Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial
Abstract
Background Olaparib, a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells. A maximum tolerated dose and initial signal of efficacy in BRCA-deficient ovarian cancers have been reported. We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or BRCA2 mutations and advanced breast cancer.Methods Women (aged >or=18 years) with confirmed BRCA1 or BRCA2 mutations and recurrent, advanced breast cancer were assigned to two sequential cohorts in a phase 2 study undertaken in 16 centres in Australia, Germany, Spain, Sweden, the UK, and the USA. The first cohort (n=27) was given continuous oral olaparib at the maximum tolerated dose (400 mg twice daily), and the second (n=27) was given a lower dose (100 mg twice daily). The primary efficacy endpoint was objective response rate (ORR). This study is registered with ClinicalTrials.gov, number NCT00494234.Findings Patients had been given a median of three previous chemotherapy regimens (range 1-5 in cohort 1, and 2-4 in cohort 2). ORR was 11 (41%) of 27 patients (95% CI 25-59) in the cohort assigned to 400 mg twice daily, and six (22%) of 27 (11-41) in the cohort assigned to 100 mg twice daily. Toxicities were mainly at low grades. The most frequent causally related adverse events in the cohort given 400 mg twice daily were fatigue (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), nausea (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), vomiting (grade 1 or 2, three [11%]; grade 3 or 4, three [11%]), and anaemia (grade 1 or 2, one [4%]; grade 3 or 4, three [11%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, 11 [41%]; none grade 3 or 4) and fatigue (grade 1 or 2, seven [26%]; grade 3 or 4, one [4%]).Interpretation The results of this study provide positive proof of concept for PARP inhibition in BRCA-deficient breast cancers and shows a favourable therapeutic index for a novel targeted treatment strategy in patients with tumours that have genetic loss of function of BRCA1-associated or BRCA2-associated DNA repair. Toxicity in women with BRCA1 and BRCA2 mutations was similar to that reported previously in those without such mutations.Funding AstraZeneca.
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Paribs are generally well tolerated by patients, with few reported side effects.
“Notably, Paribs are in general well tolerated by patients with few reported side effects (Audeh et al., 2010; Bundred et al., 2013; Tutt et al., 2010).”
From Pharmacological Inhibition of poly(ADP-ribose) polymerases improves fitness and mitochondrial function in skeletal muscle (2014) · cites this paper as Tutt et al., 2010
Cites
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660 · see citing works
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683 · see citing works
Self-citationA Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1
Miki, Y., Swensen, J. J., Shattuck-Eidens, D. M., Futreal, P. A., Harshman, K., Tavtigian, S. V., Liu, Q., Cochran, C., Bennett, L. M., Ding, W., et al. (1994) · Science · doi:10.1126/science.7545954 · Cited by 6,069 · see citing works
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198 · see citing works
Identification of the breast cancer susceptibility gene BRCA2
Wooster, R., Bignell, G. R., Lancaster, J., Swift, S., Seal, S., Mangion, J., Collins, N., Gregory, S. G., Gumbs, C. E., Micklem, G., et al. (1995) · Nature · doi:10.1038/378789a0 · Cited by 3,645 · see citing works
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from <i>BRCA</i> Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634 · see citing works
Self-citationBreast cancer and hormone-replacement therapy in the Million Women Study
Beral, V. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14065-2 · Cited by 2,986 · see citing works
Genome-wide association study identifies novel breast cancer susceptibility loci
Easton, D. F., Pooley, K. A., Dunning, A. M., Pharoah, P. D. P., Thompson, D., Ballinger, D. G., Struewing, J. P., Morrison, J., Field, H., Luben, R., et al. (2007) · Nature · doi:10.1038/nature05887 · Cited by 2,319 · see citing works
Self-citationAudeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279 · see citing works
Self-citationSmithson, M. J. (2000) · SAGE Publications Ltd eBooks · doi:10.4135/9781446218525 · Cited by 1,871 · see citing works
The Concept of Synthetic Lethality in the Context of Anticancer Therapy
