Current Perspective| Volume 69, P127-134, December 2016

Current perspectives on recommendations for BRCA genetic testing in ovarian cancer patients

Published:November 04, 2016DOI:


      • Offer BRCA genetic testing to all invasive epithelial OC patients (excluding borderline and mucinous cancers).
      • Testing should be irrespective of age.
      • Ideally offer testing at diagnosis, although patients can be referred at any stage.
      • Retrospective testing should be offered to patients in long-term follow-up.
      • Tumour testing should be considered in non-germline-mutated patients.


      Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2, together with the first poly adenosine diphosphate ribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA-mutated OC, has led to reconsideration of referral criteria for OC patients. Provided here is a review of the existing data and guidelines in the European Union, relating to recommendations, as well as considerations, for the referral of OC patients for BRCA genetic testing. Based on this review of newly updated guidance and up-to-date evidence, the following is recommended: all patients with invasive epithelial OC (excluding borderline or mucinous), including those with fallopian tube and peritoneal cancers, should be considered as candidates for referral for BRCA genetic testing, irrespective of age; genetic testing should ideally be offered at diagnosis, although patients can be referred at any stage; retrospective testing should be offered to patients in long-term follow-up because of the implications for family members and individual future breast cancer risk; and germline BRCA testing of a blood/saliva sample should initially be conducted and, if negative, tumour tissue should be tested (to identify non-germline [somatic] BRCA PARPi therapy candidates).


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ferlay J.
        • Steliarova-Foucher E.
        • Lortet-Tieulent J.
        • Rosso S.
        • Coebergh J.W.
        • Comber H.
        • et al.
        Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012.
        Eur J Cancer. 2013; 49: 1374-1403
        • Zhong Q.
        • Peng H.L.
        • Zhao X.
        • Zhang L.
        • Hwang W.T.
        Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis.
        Clin Cancer Res. 2015; 21: 211-220
        • Shu C.A.
        • Pike M.C.
        • Jotwani A.R.
        • Friebel T.M.
        • Soslow R.A.
        • Levine D.A.
        • et al.
        Uterine Cancer after risk-reducing salpingo-oophorectomy without hysterectomy in women with BRCA mutations.
        JAMA Oncol. 2016 Jun 30; ([Epub ahead of print])
        • Eccles D.M.
        • Balmaña J.
        • Clune J.
        • Ehlken B.
        • Gohlke A.
        • Hirst C.
        • et al.
        Selecting patients with ovarian cancer for germline BRCA mutation testing: findings from guidelines and a systematic literature review.
        Adv Ther. 2016; 33: 129-150
        • Moschetta M.
        • George A.
        • Kaye S.B.
        • Banerjee S.
        BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer.
        Ann Oncol. 2016; 27: 1449-1455
        • Hahnen E.
        • Baumann K.H.
        • Heimbach A.
        • Reuss A.
        • Jackisch C.
        • Hauke J.
        • et al.
        Prevalence of somatic mutations in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1 study).
        J Clin Oncol. 2016; 34 (abstr 5544)
        • Pennington K.P.
        • Walsh T.
        • Harrell M.I.
        • Lee M.K.
        • Pennil C.C.
        • Rendi M.H.
        • et al.
        Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube and peritoneal carcinomas.
        Clin Cancer Res. 2014; 20: 764-775
        • Ledermann J.
        • Harter P.
        • Gourley C.
        • Friedlander M.
        • Vergote I.
        • Rustin G.
        • et al.
        Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in randomised phase 2 trial.
        Lancet Oncol. 2015; 15: 852-861
        • Alsop K.
        • Fereday S.
        • Meldrum C.
        • DeFazio A.
        • Emmanuel C.
        • George J.
        • et al.
        BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.
        J Clin Oncol. 2012; 30: 2654-2663
        • George A.
        • Riddell D.
        • Seal S.
        • Talukdar S.
        • Mahamdallie S.
        • Ruark E.
        • et al.
        Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients.
        Sci Rep. 2016 Jul 13; 6: 29506
        • Balmaña J.
        • Diez O.
        • Rubio I.
        • Castiglione M.
        • on behalf of the ESMO Guidelines Working Group
        BRCA in breast cancer: ESMO clinical practice guidelines.
        Ann Oncol. 2010; 21: v20-v22
        • NCCN
        Genetic/familial high-risk assessment: breast and Ovarian. Version 2., 2015 (Available at:) ([Accessed June 2016])
      1. SGO clinical practice statement: genetic testing for ovarian cancer. 2014 ([Accessed June 2016])
        • Marth C.
        • Hubalek M.
        • Petru E.
        • Polterauer S.
        • Reinthaller A.
        • Schauer C.
        • et al.
        AGO Austria recommendations for genetic testing of patients with ovarian cancer.
        Wien Klin Wochenschr. 2015; 127: 652-654
        • Claes K.
        • Denys H.
        • Huizing M.
        • Vergote I.
        • Kirdelka F.
        • De Greve J.
        • et al.
        Therapy-orienting testing of BRCA1 and BRCA2 germline mutations in women with ovarian cancer.
        Belg J Med Oncol. 2015; 9: 65-70
        • Foretová L.
        • Macháčková E.
        • Palácová M.
        • Navrátilová M.
        • Svoboda M.
        • Petráková K.
        [Recommended extension of indication criteria for genetic testing of BRCA1 and BRCA2 mutations in hereditary breast and ovarian cancer syndrome].
        Klin Onkol. 2016; 29: S9-S13
      2. Care guidelines. Ovarian cancer. 2012 (Available at:)


