How to spot heritable breast cancer: A primary care physician’s guide
ABSTRACTBecause breast cancer is common, primary care physicians will encounter many patients who have a personal or family history of it. Many patients may benefit from referral to a cancer genetics program for assessment, genetic counseling, and consideration of genetic testing. This article discusses the complexities of risk assessment in cancer genetics (focusing on breast cancer), and highlights the primary care physician’s role in identifying and caring for patients at risk.
KEY POINTS
- Primary care physicians play a critical role in identifying patients at risk of inherited health problems.
- Hereditary cancers are important to detect because the age of onset is early, multiple primary cancers can develop, and cancer predisposition may be inherited.
- Hereditary syndromes account for only a minority of cases of breast cancer, but women who bear the responsible mutations have an extremely high risk.
- Patients with hereditary breast cancer syndromes and those with familial breast cancer can benefit from heightened surveillance for breast cancer.
- Cancer genetics risk assessment ensures that the correct genetic testing is offered to the most appropriate patients, with personalized interpretation of results and provision of future management recommendations based on the individual patient’s personal and family history.
What is a cancer-focused genetic counseling session?
The tenets of genetic counseling, described previously in this series,7 are relevant to hereditary cancer syndromes. Cancer risk assessment and genetic counseling constitute the process of identifying and counseling individuals at risk of familial or hereditary cancer.8
As in other genetic counseling scenarios, a detailed pedigree (family tree) is taken, and this information, along with the patient’s personal medical history, allows a genetics specialist to determine if the presentation is most suggestive of sporadic, familial, or hereditary cancer.
A common misconception among patients is that there is a single genetic test for hereditary breast cancer, when in fact many highly penetrant predisposition genes have been linked to heightened risk (see below). The syndromes summarized in Table 35,9–18 are part of the differential diagnosis for every patient presenting with a personal or family history of breast cancer, and the detailed information from the personal and family history, ascertained during the assessment, ensures the right syndrome is explored within a family.
Cancer-focused genetic counseling may also help a patient or family process the psychological and emotional responses that can occur when cancer risk is discussed: eg, fear of cancer and death; guilt a parent may feel for passing on a genetic predisposition; and survivor guilt experienced by family members who test negative.
Genetic counselors are trained to recognize patients who may benefit from additional counseling. Not all patients pursuing cancer-focused genetic testing need a thorough evaluation by a psychologist, unlike those with adult-onset neurodegenerative conditions such as Huntington disease. Rather, the genetic counselor discusses the psychological implications of cancer-focused genetic testing and can refer the patient to a psychologist, therapist, social worker, or others if he or she feels the patient may benefit.8
Some patients come to a genetic counseling session with concerns about whether their insurance will pay for testing, and about whether they will face discrimination because of the testing results. In most situations, genetic testing is deemed medically necessary and is covered by the patient’s insurance. When testing is necessary, genetic counselors are skilled at preauthorizing it and writing letters of medical necessity. They are also familiar with laws and regulations that protect patients, such as the Genetic Information Nondiscrimination Act, which protects patients from insurance and employment discrimination.
Because a cancer-focused genetic counseling session typically lasts 1 hour, the counselor has enough time to address these and any other concerns that might prevent a patient who is otherwise interested in genetic testing from pursuing it.
HOW CAN GENETIC TESTING HELP?
Genetic testing for hereditary cancer syndromes can have personal benefit for the patient and at-risk family members.
Note that the syndromes in Table 3 all increase the risk of more than one type of cancer. Patients with these syndromes frequently receive care from multiple subspecialists to mitigate those risks. Guidelines exist for each of these syndromes and, if followed, may prevent the morbidity and possibly death from the genotype-specific cancers that would otherwise be in the patient’s future. For patients found to have a hereditary cancer syndrome, medical management options include more-frequent cancer screening or surveillance, prophylactic surgery, and preventive medical treatment, which will be reviewed in a future article in this series.