Kaelin, W. G. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1691 · Cited by 1,369 · see citing works
Brca1 Controls Homology-Directed DNA Repair
Moynahan, M. E., Chiu, J. W., Koller, B. H., & Jasin, M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80202-6 · Cited by 1,245 · see citing works
Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
Sakai, W., Swisher, E. M., Karlan, B. Y., Agarwal, M. K., Higgins, J., Friedman, C., Villegas, E., Jacquemont, C., Farrugia, D. J., Couch, F. J., et al. (2008) · Nature · doi:10.1038/nature06633 · Cited by 1,086 · see citing works
Jonkers, J., Meuwissen, R. L. J., van der Gulden, H. M. L., Peterse, H. L., van der Valk, M., & Berns, A. J. M. (2001) · Nature Genetics · doi:10.1038/ng747 · Cited by 1,053 · see citing works
Resistance to therapy caused by intragenic deletion in BRCA2
Edwards, S. L., Brough, R., Lord, C. J., Natrajan, R., Vatcheva, R., Levine, D. A., Boyd, J., Reis-Filho, J. S., & Ashworth, A. (2008) · Nature · doi:10.1038/nature06548 · Cited by 1,011 · see citing works
Fong, P. C. C., Yap, T. A., Boss, D. S., Carden, C. P., Mergui‐Roelvink, M., Gourley, C., Grève, J. D., Lubiński, J., Shanley, S., Messiou, C., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.26.9589 · Cited by 1,009 · see citing works
Self-citationBRCA2 Is Required for Homology-Directed Repair of Chromosomal Breaks
Moynahan, M. E., Pierce, A. J., & Jasin, M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00174-5 · Cited by 1,007 · see citing works
Lakhani, S., van de Vijver, M., Jacquemier, J., Anderson, T., Osin, P., McGuffog, L., & Easton, D. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.09.023 · Cited by 888 · see citing works
Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
Mendes‐Pereira, A. M., Martin, S. A., Brough, R., McCarthy, A., Taylor, J. R., Kim, J., Waldman, T. A., Lord, C. J., & Ashworth, A. (2009) · EMBO Molecular Medicine · doi:10.1002/emmm.200900041 · Cited by 630 · see citing works
Liu, X., Holstege, H. H., van der Gulden, H. M. L., Treur-Mulder, M., Zevenhoven, J., Velds, A., Kerkhoven, R. M., van Vliet, M. H., Wessels, L. F. A., Peterse, J. L., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702969104 · Cited by 474 · see citing works
Secondary BRCA1 Mutations in BRCA1 -Mutated Ovarian Carcinomas with Platinum Resistance
Swisher, E. M., Sakai, W., Karlan, B. Y., Wurz, K., Urban, N. D., & Taniguchi, T. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0088 · Cited by 457 · see citing works
Tutt, A. N. J., Bertwistle, D., Valentine, J., Gabriel, A., Swift, S., Ross, G., Griffin, C. S., Thacker, J., & Ashworth, A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.17.4704 · Cited by 429 · see citing works
Self-citationPerez, E. A., Lerzo, G. L., Pivot, X. B., Thomas, E. S., Vahdat, L. T., Bosserman, L. D., Viens, P., Cai, C., Mullaney, B. P., Peck, R., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.09.3849 · Cited by 393 · see citing works
Tirkkonen, M., Johannsson, O. T., Agnarsson, B. A., Olsson, H. L., Ingvarsson, S., Karhu, R., Tanner, M., Isola, J. J., Barkardottir, R. B., Borg, Å., et al. (1997) · PubMed · Cited by 354 · see citing works
The relationship between the roles of BRCA genes in DNA repair and cancer predisposition
Tutt, A. N. J., & Ashworth, A. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02434-6 · Cited by 340 · see citing works
Self-citationSakai, W., Swisher, E. M., Jacquemont, C. F., Chandramohan, K. V., Couch, F. J., Langdon, S. P., Wurz, K., Higgins, J., Villegas, E., & Taniguchi, T. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-1178 · Cited by 322 · see citing works
Tutt, A. N. J., Gabriel, A., Bertwistle, D., Connor, F., Paterson, H., Peacock, J., Ross, G., & Ashworth, A. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80479-5 · Cited by 321 · see citing works
Self-citationFumoleau, P., Largillier, R., Clippe, C., Dieras, V. C., Orfeuvre, H., Lesimple, T., Culine, S., Audhuy, B., Serin, D., Curé, H., et al. (2003) · European Journal of Cancer · doi:10.1016/j.ejca.2003.11.007 · Cited by 304 · see citing works
Collins, N., McManus, R., Wooster, R., Mangion, J., Seal, S., Lakhani, S. R., Ormiston, W. J., Daly, P. A., Ford, D., & Easton, D. F. (1995) · PubMed · Cited by 243 · see citing works
