According to current estimates for the year 2009, 192,370 women and 1,910 men will develop breast cancer,1 and 21,550 women will develop ovarian cancer.2 BRCA1 and BRCA2 gene mutations are responsible for 5% to 10% of these cancers.3-5
ABOUT BRCA1 AND BRCA2
Everyone has the BRCA1 and BRCA2 genes. A mutation in either gene increases the risk of certain cancers. In women, a mutated BRCA increases the risk of breast and ovarian cancer.3 In men, a BRCA mutation increases the risk of breast and prostate cancer.3 Although much less common, mutations in BRCA2 may increase a patient's risk of lymphoma, melanoma, and cancers of the pancreas, gallbladder, bile duct, and stomach.3,4,6 A mutated gene is autosomal dominant and may be inherited from the patient's mother or father.3-5, 7
In the general population, 12% of women are likely to develop breast cancer and 1.4% of women will develop ovarian cancer.3 If a woman has a BRCA mutation, her risk of breast cancer is five times that of a woman without the mutation, or 60%, and the risk of ovarian cancer in a woman with the mutated gene is 15% to 40%.3
GROUPS AT HIGH RISK
Certain ethnic groups, such as people of Ashkenazi Jewish, Norwegian, Dutch, French Canadian, or Icelandic descent, have a higher predisposition toward cancers caused by a BRCA gene mutation.3,4,7,8 Patients with a strong family history of certain cancers are also likely to be carriers of BRCA1 or BRCA2 mutations and should be tested.5,7,8 These groups include those with a
• Personal history of breast cancer before age 50
• Personal history of two primary breast cancers
• Personal history of both breast and ovarian cancer
• Family history of a male breast cancer
• Family history of breast cancer before age 50
• Family history of breast or ovarian cancer in more than one relative
• Family history of both breast and ovarian cancer in one relative
• Known BRCA1 or BRCA2 mutation in the family.
TESTING FOR A BRCA MUTATION
If a patient wishing to be tested for a BRCA mutation has a family history (as opposed to a personal history) of cancer, the sensible approach is to first test the relative who has been diagnosed with breast or ovarian cancer.4,7 The cost of testing is typically covered by health insurance for patients with known or approved risk factors. If insurance does not cover the cost of the test or the patient does not have the appropriate risk factors, the out-ofpocket expenditure can be as much as a few thousand dollars.
MANAGEMENT OF BRCA CARRIERS
In women with a BRCA mutation, prophylactic mastectomy reduces the risk of breast cancer by 90%, and prophylactic salpingo-oophorectomy reduces the risk of ovarian and breast cancer by 90% and 50%, respectively.8 For women who choose not to undergo these procedures, close follow-up is recommended. Mammography and/or breast MRI should be done every 6 to 12 months, a clinical breast examination should be performed every 6 months, and breast self-exams should be done monthly (to detect breast cancer as early as possible).3,7,8 There is controversy regarding the use and effectiveness of tamoxifen (Nolvadex, generics) and raloxifene (Evista) in the prevention of BRCArelated breast cancer.3,8 Surveillance for ovarian cancer includes an annual or biannual clinical examination, transvaginal ultrasonography, and measurement of cancer antigen (CA) 125.3,7,8
Men with BRCA gene mutations should also be followed more closely. Prostate cancer screening should begin between ages 40 and 50 and includes a prostate examination and PSA determinations.4 Because these men are also at an increased risk of developing breast cancer, clinical examinations and mammography should be performed.4
A patient with a negative BRCA result on testing has the same risk for developing cancer as the general population.3,7,8 JAPPA
Jill Gore is a PA with Cancer Care Centers of South Texas in San Antonio. She has indicated no relationships to disclose relating to the content of this article.
Mary Hewett, MS, PA-C, department editor
REFERENCES
1. Breast cancer. National Cancer Institute Web site. http://www.cancer.gov/cancertopics/types/breast. Accessed August 7, 2009.
2. Ovarian cancer. National Cancer Institute Web site. http://www.cancer.gov/cancertopics/types/ovarian. Accessed August 7, 2009.
3. BRCA1 and BRCA2: cancer risk and genetic testing. National Cancer Institute Web site. http://www.cancer.gov/cancertopics/factsheet/risk/brca. Updated May 29, 2009. Accessed August 7, 2009.
4. Breast/ovarian cancer: BRCA1 & BRCA2. Memorial Sloan- Kettering Cancer Center Web site. http://www.mskcc.org/mskcc/html/8623.cfm. Updated January 5, 2009. Accessed August 7, 2009.
5. Fact sheet on genetic testing for breast and ovarian cancer susceptibility. Office of Public Health Genomics Web site. http://www.cdc.gov/genomics/resources/diseases/breast_ovarian_cancer.htm. Updated July 21, 2009. Accessed August 7, 2009.
6. BRCA-1 and BRCA-2. Lab Tests Online Web site. http://www.labtestsonline.org/understanding/analytes/brca/multiprint.html. Updated July 29, 2009. Accessed August 7, 2009.
7. BRCA genetic testing for patients with and without breast cancer. The American Society of Breast Surgeons Web site. http://www.breastsurgeons.org/statements/brca.php. June 12, 2006. Accessed August 7, 2009.
8. BRCA gene test for breast cancer. Mayo Clinic Web site. http://www.mayoclinic.com/health/brca-gene-test/my00322. December 3, 2008. Accessed August 7, 2009.