Genetic testing and counseling for BRCA mutation carriers and other high-risk breast cancer patients

Genetic counselors at Penn Medicine’s Basser Center for BRCA integrate research and clinical practice to help providers know when genetic testing and counseling are appropriate for patients considered at high risk for breast cancer.

Genetic counselors are specialized in knowing not only the intricacies of genetics as they apply to disease, but of understanding what it is to be afflicted by genetic disease. Genetic counseling has an especially prominent place at the Basser Center for BRCA, the nation’s first comprehensive center for men and women with BRCA-related cancers.

An overview of BRCA1 and BRCA2

The genes BRCA1 and BRCA2 are universal and heritable. Their normal role in both men and women is to promotes the repair of DNA and suppress the unchecked cell growth typical of cancer. However, genetic or somatic (non-heritable) mutations of either gene can impair this process, leading to genomic instability and increasing the risk of cancers of the breast, ovary, pancreas, and prostate, among other malignancies.

Individualized risk assessments and genetic counseling

Once a patient is referred to the Basser Center, genetic counselors provide comprehensive services, including individualized risk and psychosocial assessments, discussion of testing options, interpretation of results, and facilitation of family member or ‘cascade’ testing. Through outreach and provider education, the Center also works to ensure that individuals at increased genetic risk are identified and referred to appropriate care.

Among the Basser Center’s dedicated counselors, Jacquelyn Powers, MS, LCGC, manages the facilitation of risk assessment and genetic testing for heritable breast, ovarian, and gastrointestinal cancer syndromes. A senior licensed genetic counselor, Powers is an Associate Director of Genetic Counseling at Penn Medicine.

“My role is essentially in consultation, seeing individuals who might have a personal or family history of, for example, breast cancer,” she said in a recent interview. “In walking through a patient’s personal and family history, I provide a risk assessment, or pretest probability that by doing genetic testing, we might find or uncover a high-risk disease-causing mutation.”

The next step, Powers says, is to arm her patients with anticipatory information should the result come back positive for a mutation.

“We explain what that result might mean, from a risk perspective, and a management or long-term care perspective,” she explains. “We talk about the associated cancer risks and the potential test result outcomes that could be completely negative or normal.”

Genetic testing may result in a finding of uncertain significance. Often a source of anxiety for patients, most variants of uncertain significance are downgraded to benign on further testing.

Family history and background concerns

Because BRCA is heritable, early identification and outreach to at-risk family members is a chief concern in BRCA counseling.

“If we can identify the source of cancer risk in a family and link it to a BRCA mutation, we can offer what’s called informative genetic testing, which allows unaffected at-risk family members to know whether or not they’re at high risk,” Powers says.

Because carrying a germline mutation for BRCA makes one eligible for certain therapies or precision medicine, she adds, identifying people upstream of a cancer diagnosis is essential for therapeutic decision making.

Slightly more than half of the people receiving genetic testing or evaluation at the Basser Center have an active or past diagnosis of cancer. The remainder have never had cancer. The latter individuals, both male and female, are referred to the Center on the basis of a known mutation in the family, or a strong personal or family history of ovarian, pancreatic, prostate, or breast cancer—and for other reasons.

“Just being of known Ashkenazi Jewish descent is enough to have a conversation about considerations for BRCA testing,” Powers says. This is based upon the 1 in 40 chance that an Ashkenazi Jewish individual carries either a BRCA1 or BRCA2 mutation.

Who should be tested: Research-based referral recommendations

Genetic counselors at the Basser Center recommend that providers refer patients with any of the following criteria for evaluation or testing:

• A diagnosis of breast cancer under age 65, especially those under age 50
• Colon cancer under age 50 or any colon cancer any age with deficient mismatch repair protein staining via immunohistochemistry (IHC)
• A family member has a known cancer predisposition gene mutation
• Ashkenazi Jewish ancestry
• Bilateral or triple negative breast cancer
• A personal or family history of breast, ovarian, pancreatic, high-risk prostate, or male breast cancer

Coordinated high-risk management

For patients who receive a positive genetic test result, care coordination can present a significant challenge. At the time of disclosure, Jacquelyn Powers says, the result and its association with specific risks are presented to the patient. What happens next depends on a variety of factors including the category of risk, patient engagement with guideline-concordant care, as well as patient communication and coping with a new genetic diagnosis.

“Not all genes are built the same way,” Powers explains. “So we categorize them into high-risk genes, moderate risk genes, and then genes that have preliminary evidence.”

All BRCA mutations are considered high risk; however, mutations in other (non-BRCA) genes that may appear in screening, including ATM, CHEK2, and RAD51C/D, are considered to carry moderate risk for breast and ovarian cancers.

Whether patients carry moderate or high-risk mutations at the Basser Center, all are connected with a physician with interest and expertise in the management of hereditary cancer syndromes who then becomes the central point of contact or “quarterback” for all aspects of their care specific to their gene mutation. This is a differentiator for the program, Powers observes, because patients are not left to piece together their own care once diagnosed. There are certain hereditary cancer syndromes that are mainly overseen by other Penn colleagues and collaborators. The respective teams do a nice job of coordination and pivoting referrals, when needed.

“What differentiates our provider team, our genetic counselors and physicians, is their deep expertise.” Powers says. “When patients come to Penn, they have someone to consolidate and organize their care, and can learn about what research opportunities they may enroll in.”

When appropriate, the oncologist refers patients to relevant departments or programs within Penn Medicine, such as gynecologic oncology, urology, imaging and radiology, surgical oncology, breast reconstruction, and radiation oncology. Eligible patients may also be referred to and evaluated for participation in clinical trials and research studies.

Advancing care through genetic cancer research

BRCA-related breast cancer is a complex disease with ongoing questions around cancer biology, precise genetic risks, and other related factors. A core focus of the Basser Center is supporting translational research aimed at improving early detection and developing new preventive strategies for people with BRCA1 and BRCA2 mutations.

Through a comprehensive grants program, Basser Center investigators and external collaborators from around the world conduct research designed to advance prevention and treatment of BRCA-associated breast cancer.

Ongoing cancer clinical trials include:

• Vaccine in BRCA1/2 Carriers: Penn Medicine researchers are testing an experimental vaccine to potentially prevent cancer in patients with BRCA1 or BRCA2 mutations.
• Cancer Risk Evaluation Program (CREP) Biobank: Researchers will use this repository to identify blood biomarkers to develop a new screening test for the early detection of breast and ovarian cancers.
• Responses to Genetic Risk Modifier Testing Among Women With BRCA1/2 Mutations: In collaboration with Memorial Sloan Kettering Cancer Center and the Dana Farber Cancer Institute, researchers are evaluating the impact of polygenic risk score on decision-making.

Additional enrolling clinical trials are available through the Basser Center.

Genetic counseling at the Basser Center

A combined effort of basic scientists, clinician scientists, medical oncologists, the Basser Center is a focal point for dedicated genetic counseling in the BRCA-associated diseases. Here, genetic counselors participate in outreach to ensure that individuals who can and should think about genetic evaluation for BRCA and other hereditary susceptibility genes receive information about how to go about getting tested, or, if a known mutation carrier, where to find longitudinal care and treatment in their communities.

Referrals and Consultations

To refer a patient for genetic counseling at Penn Medicine, please call 215-349-9093 to speak to a member of the CREP team, or email CREPteam@pennmedicine.upenn.edu.