BRCA1 and implications for response to chemotherapy in ovarian cancer

Quinn, Jennifer E.; Carser, Judith; James, Colin R.; Kennedy, Richard D.; Harkin, D. Paul

doi:10.1016/j.ygyno.2008.12.015

Cited by 73 publications

(61 citation statements)

References 91 publications

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“…24 Furthermore, it has been reported that BRCA mutation carriers are highly sensitive to platinum-based chemotherapy, which leads to improved survival for BRCA-associated OC patients compared with those who have sporadic OC. 29,30 However, despite the improved outcome in patients with BRCA-associated OC, the 5-year and 10-year survival rates remain poor (63% and 35%, respectively), 31 which has to be taken into account at counseling. Therefore, precise data concerning the risks of PBC or CBC after BRCA-associated OC are warranted to enable optimization of and more patient-tailored counseling regarding the subsequent strategies for this patient subgroup.…”

Section: Introductionmentioning

confidence: 99%

The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers

Vencken¹,

Kriege²,

Hooning³

et al. 2012

Cancer

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BACKGROUND:The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC). METHODS: From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n ¼ 79) or with a history of unilateral BC (at risk of CBC; n ¼ 37) were selected. The control groups consisted of unaffected BRCA mutation carriers (n ¼ 351) or mutation carriers who had a previous unilateral BC (n ¼ 294), respectively. The risks of PBC and CBC were calculated using the Kaplan-Meier survival method with death considered as a competing risk event. RESULTS: Women with BRCA-associated OC had lower 2-year, 5-year, and 10-year risks of PBC (3%, 6%, and 11%, respectively) compared with unaffected mutation carriers (6%, 16%, and 28%, respectively; P ¼ .03), although they had a considerably higher mortality rate at similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%, respectively; P < .001). In BRCA mutation carriers with a previous unilateral BC, the 2-year, 5-year, and 10-year risks of CBC were nonsignificantly lower in patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%, 16%, and 34%, respectively; P ¼ .06), whereas the mortality rate was higher in patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%, respectively; P < .001). CONCLUSIONS: Patients with BRCA-associated OC had a lower risk of developing a subsequent PBC or CBC than mutation carriers without OC, whereas the risk of dying from OC was greater than the risk of developing BC. These data may facilitate more tailored counseling for this patient subgroup, although confirmative studies are warranted. Cancer 2013;119:955-62. V C 2012 American Cancer Society.KEYWORDS: BRCA, ovarian cancer, primary breast cancer, contralateral breast cancer, risk-reducing mastectomy. INTRODUCTIONWomen who have a germline mutation in the breast cancer susceptibility genes BRCA1 or BRCA2 have substantially elevated risks of developing both breast cancer (BC) and ovarian cancer (OC). It has been estimated that the cumulative 10-year risk of primary BC (PBC) ranges between 6% and 23% for BRCA1/BRCA2 mutation carriers, and the highest risk is observed between ages 40 and 50 years.1-6 After unilateral BC, the estimated 10-year risk of contralateral BC (CBC) is 29% to 39% for patients with BRCA1-associated BC and 23% to 35% for patients with BRCA2-associated BC. 1,[7][8][9][10] Factors that potentially affect the latter include age at first BC diagnosis (especially when diagnosed at ages <50 years),

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Section: Introductionmentioning

confidence: 99%

The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers

Vencken¹,

Kriege²,

Hooning³

et al. 2012

Cancer

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“…Furthermore, antisense or siRNA-based inhibition of endogenous BRCA1 expression promoted the increased sensitivity to cisplatin that was associated with the decreased DNA repair by NER and an increased apoptosis (Lafarge et al, 2001;Quinn et al, 2003). This indicates that the reduced BRCA1 expression observed in sporadic cancers may also be exploited for DNA damage-based chemotherapy Quinn et al, 2009). In a similar situation, BRCA1-deficient mouse embryonic stem cells displayed defective DNA repair and a 100-fold increased sensitivity to the alkylating agent mitomycin C and cisplatin than those containing wild-type BRCA1 (Bhattacharyya et al, 2000;Moynahan et al, 2001).…”

Section: Cisplatin-protein Adductsmentioning

confidence: 99%

“…Likewise, the nucleocapsid Zn 2+ finger NCp7 protein, a protein required for the recognition and packaging of viral RNA, became attached to some platinum compounds, when its ability to bind nucleic acid was changed and prevented viral infectivity (de Paula et al, 2009;Musah, 2004 In recent years, there has been significant progress made in evaluating what happens when BRCA1 is inactivated so it cannot respond to DNA damage in cancer cells, in other words, taking advantage of the inherent weakness of the BRCA1 dysfunction in cancer cells. These cells have increased sensitivity to DNA-damaging agents that eventually result in major genomic instability and cell death (Amir et al, 2010;Ashworth, 2008;Helleday et al, 2008;Lieberman, 2008;Powell & Bindra, 2009;Quinn et al, 2009;Tassone et al, 2009;Zhu et al, 2009). Cancerous cells with inactivated BRCA1 had defects in DNA repair of double strand breaks (DSBs) (Farmer et al, 2005;Kennedy et al, 2004;Litman et al, 2008).…”

Section: Cisplatin-protein Adductsmentioning

confidence: 99%

“…The DNA repair activity of the cell is an important determinant of a cells sensitivity to chemotherapeutic agents. It is known that resistance to DNA-damaging agents can be associated with increased cellular repair activities, while defects in DNA repair pathways result in hypersensitivity to damage (Kelley & Fishel, 2008;Quinn et al, 2003Quinn et al, , 2009. Several studies have clearly demonstrated that the impairment or absence of genes or proteins responsible for DNA damage repair, frequently causes genomic instability, cell cycle arrest and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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A DNA Repair Protein BRCA1 as a Potentially Molecular Target for the Anticancer Platinum Drug Cisplatin

Ratanaphan¹

2011

DNA Repair

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“…This was reversed by imatinib treatment, resulting in 12 BRCA1 upregulation. In ovarian cancer it was suggested that BRCA1 can act as a predictive marker of response to chemotherapy (Quinn et al, 2009) and dysfunctional BRCA1 resulted in resistance to taxanes and other chemotherapeutics. On the other hand, reconstitution of BRCA1 into ovarian cancer cells, carrying BRCA1 mutation, reversed the resistance and sensitized cells to paclitaxel (Zhou et al, 2003).…”

Section: Brca1 In the Regulation Of The Mitotic Checkpointmentioning

confidence: 99%

BCR-ABL Hits at Mitosis; Implications for Chromosomal Instability, Aneuploidy and Therapeutic Strategy

Piwocka¹,

Wolanin²,

Kusio-Kobiałka³

et al. 2011

Myeloid Leukemia - Basic Mechanisms of Leukemogenesis

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BRCA1 and implications for response to chemotherapy in ovarian cancer

Cited by 73 publications

References 91 publications

The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers

The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers

A DNA Repair Protein BRCA1 as a Potentially Molecular Target for the Anticancer Platinum Drug Cisplatin

BCR-ABL Hits at Mitosis; Implications for Chromosomal Instability, Aneuploidy and Therapeutic Strategy

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