Key Points
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Poly [ADP-ribose] polymerase (PARP) inhibitors are an effective maintenance therapy in patients with platinum-sensitive ovarian cancer and also in those who have received multiple lines of previous treatment
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BRCA-mutation status provides important information for the identification of patients that are most likely to benefit from treatment with PARP inhibitors
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BRCA-mutation testing should be offered to patients with ovarian cancer on the basis of histological subtype, and should not be limited to those with a family and/or personal history of BRCA-related malignancy
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Additional tests to identify patients that would benefit from PARP inhibitors, including the use of homologous recombination deficiency (HRD) gene signatures and assessing genomic loss of heterozygosity seem promising
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Data from ongoing clinical trials will help define how best to select patients with ovarian cancer for treatment with PARP inhibitors
Abstract
The treatment of patients with ovarian cancer is rapidly changing following the success of poly [ADP-ribose] polymerase (PARP) inhibitors in clinical trials. Olaparib is the first PARP inhibitor to be approved by the EMA and FDA for BRCA-mutated ovarian cancer. Germ line BRCA mutation status is now established as a predictive biomarker of potential benefit from treatment with a PARP inhibitor; therefore, knowledge of the BRCA status of an individual patient with ovarian cancer is essential, in order to guide treatment decisions. BRCA testing was previously offered only to women with a family or personal history of breast and/or ovarian cancer; however, almost 20% of women with high-grade serous ovarian cancer are now recognized to harbour a germ line BRCA mutation, and of these, >40% might not have a family history of cancer and would not have received BRCA testing. A strategy to enable more widespread implementation of BRCA testing in routine care is, therefore, necessary. In this Review, we summarize data from key clinical trials of PARP inhibitors and discuss how to integrate these agents into the current treatment landscape of ovarian cancer. The validity of germ line BRCA testing and other promising biomarkers of homologous-recombination deficiency will also be discussed.
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References
Banerjee, S. & Kaye, S. B. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin. Cancer Res. 19, 961–968 (2013).
Ledermann, J. et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N. Engl. J. Med. 366, 1382–1392 (2012).
Fong, P. C. et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 361, 123–134 (2009).
Fong, P. C. et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J. Clin. Oncol. 28, 2512–2519 (2010).
Kristeleit, R. 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. European Cancer Congress Abstract 2700 (2015).
Ledermann, J. et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 15, 852–861 (2014).
The European Medicines Agency. ema.europa.eu http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003726/human_med_001831.jsp&mid=WC0b01ac058001d124 (2014).
The US department of Health and Human Services. fda.gov http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427554.htm (2014).
Gibson, B. A. & Kraus, W. L. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat. Rev. Mol. Cell Biol. 13, 411–424 (2012).
Krishnakumar, R. & Kraus, W. L. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol. Cell 39, 8–24 (2010).
Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H. & Poirier, G. G. PARP inhibition: PARP1 and beyond. Nat. Rev. Cancer 10, 293–301 (2010).
Bai, P. & Canto, C. The role of PARP-1 and PARP-2 enzymes in metabolic regulation and disease. Cell Metab. 16, 290–295 (2012).
Luo, X. & Kraus, W. L. On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev. 26, 417–432 (2012).
Quenet, D., El Ramy, R., Schreiber, V. & Dantzer, F. The role of poly(ADP-ribosyl)ation in epigenetic events. Int. J. Biochem. Cell Biol. 41, 60–65 (2009).
Scott, C. L., Swisher, E. M. & Kaufmann, S. H. Poly (ADP-ribose) polymerase inhibitors: recent advances and future development. J. Clin. Oncol. 33, 1397–1406 (2015).
Ashworth, A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J. Clin. Oncol. 26, 3785–3790 (2008).
Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).
Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917 (2005).
Konstantinopoulos, P. A., Ceccaldi, R., Shapiro, G. I., D'Andrea, A. D. Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov. 5, 1137–1154 (2015).
Banerjee, S., Kaye, S. B. & Ashworth, A. Making the best of PARP inhibitors in ovarian cancer. Nat. Rev. Clin. Oncol. 7, 508–519 (2010).
Murai, J. et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 72, 5588–5599 (2012).
Patel, A. G., Sarkaria, J. N. & Kaufmann, S. H. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc. Natl. Acad. Sci. USA. 108, 3406–3411 (2011).
