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Review
. 2018 Dec 11;10(12):506.
doi: 10.3390/cancers10120506.

Targeting BRCA Deficiency in Breast Cancer: What are the Clinical Evidences and the Next Perspectives?

Emanuel Nicolas  1 , François Bertucci  2   3 , Renaud Sabatier  4   5 , Anthony Gonçalves  6   7
Affiliations
Review

Targeting BRCA Deficiency in Breast Cancer: What are the Clinical Evidences and the Next Perspectives?

Emanuel Nicolas et al. Cancers (Basel). .

Abstract

Breast cancers (BC) associated with germline mutations of BRCA1/2 represent 3⁻5% of cases. BRCA1/2-associated BC have biological features leading to genomic instability and potential sensitivity to DNA damaging agents, including poly(ADP-ribose) polymerase (PARP) and platinum agents. In this review, we will summarize clinical trials of chemotherapy and PARP inhibitors (PARPi), alone or in combination, at the early or late stage of BRCA1/2-associated BC. We will also present the mechanisms of resistance to PARPi as well as the new therapeutic strategies of association with PARPi. Finally, we will discuss under which conditions the use of DNA damaging agents can be extended to the BRCA1/2-wild type population, the BRCAness concept.

Keywords: BRCA; DNA-damaging agents; platinum; poly(ADP)-ribose polymerase.

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Conflict of interest statement

E.N. declares no conflict of interest. A.G. declares travel accomodation and meeting registration fees (Roche, Novartis, Amgen, Pfizer, Lilly, Astra Zeneca, Cellgene, Boheringer). F.B. declares no conflict of interest. R.S. received research grants and non-financial support from Astra Zeneca, is consultant for Pfizer and Roche, and received non-financial support from Pfizer, Roche, and BMS.

Figures

Figure 1
Figure 1
Synthetic lethality: Synthetic lethality occurs when the simultaneous mutation of two genes is lethal for the cell, while mutation in each individual gene is not.
See this image and copyright information in PMC

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References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries: Global Cancer Statistics 2018. CA Cancer J. Clin. 2018 doi: 10.3322/caac.21492. - DOI - PubMed
    1. Antoniou A., Pharoah P.D., Narod S., Risch H.A., Eyfjord J.E., Hopper J.L., Loman N., Olsson H., Johannsson O., Borg A., et al. Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies. Am. J. Hum. Genet. 2003;72:1117–1130. doi: 10.1086/375033. - DOI - PMC - PubMed
    1. King M.-C. Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2. Science. 2003;302:643–646. doi: 10.1126/science.1088759. - DOI - PubMed
    1. Peto J., Collins N., Barfoot R., Seal S., Warren W., Rahman N., Easton D.F., Evans C., Deacon J., Stratton M.R. Prevalence of BRCA1 and BRCA2 Gene Mutations in Patients with Early-Onset Breast Cancer. JNCI J. Natl. Cancer Inst. 1999;91:943–949. doi: 10.1093/jnci/91.11.943. - DOI - PubMed
    1. Copson E.R., Maishman T.C., Tapper W.J., Cutress R.I., Greville-Heygate S., Altman D.G., Eccles B., Gerty S., Durcan L.T., Jones L., et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): A prospective cohort study. Lancet Oncol. 2018;19:169–180. doi: 10.1016/S1470-2045(17)30891-4. - DOI - PMC - PubMed

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