Introduction/Background Incidence of Ovarian Cancer (OC) in Portsmouth is approximately 110 cases per year, standing as the 10th largest city in the UK. Individuals with germline BRCA1/2 (gBRCA1/2) alterations treated with the PARP inhibitors (PARPi) tend to respond better than patients with wild-type BRCA1/2. Additionally, somatic BRCA1/2 (sBRCA1/2) alterations induce the sensitivity to PARPi.
The aim of the study was to investigate the rate of concordance of gBRCA1/2 with sBRCA1/2 pathogenic mutations to increase screening uptake for prescription of the newly NICE approved PARPi tablets available for gBRCA and sBRCA mutation carriers.
Methodology 70 patients diagnosed with ovarian cancer were screened: 50 with High Grade Serous Carcinoma (HGSC), 2 Low Grade Serous Carcinoma (LGSC), 4 Clear Cell Carcinoma (CCC), 2 Carcinosarcoma, 11 Endometrioid Adenocarcinoma (EdAd) and 1 mucinous carcinoma. Patients were tested for BCRA1/2 germline mutations upfront, followed by testing of tumour specimens for somatic mutations using NGS.
Results 9 cases had gBRCA1/2 pathogenic mutations: 5 HGSC had gBRCA1, 3 HGSC and 1 EdAd had gBRCA2. 7 cases had sBRCA1/2 mutations: 4 gBRCA1 and 3 gBRCA2 HGSC had sBRCA1 and sBRCA2 respectively. EdAd gBRCA2 had no somatic mutations; 1 HGSC patient with gBRCA1 had no sBRCA1/2 mutations.
1 HGSC wild-type gBRCA showed pathogenic sBRCA1 frameshift mutation. 2 EdAd and 1 CCC wild-type gBRCA showed sBRCA1/2 mutations of unknown clinical significance. LGSC, carcinosaromas and mucinous carcinoma were wild-type gBRCA with no somatic mutations detected.
Conclusion Detection of both germline and somatic BRCA1/2 mutations is required for effective PARPi treatment. Somatic tests should be offered to increase the number of patients suitable for targeted therapy. The consistency of gBRCA1/2 uptake (13%) was in keeping with published data, whereas the sBRCA1/2 uptake was 11.4%, which is less than the expected 15%. More research into cases with sBRCA1/2 mutations of unknown clinical significance is warranted.
Disclosure Nothing to disclose.
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