BRCA mutation frequency and clinical features of ovarian cancer patients: A report from a Chinese study group

Abstract

Aim: Subjects with germline BRCA1/2 mutations ( gBRCAm) have an increased risk of developing breast cancer and ovarian cancer. At present, knowledge of BRCA1/2 mutation frequency in Chinese patients with ovarian cancer is still insufficient, and the detailed clinical information of these patients is poorly understood. Methods: A total of 547 unselected ovarian cancer patients were enrolled, and their gBRCAm status was detected. Clinical characteristics including age, personal and family history, histopathologic diagnosis, carbohydrate antigen 125 (CA-125) level, ascites, Federation International of Gynecology and Obstetrics (FIGO) stage, residual lesions, platinum sensitivity, recurrence interval and survival information were collected. Accurate assessments of disease response were based on the RECIST standard or CA-125 level. Results: In 547 patients with ovarian cancer, we detected 129 (23.6%) patients with pathogenic mutations, 84 patients with BRCA1 mutations (15.4%) and 45 patients with BRCA2 mutations (8.2%). Twenty-five novel mutations were identified, and the mutation of BRCA1, c.5470_5477del8, was the most common mutation in this study. BRCA1/2 mutations were significantly associated with age; personal and family history; FIGO stage; secondary recurrence interval; sensitivity to platinum in 1st, 2nd and 3rd line treatment; and response to doxorubicin liposomes. Patients with BRCA1/2 mutations showed significant advantages in 3-and 5-year survival rates but no advantage in long-term survival. Conclusion: BRCA1/2 mutation prevalence in Chinese ovarian cancer patients is higher than the international rate. We recommend BRCA1/2 testing for patients with family histories and personal histories of malignancy and genetic counseling for cancer in healthy people with high-risk family histories.

The Role of Secondary Cytoreductive Surgery in Primary Platinum-sensitive Recurrent HGSOC Patients With Different BRCA1/2 Mutation Status: a Retrospective Study

“…In previous literature reports, the mutation rate of BRCA1/2 in Chinese ovarian cancer patients was between 16.7-28.5% (11,22,23), while in our study, the proportion of patients with BRCA1/2 mutation was as high as 42.0%. In addition, BRCAmut patients have a lower age of onset and a higher proportion of fully sensitive patients (PFI > 12 months).…”

“…Patients with BRCA1/2 mutations usually have longer PFI, and platinum-based chemotherapy after relapse is more effective than patients without BRCA1/2 mutations (10,11). Whether BRCAmut patients will bene t from SCS is controversial.…”

PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance

“…DSBs can only be repaired through homologous recombination (HR) repair or non-homologous end joining (NHEJ). As previously discussed, HR is essential for the error-free repair of DSBs and requires functional BRCA1/2 proteins (Offit, 2006;Palomba et al, 2014;Vos et al, 2018;Bu et al, 2019). In HR deficient tumors, such as BRCA1/2 mutated tumors, the inhibition of PARP yields DSBs which can only be repaired through NHEJ.…”

Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients

“…Interestingly, the top recurrently detected mutations varies between different studies, including the BRCA1:c.1081del, c.964del, c.3770_3771del, c.2371_2372del and c.5470_5477del etc. (12,(19)(20)(21); this is probably caused by the different ethnic origins and geographic locations of the included patients. Several studies have reported the BRCA1:c.5470_5477del as the most frequently detected mutation in Chinese OC patients; of note, the patients enrolled in these studies were mainly from northern China (13,20,22), and studies on the southern Chinese revealed different top mutations (12,19,21).…”

“…( 12 , 19 – 21 ); this is probably caused by the different ethnic origins and geographic locations of the included patients. Several studies have reported the BRCA1 :c.5470_5477del as the most frequently detected mutation in Chinese OC patients; of note, the patients enrolled in these studies were mainly from northern China ( 13 , 20 , 22 ), and studies on the southern Chinese revealed different top mutations ( 12 , 19 , 21 ). In this study, almost all the patients are from Henan, the central region of China and the origin of Chinese civilization.…”