November 2009 A SUPPLEMENT TO Risk Assessment and Management of Women With BRCA Mutations Kevin S. Hughes, MD, FACS; Veronica Ravnikar, MD, FACOG D uring a routine visit, a the general population carry a young single mother mutation in BRCA1 or BRCA2.1 uidelines from ACOG tells you that her sister An estimated 1 in 40 people of encourage ObGyns was just diagnosed with breast Ashkenazi Jewish descent have a cancer. A new postmenopausal mutation.1 The estimated lifeto provide breast and patient reveals that her mother time risk for breast cancer in ovarian cancer risk had breast cancer. These are women with a BRCA1 or BRCA2 assessment as part of common scenarios in ObGyn mutation is 65% to 74%.1 practice, but do you provide routine clinical practice. follow-up cancer risk assessIdentifying Patients: ment and genetic counseling Clinical Assessment for hereditary breast and ovarian cancer (HBOC)? One of the most challenging aspects of risk assessIf not, you may want to consider that ACOG ment is identifying which patients to test. Not every guidelines encourage ObGyns to do so as part of patient should be tested, but those who need testing routine clinical practice and that the widespread should receive it. Start by taking a full medical and availability of genetic testing makes it easier than family history covering 3 generations (the patient, ever to provide this valuable service.1 her parents, and her grandparents), using a combination of a written questionnaire and personal consulHBOC Patients Are in Your Practice tation. Questions to ask include: Most likely, you have patients with HBOC in •Breast cancer before age 50? your practice who need to be identified. It is •Breast cancer in 2 or more relatives? estimated that about 1 in 300 to 1 in 800 people in •Breast cancer in a male relative? •Breast cancer in both breasts or twice in the same breast? Kevin S. Hughes, MD, FACS, is Surgical Director, •Breast cancer and Ashkenazi ancestry? Breast Screening, and Co-Director, Avon Comprehensive Breast Evaluation Center, Massachusetts General Hospital, •Ovarian cancer at any age? Boston; Veronica Ravnikar, MD, FACOG, is AssociInclude in the history any relevant environmenate Clinical Professor of Obstetrics and Gynecology and tal exposures, risk factors for breast and ovarian Reproductive Medicine, Harvard Medical School, Boston, cancer, and surgeries that may have obscured the and Chair, Department of Obstetrics and Gynecology, South Shore Hospital, South Weymouth, MA. hereditary cancer pedigree. G Supported by an educational grant from Myriad Genetics, Inc. Risk Assessment and Management of Women With BRCA Mutations To assist in identifying potential candidates for testing, ACOG provides a detailed list in the “Criteria for Genetic Risk Assessment” table in its guidelines.1 ACOG recommends genetic testing for patients with a greater than 20% chance of having a BRCA1 or BRCA2 mutation. For women with a 5% to 10% or greater risk, ACOG recommends genetic risk assessment and possible testing.1 Many patients in your practice meet these criteria and need to be identified and counseled. Whether the test results are positive or negative, the information is important and useful to both the patient and the health care professional. Either result leads to informed development of critical patient management strategies. Discussing the Options When a patient falls into a group recommended for testing, it is time to discuss the options. The conversation might begin like this: “I recommend a blood test that is usually covered by insurance that can help you better understand your risk for hereditary breast and ovarian cancer, or HBOC. Knowing your risk can help you take steps to reduce your risk for these conditions. HBOC is most often caused by a mutation, or alteration, in either of 2 genes, BRCA1 and BRCA2. Although the risk for these cancers is high, not everyone with HBOC syndrome will develop cancer. This test can help me care for you better and can help you better care for yourself. Would you like to hear more about this test?” Whether the test results are positive or negative, the information is important and useful to both the patient and the health care professional.2 Either result leads to informed development of critical patient management strategies. Medical management options that should be discussed before testing include an increased surveillance plan, chemoprevention (tamoxifen, oral contraceptives), and risk-reducing surgery (mastectomy, oophorectomy).1 It is important to remember that if the patient does not pursue testing, you and she will still need to develop a more