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Abstract：
Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC).
We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival.
Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37).
Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors.
We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival.
Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37).
Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors.
摘要：
在患有上皮性卵巢癌（EOC）的女性中，很少报道BRCA1和BRCA2基因中致病性变异的携带者为双突变（BRCA1/2DM）。
我们回顾了英文文献，并询问了三个报告携带BRCA1/2DM的EOC患者的资料库。将36例携带种系BRCA1/2DM的EOC患者的临床病理参数与COEUR队列中具有已知种系BRCA1/BRCA2突变携带者状态的高级别浆液性EOC女性进行了比较（n=376例非携带者，n=65BRCA1和n=38BRCA2)。评估的临床病理参数是诊断时的年龄，疾病阶段，杂合性丢失，突变类型,免疫组织化学谱，进展发生和生存。
BRCA1/2DM患者诊断年龄中位数为51.9岁，类似于BRCA1突变携带者(49.7年，p=.58），并且比BRCA2突变携带者年轻（58.1岁，p=.02）。大多数患者被诊断为晚期（III-IV;82％），并且是创始人/频繁突变的携带者（69％）。组织免疫染色显示无孕激素受体表达和低上皮内炎症。5年生存率(60%)明显低于BRCA2突变携带者(76%,p=.03），但不是BRCA1突变携带者（51%，p=.37）。
我们的数据表明两种突变都有一定的共显性效应，但这些患者的预后与BRCA1突变携带者的预后因素更为相似。
我们回顾了英文文献，并询问了三个报告携带BRCA1/2DM的EOC患者的资料库。将36例携带种系BRCA1/2DM的EOC患者的临床病理参数与COEUR队列中具有已知种系BRCA1/BRCA2突变携带者状态的高级别浆液性EOC女性进行了比较（n=376例非携带者，n=65BRCA1和n=38BRCA2)。评估的临床病理参数是诊断时的年龄，疾病阶段，杂合性丢失，突变类型,免疫组织化学谱，进展发生和生存。
BRCA1/2DM患者诊断年龄中位数为51.9岁，类似于BRCA1突变携带者(49.7年，p=.58），并且比BRCA2突变携带者年轻（58.1岁，p=.02）。大多数患者被诊断为晚期（III-IV;82％），并且是创始人/频繁突变的携带者（69％）。组织免疫染色显示无孕激素受体表达和低上皮内炎症。5年生存率(60%)明显低于BRCA2突变携带者(76%,p=.03），但不是BRCA1突变携带者（51%，p=.37）。
我们的数据表明两种突变都有一定的共显性效应，但这些患者的预后与BRCA1突变携带者的预后因素更为相似。
