BRCA1 and BRCA2: Cancer Risk and Genetic Testing
All individuals have genes, which are small pieces of instruction inherited from either mother or father. BRCA1 and BRCA2 belong to classes of genes know as tumor suppressors. If they change (mutate) they cannot control the risk of ovarian and breast cancer. Each child of a genetic carrier, regardless of sex, has a 50% chance of inheriting the mutated gene from the parent who carries the mutation.
The ovarian cancer lifetime risk in a carrier with a BRCA1 mutation is 45% and a BRCA2 is 25% (general population 8%). The lifetime risk of breast cancer with BRCA1 is 65-85% and BRCA2 is 45-85% (general population 0.7%). In the general population, Ashkenazi Jews and Icelandic people have a significant risk of 2-3% mutation of BRCA1 and BRCA2.
To decide if you should receive genetic counseling and be tested for BRCA1 or BRCA2 mutation - the following are some of the clinical indicators:
Testing a family member who has ovarian or breast cancer to see if that person has BRCA1 or BRCA2 mutation.
For women who are not of Ashkenazi Jewish descent:
Two first-degree relatives (mother, daughter, or sister) diagnosed with breast cancer, one of whom was diagnosed at age 50 or younger
Three or more first-degree or second-degree (grandmother or aunt) relatives diagnosed with breast cancer regardless of their age at diagnosis
A combination of first and second-degree relatives diagnosed with breast cancer and ovarian cancer (one cancer type per person)
A first-degree relative with cancer diagnosed in both breasts (bilateral breast cancer)
Combination of two or more first or second-degree relatives diagnosed with ovarian cancer regardless of age at diagnosis
First or second-degree relative diagnosed with both breast and ovarian cancer regardless of age at diagnosis
Breast cancer diagnosed in a male relative
For women of Ashkenazi Jewish descent:
Any first-degree relative or second-degree relatives diagnosed with breast or ovarian cancer.
Management of a person who has a positive test results
Women below the age of 35:
As women age into menopause the risk of epithelial ovarian cancer increases. In young women with a positive test result - surveillance can be recommended. A gynecologic oncologist is the best person to carry out the surveillance.
For ovarian cancer, surveillance should be done every 6 months, and includes careful history and physical exam, transvaginal ultrasound, and blood test for CA 125.
If the CA 125 is over 35/ml this should be repeated in 4 to 6 weeks. A statistical rise requires evaluation usually with laparoscopy.
A careful history of possible symptoms of ovarian cancer should be noted. These can be vague and not gynecologic. These symptoms include bloating, pelvic or abdominal pain difficulty eating or feeling full quickly and urinary urgency or frequency. Oral-contraceptive used reduces the risk of ovarian cancer among women who carry the mutation of BRCA1 or BRCA2. This can be used until a women desires to become pregnant.
Women who have completed child bearing or are over 35 years of age
It is recommended that risk-reduction salpingo-oophorectomy be carried out in carriers of BRCA mutations who have completed childbearing. It is important that the tube as well as the ovaries be removed. Tubal sterilization and/or oral contraceptivescan reduce, but salpingo-oophorectomy has the greatest risk reduction. Peritoneal cancer continues as a risk after salpingo-oophorectomy.
For more information about BRCA1 and BRCA2 we recommend you visit the National Cancer Institute at: http://www.cancer.gov/
ROBERT C. KNAPP, MD, D.Sc (Honorary)
Board Member and Chairman of the Medical Advisory Board
William Baker Professor of Gynecology (Emeritus), Harvard Medical School
Visiting Scholar, Weill Medical College of Cornell University
Former Director of Gynecology, Brigham & Women’s Hospital
Former Director of Gynecology Dana Farber Cancer Center
To learn more about ovarian cancer, click HERE