intensive management strategy based on her risk level. Testing can help you The Female Patient Supplement NOVEMBER 2009 both make that strategy more tailored to her actual situation. A simple approach to confirm you have given complete information is to read through and discuss with the patient the “Elements of Informed Consent for Cancer Susceptibility Testing” as they appear in the American Society of Clinical Oncology guidelines.3 It is also helpful to provide her with written information she can share with relatives. Going Forward With Testing Once the decision is made to go forward with testing, it is ideal to initiate testing in an affected person, whether it is the patient or a family member. If an affected person is not available, testing is still beneficial. If you would prefer to refer the patient for testing rather than manage the process yourself, you can identify a risk assessment clinic in your area by going to the National Cancer Institute’s Cancer Genetics Services Directory (www.cancer.gov/search/genetics_services). Risk assessment and genetic counseling can be provided by licensed genetic counselors, medical geneticists, medical oncologists, social workers, surgeons, oncology nurses, nurse practitioners, and/or psychologists.4 Many patients do not follow up with these appointments, however. As the testing information is essential for effectively managing your patients’ health, consider integrating assessment and testing into your practice. Discussion of Test Results Results of HBOC testing are usually available in about 2 weeks. Discussion of test results requires sensitive communications and informed consent. Explain that the test results are disclosed only to you and that federal laws prohibit discrimination against patients who undergo genetic testing. Remind the patient that the test does not detect cancer; it Hughes provides information on inherited risk for cancer. Possible test results are positive, negative, or uninformative. Patients will respond to the results based on their life circumstances, age, and cancer mindset. For example, the young single mother mentioned above may not want to undergo prophylactic surgery, whereas the older woman might welcome it. Of course, refer patients to an appropriate counselor if they have problems with the information. Ideally, all women at risk for HBOC would be identified before cancer develops. Screening and prevention strategies could then be implemented that could potentially save lives. Management of Women With BRCA Mutations Ideally, all women at risk for HBOC would be identified before cancer develops. Screening and prevention strategies could then be implemented that could potentially save lives. In addition to ACOG, the National Cancer Center Network recommends that women be screened for potential mutations.1,4,5 Currently, women learning that they have a BRCA mutation fall into 3 broad categories: unaffected, newly diagnosed with cancer, and diagnosed with cancer in the past. Management options differ for these groups and include screening with or without chemoprevention or risk-reducing surgery. Management should be based on age, overall health, and personal preferences. A critical element is dissemination of risk information to as many family members as possible. Once a carrier is identified, a concerted effort should be made to identify every other carrier in the family. Options for Unaffected Women Breast Surgery. Prophylactic bilateral total mastectomy is the most effective strategy for prevention of breast cancer, offering a 95% reduction in risk. Nipple-sparing mastectomy may be an option and is currently under investigation. Nipple-sparing mastectomy is not to be confused • Ravnikar with subcutaneous mastectomy, which leaves behind a large amount of breast tissue and is not considered acceptable for prophylaxis. Screening With or Without Chemoprevention. For those who opt against prophylactic mastectomy, screening is essential, with or without chemoprevention. Screening should include monthly breast self-examination and, starting at age 25, clinical examinations, annual mammograms, and annual magnetic resonance imaging (MRIs). Tamoxifen has been shown to decrease risk for breast cancer in high-risk women; raloxifene has similar effects but is indicated only for postmenopausal women. Neither has been proved effective in the BRCA carrier population; however, it is reasonable to discuss these in addition to screening. In premenopausal women, prophylactic bilateral salpingo-oophorectomy (BSO) significantly reduces risk for both breast and ovarian cancer. Ovary Surgery. W hereas mastectomy is