Identifying and Testing BRCA Gene Variant Carriers Meeting NCCN Criteria
June 1, 2023
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By Alexandra Samborski, MD
University of Rochester Medical Center, NY
SYNOPSIS: A large percentage of patients who meet criteria for breast cancer gene (BRCA) testing based on family history do not have it completed until after a personal cancer diagnosis, thus missing the opportunity for risk-reducing strategies.
SOURCE: Lee SS, Rajeev P, Finning S, et al. Missed opportunities in the real-world genetic testing in BRCA gene variant carriers with cancers meeting NCCN criteria. Gynecol Oncol 2023;170:32-37.
Breast cancer gene (BRCA) 1 and BRCA2 are tumor suppressor genes, and patients with pathogenic variants are at increased risk of breast cancer, ovarian cancer, uterine serous cancer, pancreatic cancer, prostate cancer, and melanoma. The National Comprehensive Cancer Network (NCCN) has guidelines that recommend genetic counseling and testing for patients based on their family history or personal history of BRCA-related cancers. Testing is important, since it can guide treatment options and trigger cascade testing in family members, yet not all patients who meet criteria get tested. The aim of this study was to determine the proportion of patients who underwent genetic testing after diagnosis of a BRCA-related cancer and whether these patients met NCCN criteria for testing prior to their diagnosis.
This was a cross-sectional study involving patients from three hospitals with both BRCA pathogenic variants and BRCA-related cancers over a 20-year period. Data were collected via chart review. The NCCN guidelines (version 2.2021) were applied to each patient to determine if they met criteria for genetic testing and whether this was by personal or family history. Chi-squared and Fisher’s exact test were used for categorical variables, the Mann Whitney U test was used for non-parametric variables, and a multivariate logistic regression was used to assess variables associated with undergoing testing.
A total of 270 patients met inclusion criteria for the study. The median ages at the time of cancer diagnosis and genetic testing were 45 years and 49 years, respectively. Eighty percent of patients were white and 67.8% had private insurance. Eighty percent of patients had breast cancer, 20.7% had ovarian cancer, 2.6% had uterine serous cancer, 1.5% had melanoma, and 1.1% had pancreatic cancer. Of the 270 patients included, 229 (84.8%) underwent genetic testing after diagnosis with a BRCA-related cancer and 41 (15.2%) underwent genetic testing prior to their diagnosis. Of the 229 patients, 221 (96.5%) met at least one NCCN criterion for testing, and 166 (72.5%) met criteria for genetic testing based on family history alone and, thus, would have been eligible for testing prior to their diagnosis. Patients who underwent testing prior to their cancer diagnosis were more likely to have a family history of a known pathologic variant (75.6% vs. 24.5%; P < 0.001; odds ratio [OR], 0.10; 95% confidence interval [CI], 0.05-0.23). Of the 41 patients who underwent testing prior to a cancer diagnosis, 31 had a risk-reducing salpingo-oophorectomy and 29 underwent risk-reducing mastectomy. Patients who were publicly insured or uninsured were more likely to undergo testing after their cancer diagnosis (OR, 3.03; 95% CI, 1.09-8.40).
BRCA testing is an important aspect of medical care for patients who qualify either by family history or a personal history of high-risk cancer or cancer at a young age. Frequently, this testing is completed as a panel to assess for other pathologic variants that might contribute to a patient’s cancer risk. Timely testing allows for family planning, increased screening, risk-reducing measures such as surgery, and cascade testing for biologic relatives. Additionally, treatment options for patients diagnosed with these cancers may be determined based on their BRCA status. Despite these benefits, the rate of genetic testing for BRCA variants is far less than those who meet criteria for it. Previously reported rates of testing for ovarian cancer range from 30% to 60%.1,2 These low rates of genetic testing for eligible patients represent missed opportunities for disease prevention, earlier diagnosis, or optimal treatment. The magnitude of the downstream effects of this is what makes the lack of testing so devastating.
The reasons for the discrepancy in testing are multifactorial. Access to genetic counseling, appropriate referrals, and financial consequences are some reasons for this discrepancy. One of the primary reasons is the shortage of genetic counselors. Almost one-third of the U.S. population does not live within a 30-minute drive of a genetic counselor, and the number of genetic counselors varies from 0.17 to 5.7 per 100,000 people based on the state.3 Strategies to increase access to genetic counseling have included using multidisciplinary teams, embedding genetic counselors in clinics, and using telemedicine.2,4,5 The genetic testing itself and the results are becoming much more complex, and, thus, ensuring patients receive appropriate counseling regarding testing and the clinical implications of results is crucial.