O'Connor, M. J. Targeting the DNA damage response in cancer. Mol. Cell 60, 547–560 (2015).
Audeh, M. W. et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 376, 245–251 (2010).
Gelmon, K. A. et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 12, 852–861 (2011).
Oza, A. M. et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 16, 87–97 (2015).
Coleman, R. L. et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation – an NRG oncology/gynecologic oncology group study. Gynecol. Oncol. 137, 386–391 (2015).
Kummar, S. et al. Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer. Clin. Cancer Res. 21, 1574–1582 (2015).
Kaye, S. B. et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J. Clin. Oncol. 30, 372–379 (2012).
Hennessy, B. T. et al. Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer. J. Clin. Oncol. 28, 3570–3576 (2010).
Press, J. Z. et al. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities. BMC Cancer 8, 17 (2008).
Baldwin, R. L. et al. BRCA1 promoter region hypermethylation in ovarian carcinoma: a population-based study. Cancer Res. 60, 5329–5333 (2000).
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011).
Ledermann, J. A. H. et al. Overall survival (OS) in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC) receiving olaparib maintenance monotherapy: an interim analysis. J. Clin. Oncol. 34, (Suppl. Abstr. 5501) (2016).
Matulonis, U. A. et al. Olaparib maintenance therapy in patients with platinum-sensitive, relapsed serous ovarian cancer and a BRCA mutation: overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy. Cancer 122, 1844–1852 (2016).
Astrazeneca media centre. Astrazeneca.com [online] https://www.astrazeneca.com/media-centre/press-releases/2016/lynparza-phase-iii-solo-2-trial-shows-significant-progression-free-survival-benefit-261020161.html (2016).
Domchek, S. M. et al. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol. Oncol. 140, 199–203 (2016).
Kaufman, B. et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J. Clin. Oncol. 33, 244–250 (2015).
Coleman, R. L. et al. Refinement of prespecified cutoff for genomic loss of heterozygosity (LOH) in ARIEL2 part 1: A phase II study of rucaparib in patients (pts) with high grade ovarian carcinoma (HGOC). J. Clin. Oncol. 34, (Suppl. Abstr. 5540) (2016).
Mirza, M. R. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1611310 (2016).
Rubin, S. C. et al. BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Am. J. Obstetr. Gynaecol. 178, 670–677 (1998).
Risch, H. A. et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am. J. Hum. Genet. 68, 700–710 (2001).
Soegaard, M. et al. BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark. Clin. Cancer Res. 14, 3761–3767 (2008).
Satagopan, J. M. et al. Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin. Cancer Res. 8, 3776–3781 (2002).
Moslehi, R. et al. BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am. J. Hum. Genet. 66, 1259–1272 (2000).
Alsop, K. 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. 30, 2654–2663 (2012).
Moller, P. et al. Genetic epidemiology of BRCA mutations—family history detects less than 50% of the mutation carriers. Eur. J. Cancer 43, 1713–1717 (2007).
George, A. S. et al. Implementation of routine BRCA testing of ovarian cancer (OC) patients at the Royal Marsden Hospital. Ann. Oncol. 25 (Suppl 4), iv307 (2014).
Pennington, K. P. 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. 20, 764–775 (2014).
Yang, D. et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 306, 1557–1565 (2011).
Bolton, K. L. et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA 307, 382–390 (2012).
Liu, J. et al. Clinical characteristics and outcomes of BRCA-associated ovarian cancer: genotype and survival. Cancer Genet. 205, 34–41 (2012).
Chetrit, A. et al. Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the National Israeli Study of Ovarian Cancer. J. Clin. Oncol. 26, 20–25 (2008).
Candido-dos-Reis, F. J. et al. Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer. Clin. Cancer Res. 21, 652–657 (2015).
Norquist, B. M. et al. Characteristics of women with ovarian carcinoma who have BRCA1 and BRCA2 mutations not identified by clinical testing. Gynecol. Oncol. 128, 483–487 (2013).
Norquist, B. M. et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2, 1–9 (2015).
Gourley, C. et al. Increased incidence of visceral metastases in Scottish patients with BRCA1/2- defective ovarian cancer: an extension of the ovarian BRCAness phenotype. J. Clin. Oncol. 28, 2505–2511 (2010).
Tan, D. S. P. et al. “BRCAness” syndrome in ovarian cancer: a case-control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J. Clin. Oncol. 26, 5530–5536 (2008).
