Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, Denmark.
Acta Oncol. 2020 Jan;59(1):60-65. doi: 10.1080/0284186X.2019.1648860. Epub 2019 Aug 5.
Preoperative genetic testing affects the surgical decision-making among women with breast cancer. To avoid breast-conserving surgery and to offer the possibility of mastectomy with immediate reconstruction in high-risk patients, genetic testing for pathogenic variants in or and a pedigree-based familial breast cancer risk assessment was offered to younger women with breast cancer in Denmark. We evaluated the impact of the risk stratification through genetic counseling on the uptake of contralateral prophylactic mastectomy (CPM). The prospective cohort study included all women with unilateral breast cancer before the age of 45 who participated in a genetic counseling program during their primary diagnostics in the Central Denmark Region (2013-2018). Each patient was followed from the time of the genetic test result to the end of follow-up to estimate the long-term uptake of CPM as a competing risk-adjusted cumulative incidence. We compared the uptake of CPM between the various genetic risk categories, ages of onset, and family histories in a multivariable Cox proportional hazards regression model, reporting hazard ratios (HR) with two-sided 95% confidence intervals (CIs). 156 females, aged 21-44, learned their genetic test result within a median of 92 days [interquartile range (IQR): 75-114]. The maximal follow-up was 3.8 years (median 1.8; IQR: 0.49-2.5), after which 33% (95% CI: 24-42%) of the patients had undergone CPM. The uptake of CPM was inversely associated with the age of onset (HR 0.92; 95% CI: 0.86-0.98) and significantly higher among BRCA carriers (HR 2.9; 95% CI: 1.3-6.8) and patients from the high risk of breast cancer families (HR 5.6; 95% CI: 1.9-16) compared to the lower genetic risk categories. The risk stratification obtained through genetic counseling had a considerable impact on the surgical decision-making among younger women with breast cancer at long-term follow-up.
术前基因检测会影响乳腺癌女性的手术决策。为避免保乳手术，并为高风险患者提供即刻重建的乳房切除术选择，丹麦为年轻乳腺癌患者提供了针对 或 种致病性变异的基因检测，以及基于家族史的乳腺癌风险评估。我们评估了通过遗传咨询进行风险分层对接受对侧预防性乳房切除术（CPM）的影响。这项前瞻性队列研究纳入了在丹麦中部地区（2013-2018 年）初次诊断期间参加遗传咨询计划的所有 45 岁以下单侧乳腺癌女性。每位患者从基因检测结果的时间开始随访至随访结束，以估计 CPM 的长期接受率，作为竞争风险调整的累积发生率。我们在多变量 Cox 比例风险回归模型中比较了不同遗传风险类别、发病年龄和家族史之间 CPM 的接受率，报告了双侧 95%置信区间（CI）的风险比（HR）。156 名年龄在 21-44 岁的女性在中位数为 92 天[四分位距（IQR）：75-114]内得知了基因检测结果。最大随访时间为 3.8 年（中位数 1.8；IQR：0.49-2.5），在此之后，33%（95%CI：24-42%）的患者接受了 CPM。CPM 的接受率与发病年龄呈负相关（HR 0.92；95%CI：0.86-0.98），BRCA 携带者（HR 2.9；95%CI：1.3-6.8）和来自高乳腺癌风险家族的患者（HR 5.6；95%CI：1.9-16）明显高于低遗传风险类别。遗传咨询获得的风险分层对长期随访的年轻乳腺癌女性的手术决策产生了重大影响。