optional, BSO is essential. As effective screening modalities are not available for ovarian cancer, BSO is strongly recommended after age 35, once childbearing is complete. Screening With or Without Chemoprevention. Twice-yearly transvaginal ultrasound and CA-125 testing should be done starting at age 35 (or earlier if appropriate) until the ovaries are removed. A note of caution: This strategy has unproven efficacy but is still recommended. Oral contraceptives have been demonstrated to reduce risk for ovarian cancer in the general population, as well as in women who carry BRCA mutations. The small potential risk for breast cancer should be considered, though the benefit most likely outweighs the risk. In smokers, morbidly obese women, and women older The Female Patient Supplement November 2009 Risk Assessment and Management of Women With BRCA Mutations than 40, there may be more risk than benefit. There are still Conclusion Discussion of genetic risk and genetic testing is an an inordinate number of Options for Patients integral part of ObGyn Newly Diagnosed clinical care. There is subBRCA carriers who are With Cancer stantial benefit to identifyunaware of their status, The BRCA carrier must choose ing BRCA1 and BRCA2 carmany of whom are cancer between breast conservation riers, as there is a plethora and bilateral mastectomy. Overof management options that survivors. Identification all, while bilateral mastectomy can decrease the morbidity of these women and their is likely the most appropriate and mortality of disease. procedure, it is not proved supeIdentifying carriers and families has substantial rior, and many women are not instituting these strategies benefit and should ready to take this step so soon can be lifesaving. It is critinot be overlooked. after being diagnosed as a carcal to leverage the status of rier. If lumpectomy is chosen, each carrier for the maxiMRI should be done before mal family benefit by testsurgery. If childbearing is complete, oophorectomy ing as many family members as possible. is recommended, as it will markedly decrease the Acknowledgment: The authors would like to risk for ovarian cancer and may have a role as acknowledge Constance Roche, MSN, RN, CS, an adjuvant treatment in premenopausal women for her critical review of this manuscript. with estrogen receptor–positive cancer. The BRCA carrier with newly diagnosed ovarian Disclosures: Dr Hughes is a member of the cancer should undergo a complete course of speakers bureau of Myriad Genetics. Dr therapy and then, based on her prognosis, Ravnikar is a member of the speakers bureau begin a commensurate level of breast screening. and a consultant of Teva Pharmaceuticals. Prophylactic mastectomy should be considered with caution. References Patients Diagnosed With Breast or Ovarian Cancer in the Past There are still an inordinate number of BRCA carriers who are unaware of their status, many of whom are cancer survivors. Identification of these women and their families has substantial benefit and should not be overlooked. Management decisions should be based on cancer history, prognosis, and prior treatment. The patient who has had breast cancer and whose prognosis is good should be managed similarly to the unaffected woman, based on remaining organs. Bilateral mastectomy is appropriate if she prefers. Oophorectomy is suggested once childbearing is complete. Ovarian screening until the ovaries are removed is appropriate. The patient who has had ovarian cancer and whose prognosis is good should be managed similarly to the unaffected woman. The Female Patient Supplement NOVEMBER 2009 1. A merican College of Obstetricians and Gynecologists; ACOG Committee on Practice Bulletins—Gynecology; ACOG Committee on Genetics; Society of Gynecologic Oncologists. ACOG practice bulletin no. 103: hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2009;113(4):957-966. 2. Berliner JL, Fay AM; Practice Issues Subcommittee of the National Society of Genetic Counselors’ Familial Cancer Risk Counseling Special Interest Group. Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2007;16(3):241-260. 3. A merican Society of Clinical Oncology. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol. 2003;21(12): 2397-2406. 4. National Cancer Center Network. Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian. Available at: www.nccn.org/professionals/ physician_gls/PDF/genetics_screening.pdf. Accessed August 8, 2009. 5. Schwartz GF, Hughes KS, Lynch HT, et al. Proceedings of the International Consensus Conference on Breast Cancer Risk, Genetics, & Risk Management, April, 2007. Cancer. 2008;113(10):2627-2637.