Tutt, A. N. J., Lord, C. J., McCabe, N., Farmer, H., Turner, N. C., Martin, N. M. B., Jackson, S. P., Smith, G. C. M., & Ashworth, A. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.012 · Cited by 195 · see citing works
Self-citationVinorelbine (Navelbine) as a salvage treatment for advanced breast cancer
Degardin, M., Bonneterre, J. M., Hecquet, B., et al. (1994) · Annals of Oncology · doi:10.1093/oxfordjournals.annonc.a058873 · Cited by 147 · see citing works
Epidemiology of breast cancer: Findings from the nurses' health study
Colditz, G. A. (1993) · Cancer · doi:10.1002/cncr.2820710413 · Cited by 124 · see citing works
High allele loss rates at I7q I2‐q2I in breast and ovarian tumors from BRCAI‐linked families
Cornelis, R. S., Neuhausen, S. L., Johansson, O., Arason, A., Kelsell, D. P., Ponder, B. A. J., Tonin, P. N., Hamann, U., Lindblom, A., Lalle, P., et al. (1995) · Genes Chromosomes and Cancer · doi:10.1002/gcc.2870130310 · Cited by 119 · see citing works
Kriege, M., Seynaeve, C., Meijers-Heijboer, H. E. J., Collee, M. J., Menke‐Pluymers, M. B. E., Bartels, C. C. M., Tilanus‐Linthorst, M. M. A., Blom, J., Huijskens, E., Jager, A., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.9067 · Cited by 104 · see citing works
Merajver, S. D., Frank, T. S., Xu, J., et al. (1995) · PubMed · Cited by 97 · see citing works
Clinical management of BRCA1 and BRCA2 mutation carriers
Domchek, S. M., & Weber, B. (2006) · Oncogene · doi:10.1038/sj.onc.1209881 · Cited by 77 · see citing works
Self-citationThe pathology of familial breast cancer: Immunohistochemistry and molecular analysis
Osin, P. P., & Lakhani, S. R. (1999) · Breast Cancer Research · doi:10.1186/bcr11 · Cited by 69 · see citing works
Neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients
Gronwald, J., Byrski, T., Huzarski, T., Dent, R. A., Bielicka, V., Zuziak, D., Wiśniowski, R., Lubiński, J., & Narod, S. A. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.502 · Cited by 61 · see citing works
Tutt, A. N. J., van Oostrom, C. T. M., Ross, G. M., STEEG, H. V., & Ashworth, A. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf037 · Cited by 53 · see citing works
Self-citationAbsence or low number of telomere repeats at junctions of dicentric chromosomes
Wan, T. S. K., Martens, U. M., Poon, S. S. S., Tsao, S., Ha, S., & Lansdorp, P. M. (1999) · Genes Chromosomes and Cancer · doi:10.1002/(sici)1098-2264(199901)24:1 · Cited by 45 · see citing works
Cisplatin chemotherapy in the treatment of BRCA1-positive metastatic breast cancer (MBC)
Byrski, T., Foszczynska-Kloda, M., Huzarski, T., Dent, R. A., Gronwald, J., Cybulski, C., Dębniak, T., Górski, B., Lubiński, J., & Narod, S. A. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.15_suppl.1099 · Cited by 14 · see citing works
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Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease
Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.66 · Cited by 3,079 · see citing works
Audeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279 · see citing works
Self-citationAdjuvant Olaparib for Patients with <i>BRCA1</i> - or <i>BRCA2</i> -Mutated Breast Cancer
Tutt, A. N. J., Garber, J. E., Kaufman, B., Viale, G., Fumagalli, D., Rastogi, P., Gelber, R. D., de Azambuja, E., Fielding, A., Balmaña, J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105215 · Cited by 1,729 · see citing works
Self-citationLord, C. J., & Ashworth, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.21 · Cited by 1,257 · see citing works
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
Davies, H., Glodzik, D., Morganella, S., Yates, L. R., Staaf, J., Zou, X., Ramakrishna, M., Martin, S., Boyault, S., Sieuwerts, A. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4292 · Cited by 1,086 · see citing works
Self-citationDNA repair dysregulation from cancer driver to therapeutic target
Curtin, N. J. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3399 · Cited by 1,051 · see citing works
Iniparib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer
O'Shaughnessy, J., Osborne, C., Pippen, J. E., Yoffe, M., Patt, D., Rocha, C., Koo, I. C., Sherman, B. M., & Bradley, C. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1011418 · Cited by 817 · see citing works
A decade of clinical development of PARP inhibitors in perspective
Mateo, J., Lord, C. J., Serra, V., Tutt, A., Balmaña, J., Castroviejo-Bermejo, M., Cruz, C., Oaknin, A., Kaye, S. B., & de Bono, J. S. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz192 · Cited by 743 · see citing works
