Environmental or system factors
Accessibility of genetic counseling and testing is a common barrier to cascade testing. Family members may be geographically remote and connecting them to counseling and testing can be challenging. Working with local genetic counselors can facilitate this process. Insurance coverage of testing is a common perceived barrier; however, many testing companies now provide cascade testing free of charge if within a certain window from the initial test. Despite this, patients often site cost as a barrier to undergoing testing. Concerns about insurance coverage are common after a positive result. The Genetic Information Nondiscrimination Act of 2008 prohibits discrimination against employees or insurance applicants because of genetic information. Life insurance or long-term care policies, however, can incorporate genetic testing information into policy rates, so patients should be recommended to consider purchasing life insurance prior to undergoing genetic testing. This is especially important if the person considering testing has not yet been diagnosed with cancer.
Implications of a positive result
Family members who receive a positive test result should be referred for genetic counseling and to the appropriate specialists for evidence-based screening and discussion for risk-reducing surgery (FIGURE).7 For mutations associated with hereditary breast and ovarian cancer, referral to breast and gynecologic surgeons with expertise in risk reducing surgery is critical as the risk of diagnosing an occult malignancy is approximately 1%.22 Surgical technique with a 2-cm margin on the infundibulopelvic ligament and pathologic evaluation with sectioning and extensive examination of the fimbriated end of the tubes (SEE-Fim technique) is recommended for mutation carriers. Additionally, evidence has emerged suggesting an increased risk of uterine serous cancer in BRCA1 carriers necessitating a discussion about risk-reducing hysterectomy in these patients.23 Following risk reducing surgery, surgical menopause can have significant impacts on patients’ health and well-being. Treatment options including hormone replacement therapy can be considered.24 To minimize recovery time burdens for patients, combination surgeries with breast, plastic, and gynecology specialties can be offered.
Patient resources: decision aids, websites
As genetic testing becomes more accessible and people are tested at younger ages, studies examining the balance of risk reduction and quality of life (QOL) are increasingly important. Fertility concerns, effects of early menopause, and the interrelatedness between decisions for breast and gynecologic risk reduction should all be considered in the counseling for surgical risk reduction. Patient decision aids can help mutation carriers navigate the complex information and decisions.25 Websites specifically designed by advocacy groups can be useful adjuncts to in-office counseling (Facing Our Risk Empowered, FORCE; Facingourrisk.org).
Family letters
The American College of Obstetricians and Gynecologists recommends an ObGyn have a letter or documentation stating that the patient’s relative has a specific mutation before initiating cascade testing for an at-risk family member. The indicated test (such as BRCA1) should be ordered only after the patient has been counseled about potential outcomes and has expressly decided to be tested.26 Letters, such as the example given in the American College of Obstetricians and Gynecologists practice bulletin,26 are a key component of communication between oncology providers, probands, family members, and their primary care providers. ObGyn providers should work together with genetic counselors and gynecologic oncologists to determine the most efficient strategies in their communities.
Technology
Access to genetic testing and genetic counseling has been improved with the rise in telemedicine. Geographically remote patients can now access genetic counseling through medical center–based counselors as well as company-provided genetic counseling over the phone. Patients also can submit samples remotely without needing to be tested in a doctor’s office.
Databases from cancer centers that detail cascade genetic testing rates. As the preventive impact of cascade genetic testing becomes clearer, strategies to have recurrent discussions with cancer patients regarding their family members’ risk should be implemented. It is still unclear which providers—genetic counselors, gynecologic oncologists, medical oncologists, breast surgeons, ObGyns, to name a few—are primarily responsible for remembering to have these follow-up discussions, and despite advances, the burden still rests on the cancer patient themselves. Databases with automated follow-up surveys done every 6 to 12 months could provide some aid to busy providers in this regard.
Emerging research
If gynecologic risk-reducing surgery is chosen, clinical trial involvement should be encouraged. The Women Choosing Surgical Prevention (NCT02760849) in the United States and the TUBA study (NCT02321228) in the Netherlands were designed to compare menopause-related QOL between standard risk-reducing salpingo-oophorectomy (RRSO) and the innovative risk-reducing salpingectomy with delayed oophorectomy for mutation carriers. Results from the nonrandomized controlled TUBA trial suggest that patients have better menopause-related QOL after risk-reducing salpingectomy than after RRSO, regardless of hormone replacement therapy.27 International collaboration is continuing to better understand oncologic safety. In the United States, the SOROCk trial (NCT04251052) is a noninferiority surgical choice study underway for BRCA1 mutation carriers aged 35 to 50, powered to determine oncologic outcome differences in addition to QOL outcomes between RRSO and delayed oophorectomy arms.
Returning to the case
The patient and her family underwent genetic counseling. The patient’s 2 daughters, each in their 50s, underwent cascade genetic testing and were found to carry the same pathogenic mutation in BRCA2. After counseling from both breast and gynecologic surgeons, they both elected to undergo risk reducing bilateral salpingo-oophorectomy with hysterectomy. Both now complete regular screening for breast cancer and melanoma with plans to start screening for pancreatic cancer. Both are currently cancer free.
Summary
Cascade genetic testing is an efficient strategy to identify mutation carriers for hereditary breast and ovarian cancer syndrome. Implementation of the best patient-centric care will require continued collaboration and communication across and within disciplines. ●
Summary of recommendations
Cascade, or targeted, genetic testing within families known to carry a hereditary mutation in a cancer susceptibility gene should be performed on all living first-degree family members over the age of 18. All mutation carriers should be connected to a multidisciplinary care team (FIGURE) to ensure implementation of evidence-based screening and risk-reducing surgery for cancer prevention. If gynecologic risk-reducing surgery is chosen, clinical trial involvement should be encouraged.
Cascade, or targeted, genetic testing within families known to carry a hereditary mutation in a cancer susceptibility gene should be performed on all living first-degree family members over the age of 18. All mutation carriers should be connected to a multidisciplinary care team (FIGURE) to ensure implementation of evidence-based screening and risk-reducing surgery for cancer prevention. If gynecologic risk-reducing surgery is chosen, clinical trial involvement should be encouraged.