Identifying the specific mutation in one family member allows at-risk relatives, both female and male, to then take advantage of predictive testing, with genetic counseling. If they test positive for the risk-increasing mutation, they too can take advantage of the management options for people at high risk. If they test negative, they can continue to undergo the same screening as recommended for the general population. Also, they may be relieved to know that their cancer risk is no greater than that in the general population.
The American Society of Clinical Oncology9 recommends genetic counseling and testing when all of the following are true:
- There is a personal or family history suggesting genetic cancer susceptibility
- The test can be adequately interpreted
- The results will aid in the diagnosis or influence the medical or surgical management of the patient or family at hereditary risk of cancer.
Professional society guidelines also recommend that genetic testing be done only with genetic counseling before and after.5,6,8 The National Society of Genetic Counselors provides a list of clinical genetic counselors, organized by geographical area, at www.nsgc.org.
PATIENT 1 RECEIVES GENETIC TESTING AND COUNSELING
Let’s return to the Ashkenazi Jewish patient who has a personal and family history of breast cancer, whom you referred for cancer genetics consultation and who attends this appointment. A detailed personal and family history is gathered, and a brief physical examination is done, which reveals that the patient has macrocephaly and a history of multiple uterine fibroids.
The genetic differential diagnosis for your patient includes hereditary breast and ovarian cancer syndrome (resulting from mutations in the BRCA1 and BRCA2 genes) and Cowden syndrome (from mutations in the PTEN gene) (TABLE 3). The counselor uses BRCAPRO, a statistical risk-assessment tool that estimates a patient’s risk of harboring a BRCA1 or BRCA2 mutation based on ethnicity and personal and family history of cancer, and finds her risk to be 31%. In view of this risk, genetic testing for BRCA1 and BRCA2 is offered after a detailed discussion of the genetic differential diagnosis, the implications of a positive vs a negative test result, the possibility of finding gene changes (variants) of unknown significance, and the implications of the test results for family members.
Your patient elects to pursue BRCA1 and BRCA2 genetic testing and the results are negative—no mutations in either gene are found. PTEN testing is recommended next, which your patient elects to undergo. A mutation in the PTEN gene is found, indicating that she has Cowden syndrome. This result and its implications are discussed in a posttest genetic counseling session.
Cowden syndrome is an autosomal-dominant condition that carries a heightened risk of benign and malignant neoplasms, including a lifetime risk of breast cancer of up to 85%, with the average age at diagnosis in the 40s. Mutations in the PTEN gene also predispose to other cancer types, including nonmedullary thyroid, uterine, renal, and colorectal cancers, as well as melanoma.9 Multiple benign skin lesions and gastrointestinal polyposis are common.20
During the appointment, medical management options for patients with PTEN mutations are presented (Table 4).9 Given that your patient’s breast cancer was initially treated with lumpectomy, her remaining breast tissue is at risk of a second malignancy. She has never undergone thyroid imaging, colonoscopy, or kidney imaging. She reports that lately she has had occasional abnormal uterine bleeding and pain, which she believes are caused by her uterine fibroids. Given these symptoms and in light of her PTEN mutation, hysterectomy may be presented to her as an option. The genetics team sends a detailed clinical note directly to the primary care physician so they can coordinate and “quarterback” the patient’s care.
Like many patients, your patient is very concerned about how this information may affect her daughter. She first expresses some guilt at having to tell her daughter that she may have “given” her a risk of cancer. However, during the course of the genetic counseling session, she accepts that she could not have prevented her daughter from possibly inheriting this mutation, and understands that sharing this information will enable her daughter to pursue testing to help her understand her own risks.
When a known mutation exists in the family, as is the case with your patient, predictive testing only for that mutation gives a 100% accurate result. During a separate genetic counseling appointment, the patient’s daughter opts to proceed with testing and is found to be negative for her mother’s PTEN mutation.