Adams, S. F. et al. A high response rate to liposomal doxorubicin is seen among women with BRCA mutations treated for recurrent epithelial ovarian cancer. Gynecol. Oncol. 123, 486–491 (2011).
Lorusso, D., Ferrandina, G. & Pignata, S. Phase II prospective study on trabectedin (T) in BRCA-mutated and BRCAness phenotype advanced ovarian cancer (AOC) patients (pts): the MITO 15 trial. J. Clin. Oncol. 32, Abstract 5530 (2014).
Eccles, D. M. et al. Selecting patients with ovarian cancer for germline BRCA mutation testing: findings from guidelines and a systematic literature review. Adv. Ther. 33, 129–150 (2016).
Antoniou, A. C. et al. Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics. J. Med. Genet. 45, 425–431 (2008).
Fischer, C. et al. Evaluating the performance of the breast cancer genetic risk models BOADICEA, IBIS, BRCAPRO and Claus for predicting BRCA1/2 mutation carrier probabilities: a study based on 7352 families from the German Hereditary Breast and Ovarian Cancer Consortium. J. Med. Genet. 50, 360–367 (2013).
Lee, A. J. et al. BOADICEA breast cancer risk prediction model: updates to cancer incidences, tumour pathology and web interface. Br. J. Cancer 110, 535–545 (2014).
Evans, D. G. et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO. J. Med. Genet. 41, 474–480 (2004).
Zhang, S. et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol. Oncol. 121, 353–357 (2011).
George, A. et al. Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients. Sci. Rep. 6, 29506 (2016).
Demsky, R. et al. Keeping it simple: genetics referrals for all invasive serous ovarian cancers. Gynecol. Oncol. 130, 329–333 (2013).
The National Comprehensive Cancer Network, nccn.org https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#ovarian (2015).
Meyer, L. A. et al. Evaluating women with ovarian cancer for BRCA1 and BRCA2 mutations: missed opportunities. Obstet. Gynecol. 115, 945–952 (2010).
Lanceley, A. et al. Family history and women with ovarian cancer: is it asked and does it matter?: an observational study. Int. J. Gynecol. Cancer 22, 254–259 (2012).
Metcalfe, K. A. et al. Uptake of clinical genetic testing for ovarian cancer in Ontario: a population-based study. Gynecol. Oncol. 112, 68–72 (2009).
Balmana, J. et al. BRCA in breast cancer: ESMO clinical practice guidelines. Ann. Oncol. 21 (Suppl. 5), v20–v22 (2010).
Society of Gynecologic Oncology. SGO Clinical Practice Statement: Genetic Testing for Ovarian Cancer. [online] https://www.sgo.org/clinical-practice/guidelines/genetic-testing-for-ovarian-cancer/ (2014).
Marth, C. et al. AGO Austria recommendations for genetic testing of patients with ovarian cancer. Wien. Klin. Wochenschr. 127, 652–654 (2015).
Llort, G. et al. SEOM clinical guidelines in hereditary breast and ovarian cancer. Clin. Transl. Oncol. 17, 956–961 (2015).
Foretova, L. et al. [Recommended extension of indication criteria for genetic testing of BRCA1 and BRCA2 mutations in hereditary breast and ovarian cancer syndrome]. Klin. Onkol. 29 (Suppl. 1), S9–13 (in Czech) (2016).
National Collaborating Centre for Cancer (UK). Familial breast cancer: classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer. NICE Clinical Guidelines 164 (2013).
George, A. UK BRCA mutation testing in patients with ovarian cancer. Br. J. Cancer 113 (Suppl. 1), S17–S21 (2015).
Percival, N. et al. The integration of BRCA testing into oncology clinics. Br. J. Nurs. 25, 690–694 (2016).
Tischkowitz, M. D. et al. The Genetic Testing in Epithelial Ovarian Cancer (GTEOC) Study: direct access to BRCA1/2 genetic testing in oncology. Presented at the 64th Annual Meeting of The American Society of Human Genetics (ASHG) [abst. 3503S]. (2014).
Tischkowitz, M. Working together in the genomics era – lessons from the GTEOC study. Presented at the NCRI Cancer Conference (2015)
Plaskocinska, I. et al. New paradigms for BRCA1/BRCA2 testing in women with ovarian cancer: results of the Genetic Testing in Epithelial Ovarian Cancer (GTEOC) study. J. Med. Genet. 53, 655–661 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02406235 (2015).
