In a prospective cross-sectional study reported in JCO Global Oncology, Gupta et al found that women with ovarian cancer in India had a high prevalence of pathogenic or likely pathogenic BRCA variants.

As stated by the investigators: “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.”

Study Details

The study enrolled 239 women with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer at nine centers across India between March 2018 and December 2018. Patients were enrolled irrespective of family history of breast or ovarian cancer or histology. Testing for germline BRCA1/BRCA2 mutations was performed using a standard next-generation sequencing assay.

Key Findings

Among the 239 women, the median age was 53.0 years (range = 23.0–86.0 years); 203 (84.9%) had newly diagnosed disease; 36 (15.1%) had a family history of ovarian or breast cancer; and 159 (66.5%) had the serous subtype of epithelial ovarian cancer. Overall, 230 patients (96.2%) had ovarian cancer, 8 (3.3%) had primary peritoneal cancer, and 1 (0.4%) had fallopian tube cancer.

Germline pathogenic/likely pathogenic BRCA1 or BRCA2 variants were detected in 51 women (21.3%; 95% confidence interval [CI] = 16.3%–27.1%); BRCA1 variants were found in 37 (15.5%, 95% CI = 11.1%–20.7%) and BRCA2 variants were found in 14 (5.9%, 95% CI = 3.2%–9.6%). No women carried both BRCA1 and BRCA2 variants. Variants of uncertain significance (VUS) were detected in BRCA1 in four women (1.7%, 95% CI = 0.5%–4.2%) and in BRCA2 in six (2.5%, 95% CI = 0.9%–5.4%). Overall, pathogenic/likely pathogenic or VUS mutations were found in 61 women (25.5%).

Among the 61 women with BRCA1/2 pathogenic/likely pathogenic or VUS mutations, 31 (50.8%) had frameshift mutation (51.2% of BRCA1 and 45.0% of BRCA1 variants), 13 (21.3%) had missense mutation (14.6% and 35.0%), 8 (13.1%) had nonsense mutation (12.2% and 15.0%), 4 (6.6%) had splice site mutation (9.8% and 0%), and 5 (8.2%) had other mutations (12.2% and 5.0%).

A higher prevalence of pathogenic/likely pathogenic variants was associated with a family history of breast or ovarian cancer, with such variants observed in 20 (55.6%, 95% CI = 38.1%–72.1%) of 36 patients with vs 41 (20.2%, 95% CI = 14.9%–26.4%) of 203 without a family history (P < .0001).  

A trend toward higher prevalence of pathogenic/likely pathogenic mutations was observed among women with the serous subtype of ovarian cancer, with such variants found in 40 (25.2%, 95% CI = 18.6%–32.6%) of 159 of these women, compared with 11 (13.8%, 95% CI = 7.1%–23.3%) of 80 women with nonserous subtypes (P = .064). Among 34 women with known endometrioid, clear cell, or mucinous histology, 2 of 34 (5.9%, 95% CI = 0.7%–19.7%) had germline BRCA1/2 mutations, including 0 of 15 with clear cell or mucinous histology.

No significant association of pathogenic/likely pathogenic BRCA1/2 mutations with age was observed, with such variants found in 20 (22.2%, 95% CI = 14.1%–32.2%) of 90 women aged ≤ 50 years and in 31 (20.8%, 95% CI = 14.6%–28.2%) of 149 aged > 50 years (P = .796).

No significant association was observed between pathogenic/likely pathogenic variants and number of prior lines of treatment, with such variants found in 36 (19.8%, 95% CI = 14.3%–26.3%) of 182 (76.2% of total population) patients who had received one or no lines of previous treatment vs 15 (26.3%, 95% CI = 15.5%–39.7%) of 57 who had received two or more lines of treatment (P = .293).

The investigators stated: “Our analysis suggests that, although the prevalence of BRCA1/2 mutations was higher in patients with family history of breast and/or ovarian cancer, a considerable minority of patients without such history (20.2%) also harbored the mutations. This suggests that the absence of family history is not adequate as a screening strategy for germline testing. The prevalence of these mutations was higher in patients with serous histology, and no patient with known clear cell or mucinous tumors had a pathogenic mutation, suggesting that histologic subtype may be used to triage patients for testing. Age was not associated with the prevalence of these mutations and should not be incorporated in clinical decision-making to test for germline predisposition.”

They concluded: “There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.”

Sudeep Gupta, MBBS, MD, DM, of Tata Memorial Centre, Tata Memorial Hospital, Mumbai, is the corresponding author of the JCO Global Oncology article.

Disclosure: The study was supported by AstraZeneca Pharma India Ltd. For full disclosures of the study authors, visit ascopubs.org.