        • Pinto C.
        • Bella M.A.
        • Capoluongo E.
        • Carrera P.
        • Clemente C.
        • Colombo N.
        • et al.
        Recommendations for the implementation of BRCA testing in the care and treatment pathways of ovarian cancer patients.
        Future Oncol. 2016; 12 ([Epub ahead of print]): 2071-2075

      6. Llort G, Chirivella I.

        • Llort G.
        • Chirivella I.
        • Morales R.
        • Serrano R.
        • Sanchez A.B.
        • Teule A.
        • et al.
        SEOM clinical guidelines in hereditary breast and ovarian cancer.
        Clin Transl Oncol. 2015; 17: 956-961
        • Scottish Intercollegiate Guidelines Network (SIGN)
        Management of epithelial ovarian cancer.
        SIGN, Edinburgh2013 (SIGN publication no. 135). [November 2013]. Available from: URL:
        • NHS England
        Clinical commissioning policy: genetic testing for BRCA1 and BRCA2 mutations.
        2015 (Available at:)
        • Norquist B.M.
        • Harrell M.I.
        • Brady M.F.
        • Walsh T.
        • Lee M.K.
        • Gulsuner S.
        • et al.
        Inherited mutations in women with ovarian carcinoma.
        JAMA Oncol. 2015; ([Epub ahead of print]): 1-9
        • Jacobi C.E.
        • van Ierland Y.
        • van Asperen C.J.
        • Hallensleben E.
        • Devilee P.
        • Jan Fleuren G.
        • et al.
        Prediction of BRCA1/2 mutation status in patients with ovarian cancer from a hospital based cohort.
        Genet Med. 2007; 9: 173-179
        • Malander S.
        • Ridderheim M.
        • Måsbäck A.
        • Loman N.
        • Kristoffersson U.
        • Olsson H.
        • et al.
        One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations: results of a prospective study in Southern Sweden.
        Eur J Cancer. 2004; 40: 422-428
        • Soegaard M.
        • Kjaer S.K.
        • Cox M.
        • Wozniak E.
        • Hogdall C.
        • Blaakaer J.
        • et al.
        BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark.
        Clin Cancer Rev. 2008; 14: 3761-3767
        • Risch H.A.
        • McLaughlin J.R.
        • Cole D.E.
        • Rosen B.
        • Bradley L.
        • Fan I.
        • et al.
        Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario.
        Can J Natl Cancer Inst. 2006; 98: 1694-1706
        • Candido-dos-Reis F.J.
        • Song H.
        • Goode E.L.
        • Cunningham J.M.
        • Fridley B.L.
        • Larson M.C.
        • et al.
        Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer.
        Clin Cancer Res. 2015; 21: 652-657
        • Percival N.
        • George A.
        • Gyertson J.
        • Hamill M.
        • Fernandes A.
        • Davies E.
        • et al.
        The integration of BRCA testing into oncology clinics.
        Br J Nurs. 2016; 25: 690-694
        • Schwartz M.D.
        • Valdimarsottir H.B.
        • Peshkin B.N.
        • Mandelblatt J.
        • Nusbaum R.
        • Huang A.T.
        • et al.
        Randomized noninferiority trial of telephone versus in-person genetic counselling for hereditary breast and ovarian cancer.
        J Clin Oncol. 2014; 32: 18-26
        • Lambrechts S.
        • Smeets D.
        • Moisse M.
        • Braicu E.I.
        • Vanderstichele A.
        • Zhao H.
        • et al.
        Genetic heterogeneity after first-line chemotherapy in high-grade serous ovarian cancer.
        Eur J Cancer. 2016; 53: 51-64
        • Kristeleit R.
        • Swisher E.
        • Oza A.
        • Coleman R.L.
        • Scott C.
        • Konecny G.
        • et al.
        Final results of ARIEL2 (part 1): a phase 2 trial to prospectively identify ovarian cancer (OC) responders to rucaparib using tumor genetic analysis.
        Eur Cancer Congr. 2015; 51: s531