Self-citationThe effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance
Bouwman, P., & Jonkers, J. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3342 · Cited by 615 · see citing works
Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond
Curtin, N. J., & Szabo, C. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.006 · Cited by 369 · see citing works
Vaidyanathan, A., Sawers, L., Gannon, A.-L., Chakravarty, P., Scott, A. L., Bray, S. E., Ferguson, M. J., & Smith, G. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.203 · Cited by 364 · see citing works
NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease
Cerutti, R., Pirinen, E., Lamperti, C., Marchet, S., Sauve, A. A., Li, W., Leoni, V., Schon, E. A., Dantzer, F., Auwerx, J., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.001 · Cited by 343 · see citing works
Biomarkers for Homologous Recombination Deficiency in Cancer
Hoppe, M. M., Sundar, R., Tan, D. S. P., & Jeyasekharan, A. D. (2018) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djy085 · Cited by 329 · see citing works
Watkins, J. A., Irshad, S., Grigoriadis, A., & Tutt, A. N. (2014) · Breast Cancer Research · doi:10.1186/bcr3670 · Cited by 327 · see citing works
Self-citationBiology and Management of Patients With Triple-Negative Breast Cancer
Sharma, P. (2016) · The Oncologist · doi:10.1634/theoncologist.2016-0067 · Cited by 294 · see citing works
BRCA locus-specific loss of heterozygosity in germline BRCA1 and BRCA2 carriers
Maxwell, K. N., Wubbenhorst, B., Wenz, B. M., De Sloover, D., Pluta, J., Emery, L., Barrett, A., Kraya, A. A., Anastopoulos, I. N., Yu, S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00388-9 · Cited by 296 · see citing works
Self-citationPirinen, E., Cantó, C., Jo, Y. S., Morato, L., Zhang, H., Menzies, K. J., Williams, E. G., Mouchiroud, L., Moullan, N., Hagberg, C., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.04.002 · Cited by 254 · see citing works
“Within the time frameof this study, and in linewith findings inParp-1 / mice (Bai et al., 2011) and in patients treatedwithOlaparib (Audehet al., 2010; Bundred et al., 2013; Tutt et al., 2010), no toxicity or genomic instability was seen in MRL-45696-treated mice.”
BackgroundResultBeyond DNA Repair: Additional Functions of PARP-1 in Cancer
Weaver, A. N., & Yang, E. S. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00290 · Cited by 246 · see citing works
Advances in the treatment of advanced oestrogen-receptor-positive breast cancer
Turner, N. C., Neven, P., Loibl, S., & Andre, F. (2017) · The Lancet · doi:10.1016/s0140-6736(16)32419-9 · Cited by 205 · see citing works
Synthetic lethality of PARP inhibition in cancers lacking<i>BRCA1</i>and<i>BRCA2</i>mutations
Dedes, K. J., Wilkerson, P. M., Wetterskog, D., Weigelt, B., Ashworth, A., & Reis-Filho, J. S. (2011) · Cell Cycle · doi:10.4161/cc.10.8.15273 · Cited by 191 · see citing works
Cisplatin Resistance Associated with PARP Hyperactivation
Michels, J., Vitale, I., Galluzzi, L., Adam, J., Olaussen, K. A., Kepp, O., Senovilla, L., Talhaoui, I., Guegan, J., Enot, D. P., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3000 · Cited by 176 · see citing works
Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment
Gu, G., Dustin, D., & Fuqua, S. A. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.11.005 · Cited by 163 · see citing works
Effect of ASCO/CAP guidelines for determining ER status on molecular subtype
Deyarmin, B., Kane, J. L., Valente, A. L., van Laar, R., Gallagher, C., Shriver, C. D., & Ellsworth, R. E. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2588-8 · Cited by 149 · see citing works
Evans, D. G. R., van Veen, E. M., Byers, H. J., Wallace, A. J., Ellingford, J. M., Beaman, G., Santoyo-Lopez, J., Aitman, T. J., Eccles, D. M., Lalloo, F. I., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2018.07.002 · Cited by 95 · see citing works
Cheng, H., Zhang, Z., Borczuk, A., Powell, C. A., Balajee, A. S., Lieberman, H. B., & Halmos, B. (2013) · Carcinogenesis · doi:10.1093/carcin/bgs393 · Cited by 99 · see citing works
Bundred, N., Gardovskis, J., Jaskiewicz, J., Eglitis, J., Paramonov, V., McCormack, P., Swaisland, H., Cavallin, M., Parry, T., Carmichael, J., et al. (2013) · Investigational New Drugs · doi:10.1007/s10637-012-9922-7 · Cited by 89 · see citing works
