PARP Inhibitors in BRCA Gene-Mutated Ovarian Cancer and Beyond

Banerjee, Susana; Kaye, Stan B.

doi:10.1007/s11912-011-0193-9

Cited by 42 publications

(43 citation statements)

References 41 publications

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“…This approach has been investigated using poly(ADP)ribose polymerase (PARP) inhibitors in BRCA gene‐mutated ovarian and breast cancers [20], [21]. A phase II study with the PARP inhibitor olaparib did not demonstrate activity in advanced CRC patients with MSS or MSI‐high tumors [22].…”

Section: Molecular Tumor Boardmentioning

confidence: 99%

DNA Polymerase ε Deficiency Leading to an Ultramutator Phenotype: A Novel Clinically Relevant Entity

Castellucci

Goldstein

et al. 2017

The Oncologist

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Two cases of metastatic colorectal cancer with a POLE mutation, both of which were ultramutated and microsatellite stable, are presented and discussed from the standpoint of the basic biochemical mechanisms leading to a unique phenotype in POLE deficiency, the challenges faced with interpreting the genomic profiling of tumors in this important subset of patients, and the potential clinical implications.

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Section: Molecular Tumor Boardmentioning

confidence: 99%

DNA Polymerase ε Deficiency Leading to an Ultramutator Phenotype: A Novel Clinically Relevant Entity

Castellucci

Goldstein

et al. 2017

The Oncologist

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“…[1][2][3][4][5][6] For the patient with ovarian cancer, BRCA mutation status has prognostic and therapeutic implications. [7][8][9][10][11] In addition, BRCA1/BRCA2 genetic testing of patients with ovarian cancer with suggestive personal and/or family histories, followed by predictive genetic testing of family members, is a cost-effective strategy to prevent future breast and ovarian cancers. 12 The likelihood of identifying a BRCA1/BRCA2 mutation is increased in patients with ovarian cancer who have a family history of breast and/or ovarian cancer and in patients who are of Ashkenazi Jewish ancestry.…”

Section: Introductionmentioning

confidence: 99%

Underestimation of Risk of a BRCA1 or BRCA2 Mutation in Women With High-Grade Serous Ovarian Cancer by BRCAPRO: A Multi-Institution Study

Daniels

Babb

King

et al. 2014

JCO

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A B S T R A C T PurposeIdentification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer. MethodsBRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy. ResultsOne hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P Ͻ .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P Ͻ .001), underestimation increased as age at diagnosis decreased (P ϭ .02), and model performance varied by institution (P ϭ .02). ConclusionPatients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history.

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“…Pharmacological inhibition of poly-ADP-ribose polymerase induces cell death in tumors with mutations in certain DNA repair pathways, when combined with DNA damaging chemotherapies. Then, poly-ADP-ribose polymerase inhibitors have been investigated for the treatment of patients with BRCA 1 mutation, as a strategy to potentiate the DNA damaging effects of chemotherapy and irradiation [26,27].…”

Section: Function and Involvement Of Brca1 In Dna Repair Pathwaymentioning

confidence: 99%