44.1% (95%CI, 37.6% to 50.6%) for patients from BRCA1 positive families, 33.5% (95%CI, 22.4% to 44.7%) for patients from BRCA2 positive families and 17.2% (95%CI, 14.5% to 19.9%) for patients from families that tested negative for BRCA1/2 mutations. Younger age at first breast cancer was associated with a higher risk of contralateral breast cancer. For women who had their first breast cancer before the age of 40 years, the cumulative risk of contralateral breast cancer after 25 years was 55.1% for BRCA1, 38.4% for BRCA2, and 28.4% for patients from BRCA1/2 negative families. If the first breast cancer was diagnosed at the age of 50 or later, 25-year cumulative risks were 21.6% for BRCA1, 15.5% for BRCA2, and 12.9% for BRCA1/2 negative families.
Contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations is similar to the risk in patients with sporadic breast cancer. Thus, the mutation status should guide decision making for contralateral mastectomy.
虽然已有报道称，来自BRCA1或BRCA2阳性家族的患者发生对侧乳腺癌的风险有所升高，但对于BRCA1/2突变检测呈阴性的高危家族患者的对侧乳腺癌风险，人们了解甚少。
1996年至2011年进行了一项回顾性多中心队列研究，纳入了来自6230个高危家族的6235例单侧乳腺癌女性患者，这些家族BRCA1（n = 1154）或BRCA2（n = 575）突变检测呈阳性或呈阴性（n = 4501）。采用Kaplan-Meier乘积限界法计算对侧乳腺癌累积风险，并使用对数秩检验对组间风险进行比较。应用Cox回归分析评估首次患乳腺癌时的年龄以及按突变状态分层的家族史的影响。
首次患乳腺癌25年后，BRCA1阳性家族患者发生对侧乳腺癌的累积风险为44.1%（95%CI为37.6%至50.6%），BRCA2阳性家族患者为33.5%（95%CI为22.4%至44.7%）,BRCA1/2突变检测呈阴性家族患者为17.2%（95%CI为14.5%至19.9%）.首次患乳腺癌时年龄较小与对侧乳腺癌风险较高相关.对于首次患乳腺癌年龄在40岁之前的女性,25年后BRCA1患者对侧乳腺癌累积风险为55.1%,BRCA2患者为38.4%,BRCA1/2阴性家族患者为28.4%.如果首次乳腺癌在50岁及以后被诊断,25年累积风险BRCA1患者为21.6%,BRCA2患者为15.5%,BRCA1/2阴性家族患者为12.9%.
BRCA1/2突变检测呈阴性的高危家族患者发生对侧乳腺癌的风险与散发性乳腺癌患者相似.因此,突变状态应指导对侧乳房切除术的决策.
