Highlights
- •The BRCAPRO and Myriad models were assessed in 232 Korean ovarian cancer patients.
- •Both models were sufficiently specific and sensitive in this population.
- •The BRCA mutation risk was overestimated in those with a family history of cancer.
- •The BRCA mutation risk was underestimated in those without a family history.
- •These results support a universal testing strategy for all ovarian cancer patients.
Abstract
Objective
To evaluate the predictive efficacies including sensitivity and positive predictive
value of the genetic risk prediction model BRCAPRO and the Myriad BRCA risk calculator
in Korean ovarian cancer patients.
Methods
Individuals undergoing genetic testing for BRCA mutations from November 2010–August 2016 were recruited from the Department of Obstetrics
and Gynecology at a single institute in Korea. The observed BRCA1 and BRCA2 mutation statuses were compared with the predicted carrier probabilities using BRCAPRO
and the Myriad BRCA risk calculator.
Results
Two hundred thirty-two patients were recruited, of whom 99.1% (230/232) were of Korean
ethnicity. Of the 232 individuals, 206 and 26 had ovarian and double primary breast/ovarian
cancer, respectively. Thirty-six individuals had a family history of breast/ovarian
cancer in first-degree relatives. Fifty-seven patients (24.6%) tested positive for
BRCA mutation (41 BRCA1, 16 BRCA2). The mean BRCAPRO and Myriad scores for all patients were 6.4% and 7.7%, respectively.
The scores were significantly higher for patients with positive BRCA mutation status
(29.0% vs. 6.1%, P < 0.001, 12.1% vs. 7.7%, P < 0.001, respectively). For all patients, the respective areas under the receiver operating
characteristics curves were 0.720 and 0.747 for the BRCAPRO and Myriad models to predict
the risk of carrying a BRCA mutation. Both models overestimated the mutation probability
in patients with a family history of breast/ovarian cancer (1.55-fold and 1.50-fold,
respectively) and underestimated the probability in patients without a family history
(both, 0.54-fold).
Conclusion
BRCAPRO and Myriad seem to be acceptable risk assessment tools for determining the
risk of carrying BRCA mutations in Korean ovarian cancer patients.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Gynecologic OncologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium.Am. J. Hum. Genet. 1993; 52: 678-701
- Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2.Am. J. Hum. Genet. 1998; 62: 145-158
- The BOADICEA model of genetic susceptibility to breast and ovarian cancer.Br. J. Cancer. 2004; 91: 1580-1590
- Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals.J. Clin. Oncol. 2002; 20: 1480-1490
- A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO.J. Med. Genet. 2004; 41: 474-480
- Log odds of carrying an ancestral mutation in BRCA1 or BRCA2 for a defined personal and family history in an Ashkenazi Jewish woman (LAMBDA).Breast Cancer Res. 2003; 5: R206-R216
- BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model.J. Clin. Oncol. 2007; 25: 4635-4641
- Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics.J. Med. Genet. 2008; 45: 425-431
- Evaluating the performance of the breast cancer genetic risk models BOADICEA, IBIS, BRCAPRO and Claus for predicting BRCA1/2 mutation carrier probabilities: a study based on 7352 families from the German Hereditary Breast and Ovarian Cancer Consortium.J. Med. Genet. 2013; 50: 360-367
- BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.J. Clin. Oncol. 2002; 20: 2701-2712
- Optimal selection of individuals for BRCA mutation testing: a comparison of available methods.J. Clin. Oncol. 2006; 24: 707-715
- Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO.J. Natl. Cancer Inst. 2002; 94: 844-851
- Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients.Breast Cancer Res. Treat. 2012; 134: 1189-1197
- J. Clin. Oncol. 1996; 14 (discussion 7–40): 1730-1736
- A new definition of genetic counseling: National Society of Genetic Counselors' Task Force report.J. Genet. Couns. 2006; 15: 77-83
- Validity of models for predicting BRCA1 and BRCA2 mutations.Ann. Intern. Med. 2007; 147: 441-450
- Performance of prediction models for BRCA mutation carriage in three racial/ethnic groups: findings from the Northern California Breast Cancer Family Registry.Cancer Epidemiol. Biomark. Prev. 2009; 18: 1084-1091
- Prediction of BRCA mutations using the BRCAPRO model in clinic-based African American, Hispanic, and other minority families in the United States.J. Clin. Oncol. 2009; 27: 1184-1190
- Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry.JAMA. 2005; 294: 1925-1933
- Performance of BRCA1/2 mutation prediction models in Asian Americans.J. Clin. Oncol. 2008; 26: 4752-4758
- Underestimation of risk of a BRCA1 or BRCA2 mutation in women with high-grade serous ovarian cancer by BRCAPRO: a multi-institution study.J. Clin. Oncol. 2014; 32: 1249-1255
- Characteristics of women with ovarian carcinoma who have BRCA1 and BRCA2 mutations not identified by clinical testing.Gynecol. Oncol. 2013; 128: 483-487
- Keeping it simple: genetics referrals for all invasive serous ovarian cancers.Gynecol. Oncol. 2013; 130: 329-333
Article info
Publication history
Published online: February 01, 2017
Accepted:
January 22,
2017
Received in revised form:
January 20,
2017
Received:
December 7,
2016
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
