Brittany L. Bychkovsky, MD, MSc
Judy E. Garber, MD, MPH
Genetic testing for inherited cancer susceptibility is increasingly part of the care of cancer patients and their relatives. Early clinical guidelines recommended BRCA1/2 testing for women diagnosed with breast or ovarian cancer if they also have a significant family cancer history or Ashkenazi Jewish ancestry.1 More recently, clinical practice guidelines have evolved and now emphasize testing in cancer patients. Current National Comprehensive Cancer Network® guidelines endorse BRCA testing in all women with an ovarian cancer diagnosis and in those with any breast cancer at age ≤ 50 years or triple-negative breast cancer at age ≤ 60 years.1
The identification of a BRCA1/2 mutation has clinical relevance for cancer screening, prevention of additional primary tumors, and oncologic care even after a cancer diagnosis. In breast oncology, a patient’s BRCA status increasingly contributes to early clinical decisions regarding surgery, chemotherapy, and clinical trial options. Patients with nonmetastatic breast cancer and BRCA1/2 mutation are at a higher risk of a second breast cancer than average-risk women and often favor bilateral mastectomies for their initial cancer treatment to reduce the risk of contralateral breast malignancy.
Factors in Suboptimal Testing
In this context, as reviewed in this issue of The ASCO Post, Kurian and colleagues recently reported in JAMA on the rates of genetic testing for BRCA1/2 among women with a breast cancer diagnosis.2 Using 2013 to 2014 Surveillance, Epidemiology, and End Results (SEER) data (Los Angeles County and Georgia), they found that BRCA1/2 testing rates were suboptimal: only 29% of all patients in the cohort received BRCA1/2 genetic testing, yet 66% “wanted testing,” and many considered to be at high risk were neither offered genetic testing nor referred for genetic counseling. Women who were classified as high risk based on rigorous criteria did have higher genetic testing rates (52.9%) vs those deemed average risk (17.8%), but these rates are still low.2
“Identifying BRCA1/2 and other predisposing mutations can be lifesaving for breast cancer patients and their families, but it must be offered and the results interpreted appropriately and without discrimination in access based on race or ethnicity.”— Brittany L. Bychkovsky, MD, MSc, and Judy E. Garber, MD, MPH
This is a large study, and the use of SEER data reduces the selection that can bias this type of data. One prior study from Florida found similar results among black women with breast cancer aged < 50 years, where only 51% were referred for or received genetic counseling and/or BRCA1/2 testing.3 Overall, 36% underwent BRCA1/2 testing, of whom about half had no formal genetic counseling appointment.3 Receipt of genetic counseling was associated with referral, private insurance, and higher income at the time of diagnosis.3
In Kurian and colleagues’ work, multivariable analysis revealed that high-risk patients were less likely to have testing if they were older or Asian. It is not surprising that older age is associated with less testing, since older patients have a lower probability of carrying BRCA1/2 mutations. The finding that Asian race/ethnicity, and not Hispanic or black race/ethnicity, is associated with a lower likelihood of receiving BRCA1/2 testing is unexpected, since there is evidence describing disparities in breast cancer care for Hispanics and non-Hispanic blacks but not Asian women.4,5 For example, Armstrong et al found that black women with a family history of breast and/or ovarian cancer were less likely than white women to undergo genetic counseling, even after accounting for socioeconomic factors, attitudes, and physician discussions about testing.6 It is important to explore the barriers to BRCA1/2 testing among Asian women with breast cancer, since testing rates could potentially be improved with an intervention if cultural or logistical issues predominate. Overall, Kurian and colleagues’ paper demonstrates a very real need to improve genetic testing implementation rates for women of all races and ethnicities.
In their report, among high-risk women, 70.9% talked with any clinician about testing, whereas only 39.6% had a session with a genetic counselor. Among average-risk women, the respective numbers were 35.9% and 14.4%.2 These findings are noteworthy and could indicate that cancer clinicians are providing genetic counseling themselves and/or that they are not referring patients for genetic counseling and testing. If the former, it is important for breast oncology physicians, surgeons, and nurses to keep up to date on genetic issues. If the latter, education might again be helpful; or this may reflect the national shortage of genetic counselors available for timely provision of genetics services, particularly when clinical decisions must be made expeditiously.
There are clinical implications of appropriate genetic counseling in the context of identifying germline BRCA1/2 mutations. In a recent article in the Journal of Clinical Oncology, Kurian and colleagues examined the effect of identifying BRCA1/2 mutations on surgical decisions in women with breast cancer using the same SEER cohort as in the study published in JAMA.7 Among women categorized as at high risk for a mutation, 30% found to have no mutation underwent bilateral mastectomies, compared with 43% of those with a BRCA1/2 variant of uncertain significance and 80% of those with pathogenic BRCA1/2 or other pathogenic cancer susceptibility gene mutations. This trend was also observed among the “average-risk” population, where 51% found to have a BRCA variant of uncertain significance underwent bilateral mastectomy. The high rates of bilateral mastectomy among women with no mutation and with variants of uncertain significance, the majority of which are likely to ultimately be reclassified as benign polymorphisms, are quite concerning and strongly suggest a need to better counsel and educate both patients and their clinicians about how to interpret genetic test results.
The work of Kurian and colleagues clearly demonstrates that we are not providing cancer genetic services to women with breast cancer in anything close to an ideal manner. Furthermore, when BRCA1/2 variants are identified in women with breast cancer, there is clearly a misunderstanding of their potential significance, since carriers of variants of uncertain significance have been found to undergo bilateral mastectomy at a remarkable rate. The high rate of bilateral mastectomies in women with no detectable mutation speaks to the issues for women and their surgeons.
Genetic testing should help guide the management of women with breast cancer when the information is used properly. Identifying BRCA1/2 and other predisposing mutations can be lifesaving for breast cancer patients and their families, but it must be offered and the results interpreted appropriately and without discrimination in access based on race or ethnicity. Appropriate counseling ideally before and certainly after testing appears to be important, since genetic results should not be misinterpreted in ways that increase morbidity or mortality unnecessarily. Although genetic testing is more available in 2017, there is still a need to better integrate genetic services into oncology to improve the care of women with breast cancer. ■
Disclosure: Drs. Bychkovsky and Garber reported no conflicts ot interest.
1. National Comprehensive Cancer Network®: NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian. v2.2017. Available at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed May 3, 2017.
3. Cragun D, Bonner D, Kim J, et al: Factors associated with genetic counseling and BRCA testing in a population-based sample of young Black women with breast cancer. Breast Cancer Res Treat 151:169-176, 2015.
7. Kurian AW, Li Y, Hamilton AS, et al: Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol. April 12, 2017 (early release online).