BRCA1/2 mutations and expression: Response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer

Dann, Rebecca; DeLoia, Julie A.; Timms, Kirsten M.; Zorn, Kristin K.; Potter, Jennifer; Flake, Darl D.; Lanchbury, Jerry S.; Krivak, Thomas C.

doi:10.1016/j.ygyno.2012.03.006

Cited by 110 publications

(90 citation statements)

References 31 publications

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“…In our population, a significant increase in PFS was registered in BRCA2 carriers compared to BRCA1 carriers and a nonsignificant trend in OS advantage was detected in the same mutated population. This may be partly due to the increased platinum sensitivity of our BRCA2 population: in fact, according to previous reports [43], our data seem to suggest that BRCA2 mutation carriers presented more frequently with platinum-sensitive ovarian cancer than BRCA1 -mutated patients (85.72 vs. 59.67%, respectively; p = 0.009) The comparable rate of optimal surgical cytoreduction reported in our study between the 2 groups (39.5 vs. 50% in BRCA1 and BRCA2 carriers, respectively) seems to imply that neither BRCA status nor the type of mutation are significant predictors of residual tumor volume, and that the improved survival seen in BRCA2 -mutated patients may most likely be related to different chemotherapy susceptibility than to differences in surgical outcome.…”

Section: Discussionmentioning

confidence: 72%

“…To date, this paper represents the most convincing clinical evidence showing that patients with BRCA -related EOC have a better clinical outcome than those with sporadic disease, and that this is due, in part, to the better initial and retained sensitivity to platinum-based chemotherapy of this population [42,43]. In our population, a significant increase in PFS was registered in BRCA2 carriers compared to BRCA1 carriers and a nonsignificant trend in OS advantage was detected in the same mutated population.…”

Section: Discussionmentioning

confidence: 99%

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The Different Impact of BRCA Mutations on the Survival of Epithelial Ovarian Cancer Patients: A Retrospective Single-Center Experience

et al. 2013

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Objectives: The objective of this study was to examine whether the oncologic outcomes of BRCA1-associated and BRCA2-associated ovarian cancers correlate differently. Methods: Genetic data and clinical characteristics were correlated with progression-free survival (PFS) and overall survival (OS). Results: Data from 147 BRCA-mutated patients (119 BRCA1-positive and 28 BRCA2-positive) were analyzed. At a median follow-up of 69 months, the median PFS was 27.2 and 45.46 months for BRCA1 and BRCA2 patients, respectively (p = 0.03). Median OS was 77.23 and 111.47 months for BRCA1 and BRCA2 patients, respectively (p = 0.08). Conclusion:BRCA2 mutations confer PFS and a trend to OS advantage compared with the BRCA1 mutation in BRCA-mutated epithelial ovarian cancer patients.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

The Different Impact of BRCA Mutations on the Survival of Epithelial Ovarian Cancer Patients: A Retrospective Single-Center Experience

et al. 2013

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“…234 Several studies have revealed ovarian cancer patients with BRCA1 as well as BRCA2 germline mutations to have a better chance of responding to platinumbased therapy as compared with patients wild type for BRCA1/2 in the primary setting as well as on tumour relapse. 233,[235][236][237][238] Most interestingly, there is experimental (BRCA2) but also results in human tumours (BRCA1 and BRCA2) revealing secondary mutations, restoring BRCA1/2 protein function, to be associated with acquired resistance toward platinum compounds. [239][240][241][242] The fact that mutations affecting both BRCA1 and BRCA2 seem to confer sensitivity to platinum compounds and to PARP inhibitors (see below) clearly implicates the Fanconi complex in drug sensitivity to these compounds.…”

Section: Homologous Recombination Repairmentioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

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Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

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“…Moreover, there is emerging evidence confirming no association between ERCC1 and platinum resistance in numerous tumour types including NSCLC [17] and ovarian cancer [18]. Nevertheless, the relationship between other mediators of DNA repair such as BRCA and response to platinum agents seemingly appears more consistent; whereby upregulation of BRCA1 (which mediates double strand break repair via homologous recombination) also induces platinum resistance [19] and conversely, BRCA mutations are a hallmark of platinum sensitivity [20]. The latter aspect is clearly exemplified by epithelial ovarian cancer in which at least 50% of cases harbour homologous recombination defects [21] which underpin the inherent platinum sensitivity of this disease at initial presentation.…”

Section: Introductionmentioning

confidence: 99%

Cisplatin versus carboplatin: comparative review of therapeutic management in solid malignancies

Woodward

Coward

2016

Critical Reviews in Oncology/Hematology

248

135

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2 Highlights Platinum analogues, cisplatin and carboplatin, represent some of the most active cytotoxic agents in clinical oncology and are the backbone of most chemotherapeutic regimens  Despite relative similarities in mechanisms of action and activities, there are significant differences in both efficacy and toxicities for both platinum analogues in various malignancies  Carboplatin is a useful alternative in situations where cisplatin is contraindicated and this is not universally at the expense of efficacy  Platinum resistance, both de novo and acquired, is inevitable and understanding the mechanisms of resistance is essential in improving outcomes  Despite the burgeoning era of targeted therapies, the role of efficient DNA damaging agents such as platinum salts remains paramount especially in combination with these novel drugs.3 AbstractThe platinum analogues, cisplatin and carboplatin, are among the most widely used chemotherapeutic agents in oncology. Both agents have a broad spectrum of clinical activity in numerous malignancies including gynaecological cancers, germ cell tumours, head and neck cancer, thoracic cancers and bladder cancer. Although the final mechanism of inducing tumour cell apoptosis is similar for both compounds, cisplatin has been shown to be more effective in treating specific tumour types. Whilst more favourable toxicity profiles are often associated with carboplatin, this can frequently translate to inferior response in certain malignancies. This review succinctly collates the evidence for the preferential use of these platinum analogues in particular settings in addition to the long-standing dilemma surrounding the paucity of biomarkers predicting response to these agents.

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BRCA1/2 mutations and expression: Response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer

Cited by 110 publications

References 31 publications

The Different Impact of <b><i>BRCA</i></b> Mutations on the Survival of Epithelial Ovarian Cancer Patients: A Retrospective Single-Center Experience

The Different Impact of <b><i>BRCA</i></b> Mutations on the Survival of Epithelial Ovarian Cancer Patients: A Retrospective Single-Center Experience

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Cisplatin versus carboplatin: comparative review of therapeutic management in solid malignancies

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