Background: Germline pathogenic variants (PV) inBRCA1andBRCA2genes, which account for 20% of familial breast cancer (BC) cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. Previous studies, mostly including higher numbers ofBRCA1BC patients, yielded conflicting results regardingBRCA1/2BC outcomes. In the Portuguese population,BRCA2BC is diagnosed more frequently thanBRCA1BC. We aimed to compare clinicopathological characteristics and prognosis between BC patients withBRCA1andBRCA2mutations and a control group without germline PV (BRCA-wt). Furthermore, we explored the frequency and outcomes of risk-reducing surgeries inBRCA-mutated patients. Methods: Prospective follow-up was proposed for patients with a diagnosedBRCA1/2PV. For this study, a matched control group (by age at diagnosis, by decade, and by stage at diagnosis) included BC patients without germline PV. We compared overall survival (OS) and invasive disease-free survival (iDFS) within the three groups, and the use of risk-reducing surgeries among theBRCAcohort. Results: For a mean follow-up time of 113.0 months,BRCA-wt patients showed longer time to recurrence (p= 0.002) and longer OS (p< 0.001). Among patients withBRCAmutations, no statistical differences were found, although patients withBRCA2BC had longer iDFS and OS. Uptake of risk-reducing surgeries (contralateral prophylactic mastectomy and salpingo-oophorectomy) were negative predictors of invasive disease and death, respectively. Conclusions: Testing positive for aBRCAPV is associated with a higher risk of relapse and death in patients with BC in the Portuguese population. Risk-reducing mastectomy and salpingo-oophorectomy were associated with lower incidence of relapse and longer median iDFS and OS, respectively.
背景：BRCA1与BRCA2基因的种系致病性变异占家族性乳腺癌病例的20%，具有高外显率，且与遗传性乳腺癌/卵巢癌综合征相关。既往研究（多数纳入较多BRCA1乳腺癌患者）关于BRCA1/2乳腺癌预后的结论存在矛盾。在葡萄牙人群中，BRCA2乳腺癌的诊断频率高于BRCA1乳腺癌。本研究旨在比较携带BRCA1与BRCA2突变乳腺癌患者、以及无种系致病性变异对照组（BRCA-wt）的临床病理特征及预后，并探讨BRCA突变患者接受风险降低手术的频率与结局。 方法：对确诊BRCA1/2致病性变异的患者进行前瞻性随访研究。本研究通过诊断年龄（按十年分段）及诊断分期匹配，纳入无种系致病性变异的乳腺癌患者作为对照组。比较三组患者的总生存期和无浸润性疾病生存期，并分析BRCA突变队列中风险降低手术的实施情况。 结果：在平均113.0个月的随访期内，BRCA-wt患者的复发间隔时间更长（p=0.002），总生存期也更长（p<0.001）。在BRCA突变患者中虽未发现统计学差异，但BRCA2乳腺癌患者表现出更长的无浸润性疾病生存期和总生存期。风险降低手术（对侧预防性乳房切除术与输卵管卵巢切除术）的实施分别与降低浸润性疾病发生风险和死亡风险相关。 结论：在葡萄牙人群中，BRCA致病性变异检测阳性与乳腺癌患者更高的复发风险和死亡风险相关。风险降低性乳房切除术和输卵管卵巢切除术分别与较低的复发发生率、更长的中位无浸润性疾病生存期和总生存期相关。
Comparing Prognosis forBRCA1,BRCA2, and Non-BRCA Breast Cancer
肿瘤(癌症)患者之家