A multi-institution study of the accuracy of BRCAPRO in predicting BRCA1/BRCA2 mutations in women with ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1520-1520
Author(s):  
Molly S Daniels ◽  
Sheri Babb ◽  
Robin King ◽  
Diana Urbauer ◽  
Christopher I. Amos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Cancer Patients ◽  
Goodness Of Fit ◽  
Brca2 Mutation ◽  
Model Performance ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Goodness Of Fit Test

1520 Background: 10-15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation, with significant management implications for both patients and relatives. Genetic testing decisions are guided in part by the estimated likelihood of identifying a mutation. The BRCAPRO model uses personal and family history of breast and ovarian cancer to calculate the likelihood of a BRCA1/2 mutation. This study’s purpose was to assess the ability of BRCAPRO to accurately determine this likelihood. Methods: BRCAPRO scores were calculated using CancerGene v5.1 for 589 ovarian cancer patients referred for genetic counseling at three institutions. The study population was divided into quintiles by BRCAPRO score, with cutpoints chosen such that each quintile represented 20% of the sample. Chi-square goodness-of-fit test was used to compare observed BRCA1/2 mutations to the number predicted. ANOVA models were used to assess factors impacting BRCAPRO accuracy. Results: 180/589 (31%) ovarian cancer patients tested positive for a BRCA1/2 mutation. At BRCAPRO scores under 40%, more mutations were observed than expected (93 observed vs. 34.1 expected, p<0.001). If patients with BRCAPRO scores <10% had not been offered genetic testing, almost one-third of mutations (51/180, 28%) would have been missed. Multivariate analysis demonstrated that BRCAPRO underestimated risk for high grade serous ovarian cancers but overestimated risk for other histologies (p<0.0001), underestimation increased as age at diagnosis decreased (p=0.02), and model performance varied by institution (p=0.02). Conclusions: Ovarian cancer patients classified as low risk by BRCAPRO are more likely to test positive than predicted, therefore the BRCAPRO prediction could falsely reassure patients considering genetic testing. BRCAPRO performance could be improved by incorporating factors such as ovarian cancer histology. Alternatively, given the high prevalence of BRCA1/2 mutations in high grade serous ovarian cancer and the apparent limitations of using family history to predict mutation probability, BRCA1/2 genetic testing could be offered to high grade serous ovarian cancer patients regardless of family history.

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

2014 ◽  
Vol 32 (12) ◽  
pp. 1249-1255 ◽  
Author(s):  
Molly S. Daniels ◽  
Sheri A. Babb ◽  
Robin H. King ◽  
Diana L. Urbauer ◽  
Brittany A.L. Batte ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Brca2 Mutation ◽  
Model Performance ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cancer History ◽  
Family Cancer History ◽  
Brca1 Brca2

Purpose Identification 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. Methods BRCAPRO 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. Results One 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 < .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 < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02). Conclusion Patients 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.

Molecular predictors of the outcome of paclitaxel plus carboplatin neoadjuvant therapy in high-grade serous ovarian cancer patients

2021 ◽  
Author(s):  
Anna P. Sokolenko ◽  
Tatiana V. Gorodnova ◽  
Ilya V. Bizin ◽  
Ekaterina Sh. Kuligina ◽  
Khristina B. Kotiv ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery

2020 ◽  
Vol 7 (6) ◽  
pp. 1805094
Author(s):  
Maria Bååth ◽  
Sofia Westbom-Fremer ◽  
Laura Martin de la Fuente ◽  
Anna Ebbesson ◽  
Juliette Davis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Residual Disease ◽  
High Grade ◽  
Advanced Stage ◽  
Serous Ovarian Cancer ◽  
Debulking Surgery

scholarly journals Is BRCA mutational status a predictor of platinum-based chemotherapy related hematologic toxicity in high-grade serous ovarian cancer patients?

