Shi Tingyan, Wang Pan, Tang Wenbin, Jiang Rong, Yin Sheng, Shi Di, Wang Qing, Wei Qingyi, Zang Rongyu
Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Zhongshan hospital, Fudan University, Shanghai, China.
Centre Léon Bérard, Laboratoire de la génétique constitutionnelle HCL-CLB, Plateforme de génomique des cancers, Lyon, France.
Cell Physiol Biochem. 2018;47(5):2088-2096. doi: 10.1159/000491477. Epub 2018 Jul 5.
BACKGROUND/AIMS: Prognostic value of germline BRCA1 or BRCA2 (gBRCA1/2) mutations in epithelial ovarian cancer (EOC) remains controversial, especially in the estimation of long-term survival. We previously reported the largest study of gBRCA1/2 mutation prevalence in Chinese EOC patients. The aim of this study is to further illustrate the correlation of residual disease and survival in BRCA-associated EOC in China.
In the current cohort consisting of 615 cases from the Chinese EOC genome-wide association study, we evaluated the association between gBRCA1/2 mutation and clinical outcomes.
Overall, we did not find any significant difference between gBRCA1/2 mutation carriers and non-carriers in both progression-free survival (PFS) and overall survival (OS) (19.3 vs. 18.1 months and 77.2 vs. 73.2 months, P=0.528 and 0.147, HR 0.93 and 0.79, 95%CI 0.74-1.17 and 0.57-1.09, respectively). However, within three years after diagnosis, mutation carriers showed a longer OS than non-carriers (P=0.018, HR 0.53, 95%CI 0.31-0.90). Such a survival advantage decreased along with the extension of follow-up time. Quite interestingly, in the subgroup of patients with gross residual disease, mutation carriers had a longer survival than non-carriers (18.5 vs. 15.1 months and 68.5 vs. 54.3 months, P=0.046 and 0.038, HR 0.74 and 0.65, 95% CI 0.55-1.00 and 0.43-0.98, for PFS and OS respectively).
Our findings provided the evidence that gBRCA1/2 mutation was not associated with survival in Chinese EOC patients, which possibly attributed to more than 37% of the patients without gross residual disease. Survival benefit of gBRCA1/2 mutation was prominent in ovarian cancer patients with gross residual disease.
背景/目的：胚系BRCA1或BRCA2（gBRCA1/2）突变在上皮性卵巢癌（EOC）中的预后价值仍存在争议，尤其是在长期生存的评估方面。我们之前报道了中国EOC患者中关于gBRCA1/2突变患病率的最大规模研究。本研究的目的是进一步阐明中国BRCA相关EOC中残留病灶与生存的相关性。
在当前由来自中国EOC全基因组关联研究的615例病例组成的队列中，我们评估了gBRCA1/2突变与临床结局之间的关联。
总体而言，我们发现gBRCA1/2突变携带者与非携带者在无进展生存期（PFS）和总生存期（OS）方面均无显著差异（分别为19.3个月对18.1个月以及77.2个月对73.2个月，P = 0.528和0.147，风险比[HR]分别为0.93和0.79，95%置信区间[CI]分别为0.74 - 1.17和0.57 - 1.09）。然而，在诊断后的三年内，突变携带者的OS比非携带者更长（P = 0.018，HR 0.53，95%CI 0.31 - 0.90）。这种生存优势随着随访时间的延长而降低。非常有趣的是，在有肉眼可见残留病灶的患者亚组中，突变携带者的生存期比非携带者更长（PFS分别为18.5个月对15.1个月，OS分别为68.5个月对54.3个月，P = 0.046和0.038，HR分别为0.74和0.65，95%CI分别为0.55 - 1.00和0.43 - 0.98）。
我们的研究结果表明，gBRCA1/2突变与中国EOC患者的生存无关，这可能归因于超过37%的患者无肉眼可见残留病灶。gBRCA1/2突变在有肉眼可见残留病灶的卵巢癌患者中的生存获益显著。
