Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

Abstract

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

Next-generation sequencing based detection of BRCA1 and BRCA2 large genomic rearrangements in Chinese cancer patients

“…In this study, the frequency of co-occurring variants in both the BRCA1 and BRCA2 genes in the pan-cancer cohort was approximately 3%, which was somehow higher than that of most previous studies ( 22 – 25 ). The possible reason for the relatively high frequency in our study might be the fact that except for pathogenic variants, we also included likely-pathogenic variants and LGRs, which were not included in some studies.…”

Comprehensive Germline Genomic Profiling of Patients with Ovarian Cancer: A Cross-Sectional Study

“…However, Gupta et al, in a prospective study ( n = 239) of unselected patients of carcinoma ovary from all across India, reported BRCA mutations in 25.5% of patients, which may be closer to true prevalence in the population. 13…”

Universal Germline Genetic Testing in Epithelial Ovarian Cancer: Promises and challenges

“…This study provides the much-required detailed information of the prevalence in unselected Indian ovarian cancer patient population (15.5%) while also providing estimates for various enriched subgroups of patients who are ≤ 50 years (22.2%), serous epithelial ovarian cancers (25.2%), or those with a family history of cancer (55.6%). 11 The results show that the prevalence of germline mutations is much higher than most solid tumors. Contrary to expectations, subgroups such as non-serous (13.8%), older than 50 years (20.8%), or those without a family history (20.2%) also had a clinically relevant prevalence of germline mutation.…”

“…Contrary to expectations, subgroups such as non-serous (13.8%), older than 50 years (20.8%), or those without a family history (20.2%) also had a clinically relevant prevalence of germline mutation. 11 This implies that several patients will be unable to qualify for the genetic test if any selection criteria are used. Identifying the maximum number of index EOC cases will not only help to personalize their therapy, provide cancer surveillance, and ensure future cancer prevention but also extend the benefit of identifying family members who have inherited the mutation and through culturally sensitive and evidence-based genetic counseling, testing, and risk management approaches.…”

“…In addition to the BRCA1/2 genes, mutations in other genes associated with the development of ovarian cancer such as PALB2 , PRIB1 , the core RAD genes, CHEK2 among others were not reported even though a 94 gene NGS panel was used. 2 7 11 Moreover, copy number variation or large genomic rearrangement were not reported, which potentially lead to underestimation of the prevalence.…”