2019 ◽  
Vol 154 (1) ◽  
pp. 138-143 ◽  
Author(s):  
Federica Tomao ◽  
Lucia Musacchio ◽  
Federica Di Mauro ◽  
Serena Maria Boccia ◽  
Violante Di Donato ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Hematologic Toxicity ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Mutational Status ◽  
Platinum Based Chemotherapy

Moving Toward Personalized Medicine: Treatment-Focused Genetic Testing of Women Newly Diagnosed With Ovarian Cancer

2010 ◽  
Vol 20 (5) ◽  
pp. 704-716 ◽  
Author(s):  
Alison H. Trainer ◽  
Bettina Meiser ◽  
Kaaren Watts ◽  
Gillian Mitchell ◽  
Kathy Tucker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Mutation Frequency ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Age At Onset ◽  
Prognostic Significance ◽  
Brca1 And Brca2 ◽  
Germline Brca Mutation

Objectives:The presence of a germline BRCA mutation defines a genotype-specific group of women whose invasive ovarian cancer is associated with an increasingly well-defined prognostic and chemosensitivity biological profile. To determine the criteria that may be used to select patients for BRCA treatment-focused genetic testing, we performed a systemic literature search of studies that assessed BRCA1 and BRCA2 mutation frequency in women with ovarian cancer unselected for family history. The results are discussed with regard to the added clinical value gained by identifying a germline BRCA mutation at the time of the ovarian cancer diagnosis.Methods:BRCA-related studies were identified in the CD-ROM databases PubMed (including MEDLINE), PsychINFO, and CINAHL and included in the review if they met the following criteria: they (a) assessed mutation frequency in women with ovarian cancer who were unselected for family history and ethnicity, (b) were published in a peer-review journal, (c) between January 1997 and October 2009, and (d) in the English language.Results:Studies investigating the prevalence of BRCA1 or BRCA2 mutations in ovarian cancer patients unselected for family history or ethnicity have found a pathological BRCA mutation rate of approximately 3% to 17%. Without a significant family history, specific features that may be used to target treatment-focused BRCA testing in the ovarian cancer setting include young age at onset (<50 years), high-grade serous tumor histology, and specific ethnicity associated with known BRCA founder mutations.Conclusions:We believe that given the growing appreciation of the prognostic significance of BRCA mutations and the differential chemosensitivity shown by these tumors, as well as the potential of novel agents such as poly(ADP-ribose) polymerase inhibitors, the identification of a germline BRCA mutation concurrent with a new diagnosis of ovarian cancer will significantly impact on tailoring personalized ovarian management in the future.

scholarly journals Low expression of circular RNA hsa_circ_0078607 predicts poor prognosis in high-grade serous ovarian cancer

2020 ◽  
Author(s):  
Nan Zhang ◽  
Zhiyou Yang ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Jiani Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Diagnosis And Prognosis ◽  
Low Expression

Abstract Background Ovarian cancer remains one of the most lethal malignancies in women which is typically diagnosed at a late stage and has no effective screening strategy. It is essential to explore novel biomarkers for the diagnosis and prognosis of ovarian cancer, as well as therapeutic targets. Recent studies have shown that circRNAs participate in ovarian cancer progression by regulating various processes and being able to act as potential biomarkers for ovarian cancer diagnosis and prognosis. In the present study we aimed to explore the prognostic role of circ_0078607 in high-grade serous ovarian cancer. Results The expression of circ_0078607 in 49 high-grade serous ovarian cancer and adjacent non-cancerous tissue samples were detected by quantitative real-time polymerase chain reaction (qRT-PCR). We noticed that circ_0078607 expression was significantly downregulated in ovarian cancer tissues compared with adjacent non-cancerous tissues. Besides, patients with low circ_0078607 expression exhibited parameters associated with poor prognosis, including advanced FIGO stage and higher serum CA125 level. Kaplan-Meier survival curve analysis showed that both progression-free survival and overall survival were significantly shortened in patients with low circ_0078607 expression. Cox regression model analysis showed that low expression of circ_0078607 was an adverse prognostic indicator for high-grade serous ovarian cancer patients. Conclusions Low expression of circ_0078607 might be an adverse prognostic indicator for high-grade serous ovarian cancer patients.

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