Self-citationPrasad, C. B., Prasad, S. B., Yadav, S. S., Pandey, L. K., Singh, S., Pradhan, S., & Narayan, G. (2017) · Scientific Reports · doi:10.1038/s41598-017-13232-3 · Cited by 84 · see citing works
Schoonen, P. M., Kok, Y. P., Wierenga, E., Bakker, B., Foijer, F., Spierings, D. C. J., & van Vugt, M. A. T. M. (2019) · Molecular Oncology · doi:10.1002/1878-0261.12573 · Cited by 81 · see citing works
EMBRACE, Rebbeck, T. R., HEBON, Friebel, T. M., Mitra, N., Wan, F., Chen, S., Andrulis, I. L., Apostolou, P., Arnold, N., et al. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0768-3 · Cited by 71 · see citing works
Self-citationLucas, A. L., Frado, L. E., Hwang, C., Kumar, S., Khanna, L. G., Levinson, E. J., Chabot, J. A., Chung, W. K., & Frucht, H. (2014) · Cancer · doi:10.1002/cncr.28662 · Cited by 68 · see citing works
A Comparative Genomic Approach for Identifying Synthetic Lethal Interactions in Human Cancer
Deshpande, R., Asiedu, M. K., Klebig, M., Sutor, S., Kuzmin, E., Nelson, J., Piotrowski, J., Ho Shin, S., Yoshida, M., Costanzo, M., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3956 · Cited by 64 · see citing works
Lee, J.-M., Peer, C. J., Yu, M., Amable, L., Gordon, N., Annunziata, C. M., Houston, N., Goey, A. K. L., Sissung, T. M., Parker, B., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1546 · Cited by 56 · see citing works
Guestini, F., McNamara, K. M., Ishida, T., & Sasano, H. (2016) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1125469 · Cited by 58 · see citing works
The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer
Abraham, J. E., Pinilla, K., Dayimu, A., Grybowicz, L., Demiris, N., Harvey, C., Drewett, L. M., Lucey, R., Fulton, A., Roberts, A. N., et al. (2024) · Nature · doi:10.1038/s41586-024-07384-2 · Cited by 53 · see citing works
Self-citationUnderstanding Resistance Mechanisms and Expanding the Therapeutic Utility of PARP Inhibitors
Lim, J., & Tan, D. S. P. (2017) · Cancers · doi:10.3390/cancers9080109 · Cited by 52 · see citing works
Upreti, M., Jyoti, A., Johnson, S. E., Swindell, E. P., Napier, D., Sethi, P., Chan, R., Feddock, J. M., Weiss, H. L., O’Halloran, T. V., et al. (2106) · Oncotarget · doi:10.18632/oncotarget.9490 · Cited by 21 · see citing works
Surrogate markers for targeted therapy-based treatment activity and efficacy
Bianchini, G., & Gianni, L. (2011) · JNCI Monographs · doi:10.1093/jncimonographs/lgr024 · Cited by 2 · see citing works
- Authors
- Tutt, A., Robson, M., Garber, J. E., Domchek, S. M., Audeh, M. W., Weitzel, J. N., Friedlander, M., Arun, B., Loman, N., Schmutzler, R. K., Wardley, A., Mitchell, G., Earl, H., Wickens, M., & Carmichael, J.
- Affiliations
- Guy's Hospital (GB)
- Memorial Sloan Kettering Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- Abramson Cancer Center (US)
- Cedars-Sinai Medical Center (US)
- City Of Hope National Medical Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Lund University (SE)
- University of Cologne (DE)
- The Christie Hospital (GB)
- Peter MacCallum Cancer Centre (AU)
- University of Cambridge (GB)
- AstraZeneca (United Kingdom) (GB)
- Corresponding author
- Tutt, Andrew
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 376
- Issue
- 9737
- Pages
- 235-244
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W3093265161
- Cited by
- 1,655
- References
- 41
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 41 · 2023: 51 · 2022: 64 · 2021: 66 · 2020: 106 · 2019: 97 · 2018: 120 · 2017: 150 · 2016: 147 · 2015: 139 · 2014: 133 · 2013: 129 · 2012: 143
- FWCI
- 75.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- AstraZeneca
- Cancer Research Society
- Susan G. Komen
- Topics
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
- Keywords
- olaparib, PARP inhibitors, BRCA1 mutation, BRCA2 mutation, advanced breast cancer, synthetic lethality, objective response rate, dose escalation, adverse events, tolerability, germline mutation carriers, targeted therapy, maximum tolerated dose, anemia, fatigue, nausea and vomiting
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Adult, Aged, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Middle Aged, Phthalazines, Piperazines, Prospective Studies, Germ-Line Mutation, Genes, BRCA1, Maximum Tolerated Dose, Genes, BRCA2
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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