Coulet, F. et al. Germline RAD51C mutations in ovarian cancer susceptibility. Clin. Genet. 83, 332–336 (2013).
Rafnar, T. et al. Mutations in BRIP1 confer high risk of ovarian cancer. Nat. Genet. 43, 1104–1107 (2011).
Loveday, C. et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat. Genet. 43, 879–884 (2011).
Loveday, C. et al. Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat. Genet. 44, 475–476; author reply 476 (2012).
Ramus, S. J. et al. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Hum. Mut. 33, 690–702 (2012).
McNeish, I. et al. Preliminary results of ARIEL2, a phase 2 open-label study to identify ovarian cancer patients likely to respond to rucaparib. Ann. Oncol. 25 (Suppl. 4), iv305–iv326 (2014).
National Collaborating Centre for Cancer (UK). National Institute for Health and Clinical Excellence: Guidance. Familial breast cancer: classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer. (2013).
Slade, I. et al. A cost analysis of a cancer genetic service model in the UK. J. Community Genet. 44, 185–194 (2016).
Gadzicki, D. et al. Genetic testing for familial/hereditary breast cancer-comparison of guidelines and recommendations from the UK, France, the Netherlands and Germany. J. Community Genet. 2, 53–69 (2011).
Matulonis, U. A. et al. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann. Oncol. 27, 1013–1019 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01844986 (2016).
Sonnenblick, A. et al. An update on PARP inhibitors—moving to the adjuvant setting. Nat. Rev. Clin. Oncol. 12, 27–41 (2015).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01874353 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01968213 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01847274 (2016).
Wilcoxen, K. M. et al. Use of homologous recombination deficiency (HRD) score to enrich for niraparib sensitive high grade ovarian tumors. J. Clin. Oncol. 33, Abstract 5532 (2015).
Rebbeck, T. R. et al. Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2. Am. J. Hum. Genet. 59, 547–553 (1996).
Peng, G. et al. Genome-wide transcriptome profiling of homologous recombination DNA repair. Nat. Commun. 5, 3361 (2014).
Fojo, T. & Bates, S. Mechanisms of resistance to PARP inhibitors—three and counting. Cancer Discov. 3, 20–23 (2013).
Jaspers, J. E. et al. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov. 3, 68–81 (2013).
Ceccaldi, R. et al. A unique subset of epithelial ovarian cancers with platinum sensitivity and PARP inhibitor resistance. Cancer Res. 75, 628–634 (2015).
Johnson, N. et al. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. Proc. Natl. Acad. Sci. USA. 110, 17041–17046 (2013).
Edwards, S. L. et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 451, 1111–1115 (2008).
Barber, L. J. et al. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. J. Pathol. 229, 422–429 (2013).
Ang, J. E. et al. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin. Cancer Res. 19, 5485–5493 (2013).
Liu, J. F. et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 15, 1207–1214 (2014).
Du, Y. et al. Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors. Nat. Med. 22, 194–201 (2016).
Johnson, N. et al. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nat. Med. 17, 875–882 (2011).
Yalon, M. et al. Overcoming resistance of cancer cells to PARP-1 inhibitors with three different drug combinations. PLoS ONE 11, e0155711 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02477644 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02282020 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02502266 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02446600 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02655016 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02470585 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02723864 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01623349 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02338622 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02734004 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02681237 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02576444 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02208375 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02484404 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02657889 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02354131 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02571725 (2016).
US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01434316 (2016).
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We would like to thank the Royal Marsden Hospital and Institute of Cancer Research National Institute for Health Research (NIHR) Biomedical Research Centre for Cancer (BRC).
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A.G. and S.B. researched data for this article, all authors made a substantial contribution to discussions of content, A.G. and S.B. wrote the manuscript, and all authors reviewed and/or edited the manuscript prior to submission.
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A.G. declares that she has received honoraria from AstraZeneca. S.K. is on the advisory boards of AstraZeneca and Tesaro. S.B. is on the advisory boards of Astrazeneca and Clovis, but declares that she has received no personal financial remuneration as a result of these activities.
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George, A., Kaye, S. & Banerjee, S. Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer. Nat Rev Clin Oncol 14, 284–296 (2017). https://doi.org/10.1038/nrclinonc.2016.191
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DOI: https://doi.org/10.1038/nrclinonc.2016.191
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