Basu N N, Ingham S, Hodson J, Lalloo F, Bulman M, Howell A, Evans D G
Department of Breast Surgery, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
Genesis Breast Cancer Prevention Centre, University Hospital of South Manchester NHS Trust, Wythenshawe, Manchester, M23 9LT, UK.
Fam Cancer. 2015 Dec;14(4):531-8. doi: 10.1007/s10689-015-9825-9.
BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2-3% per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.
BRCA1和BRCA2基因的突变携带者在患原发性乳腺癌后，对侧乳腺癌的发病风险会增加。在评估对侧乳腺癌的风险因素后，会讨论降低风险的策略。我们评估了可能在临床实践中有用的潜在风险因素，包括单核苷酸多态性（SNP）检测的新用途。对506名诊断为乳腺癌的BRCA1基因和505名诊断为乳腺癌的BRCA2基因的突变携带者进行了长达30年的观察。对侧乳腺癌的发病风险约为每年2%-3%，至少20年保持不变。这在BRCA1基因和BRCA2基因的携带者中情况相似。40岁前患原发性乳腺癌是一个重要的风险因素，在BRCA1基因携带者中更为明显。由于存在偏差，降低风险的卵巢切除术对降低对侧乳腺癌风险的作用可能被高估了。总体乳腺癌风险SNP评分与对侧乳腺癌的发生之间未发现显著关联。年轻的突变携带者，尤其是那些携带BRCA1基因突变且患乳腺癌的人，发生对侧乳腺癌的风险显著更高，且在20多年里保持不变。对于这组人群，应考虑进行对侧预防性乳房切除术，特别是因为这有生存获益。在为考虑降低风险的卵巢切除术的女性提供咨询时应谨慎，因为在考虑统计偏差后，发现相关的风险降低并不显著，而且可能比之前报道的要小。在评估对侧乳腺癌风险时，SNP检测并未提供任何进一步的鉴别信息。
