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Review
. 2022 Sep 5;14(17):4332.
doi: 10.3390/cancers14174332.

PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond

Maria Clara Saad Menezes  1 , Farah Raheem  2 , Lida Mina  2 , Brenda Ernst  2 , Felipe Batalini  2
Affiliations
Review

PARP Inhibitors for Breast Cancer: Germline BRCA1/2 and Beyond

Maria Clara Saad Menezes et al. Cancers (Basel). .

Abstract

Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors (PARPi) are approved for BRCA1/2 carriers with HER2-negative breast cancer in the adjuvant setting with a high risk of recurrence as well as the metastatic setting. However, the indications for PARPi are broader for patients with other cancer types (e.g., prostate and ovarian cancer), involving additional biomarkers (e.g., ATM, PALB2, and CHEK) and genomic instability scores. Herein, we summarize the data on PARPi and breast cancer and discuss their use beyond BRCA carriers.

Keywords: BRCA1; BRCA2; HRD; PALB2; PARPi; breast cancer; homologous recombination repair.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A synthetic lethality therapeutic approach: poly(ADP) ribose polymerase inhibitors (PARPi) for the treatment of cancers with a deficient homologous recombination repair (HRR) pathway. Neither PARPi nor HRR deficiency (HRD) alone is lethal, but the inadequate repair of double-strand breaks found in HRR-deficient cells renders them sensitive to PARP inhibition.
Figure 2
Figure 2
Search strategy. On 29 April 2022, the following PubMed search was performed: “breast” AND “Olaparib OR AZD2281 OR Talazoparib OR BMN673”. The references were also scanned for eligible studies. There were 177 results. Among them, 106 studies were excluded, as 91 cited the word breast in the body of the text but were not about breast cancer, 6 were not experimental studies, five were subanalyses of included studies, 3 were duplicated studies, and 1 was an experiment that included neither olaparib nor talazoparib. Accordingly, 71 studies were included, with two additional studies from the references.
See this image and copyright information in PMC

References

    1. 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. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–921. doi: 10.1038/nature03445. - DOI - PubMed
    1. Bryant H.E., Schultz N., Thomas H.D., Parker K.M., Flower D., Lopez E., Kyle S., Meuth M., Curtin N.J., Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–917. doi: 10.1038/nature03443. - DOI - PubMed
    1. 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. 2008;26:3785–3790. doi: 10.1200/JCO.2008.16.0812. - DOI - PubMed
    1. Murai J., Huang S.-Y.N., Das B.B., Renaud A., Zhang Y., Doroshow J.H., Ji J., Takeda S., Pommier Y. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012;72:5588–5599. doi: 10.1158/0008-5472.CAN-12-2753. - DOI - PMC - PubMed
    1. The Cancer Genome Atlas Network Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70. doi: 10.1038/nature11412. - DOI - PMC - PubMed

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