Although there are criteria for who should be referred for genetic counseling and testing, there still are barriers to patients being referred. Guidelines for genetic testing have become more inclusive over time, and provider knowledge regarding who qualifies may not be up to date. Patients may not recall the exact details of their family cancer histories, and it can take significant time to collect a thorough family history. In this study, more than 70% of patients would have been eligible for testing prior to their cancer diagnosis based on family history. This exhibits just how difficult it can be to identify these patients and get appropriate testing for them. For patients with a remote personal history of a BRCA-related cancer, they may not have received testing when diagnosed per guidelines at that time but may currently be candidates given newer testing recommendations. These situations can make it difficult to determine who meets criteria for referral.
The financial burden also is a barrier. Although insurance coverage for genetic testing has improved, there still are patients who face out-of-pocket costs for genetic counseling and testing.6 The costs of genetic testing and any risk-reducing measures must be weighed against the cost of treatment for a potentially preventable cancer. Studies have shown that genetic testing is cost effective, and continuing to improve insurance coverage for these referrals and testing is warranted.7,8
Unfortunately, there are significant disparities in genetic counseling referrals and testing for patients, which likely contributes to the disparities in overall cancer care. Previous studies have shown that patients with breast or ovarian cancer who are Black or uninsured have lower rates of genetic testing.1 A systematic review showed that 26% of Black patients underwent genetic testing compared to 40% of white patients. Additionally, 23% of uninsured patients received genetic testing, while 38% of insured patients did.9
Clearly, testing for BRCA and other genes associated with hereditary breast and ovarian cancer syndromes is important so that patients can make informed decisions regarding screening and risk-reducing measures. This study showed a high proportion of patients undergoing risk-reducing measures when a pathologic variant was identified. Ideally, cascade testing for at-risk family members would be performed as well. High rates of testing could significantly decrease the burden of these cancers. Increasing the identification of patients meeting criteria and access to genetic counseling are important steps to make this happen.
- Kurian AW, Ward KC, Howlader N, et al. Genetic testing and results in a population based cohort of breast cancer patients and ovarian cancer patients. J Clin Oncol 2019;37:1305-1315.
- Rana HQ, Kipnis L, Hehir K, et al. Embedding a genetic counselor into oncology clinics improves testing rates and timeliness for women with ovarian cancer. Gynecol Oncol 2021;160:457-463.
- Bellaiche MMJ, Fan W, Walbert HJ, et al. Disparity in access to oncology precision care: A geospatial analysis of driving distances to genetic counselors in the U.S. Front Oncol 2021;11:689927.
- Bradbury A, Patrick-Miller L, Harris D, et al. Utilizing remote real-time videoconferencing to expand access to cancer genetic services in community practices: A multicenter feasibility study. J Med Internet Res 2016;18:e23.
- Kishan AU, Gomez CL, Dawson NA, et al. Increasing appropriate BRCA1/2 mutation testing: The role of family history documentation and genetic counseling in a multidisciplinary clinic. Ann Surg Oncol 2016;23(Suppl 5):634-641.
- Grant P, Langlois S, Lynd LD, et al. Out-of-pocket and private pay in clinical genetic testing: A scoping review. Clin Genet 2021;100:504-521.
- Teppala S, Hodgkinson B, Hayes S, et al. A review of the cost-effectiveness of genetic testing for germline variants in familial cancer. J Med Econ 2023;26:19-33.
- Koldehoff A, Danner M, Civello D, et al. Cost-effectiveness of targeted genetic testing for breast and ovarian cancer: A systematic review. Value Health 2021;24:303-312.
- Lin J, Sharaf RN, Saganty R, et al. Achieving universal genetic assessment for women with ovarian cancer: Are we there yet? A systematic review and meta-analysis. Gynecol Oncol 2021;162:506-516.
A large percentage of patients who meet criteria for breast cancer gene (BRCA) testing based on family history do not have it completed until after a personal cancer diagnosis, thus missing the opportunity for risk-reducing strategies.
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