Management Options for Women with BRCA Mutations
There are three basic approaches to management of cancer risk in women who have germline BRCA1 or BRCA2 mutations. These three approaches include increased surveillance, use of chemopreventive medications, and prophylactic surgery. Consideration of these options is important not only for women who do not have cancer, but also for those who have been diagnosed with hereditary breast cancer, and are therefore at higher risk of developing a second cancer of the breast or ovary.
Surveillance for Breast Cancer
Treatment outcomes are greatly improved when breast cancer is detected early and thus guidelines to detect breast cancer early in those at high risk include:
- Monthly self breast examination, beginning at age 18 to 21
- Annual or semi-annual clinical breast examination, beginning at age 25 to 35
- Annual mammography beginning between ages 25 to 35
Clinicians should encourage and teach the technique of self-breast examination starting in young adulthood because of the earlier onset of breast cancer in women with inherited mutations. Clinical breast examination is also important, especially in young women whose dense breast tissue can make mammograms hard to interpret.
Some concern has been raised that repeated low doses of radiation from mammography might promote breast cancer in women with BRCA mutations. Recent studies of radiotherapy to treat breast cancer in women with BRCA mutations have provided reassurance that this risk is hypothetical and are outweighed by mammography's benefits in terms of early detection.
Surveillance for Ovarian Cancer
Recommendations for ovarian cancer surveillance in women with BRCA mutations include annual or semiannual surveillance with transvaginal ultrasound and serum CA-125 levels, beginning between the ages of 25 and 35. The use of color flow Doppler imaging may enhance the sensitivity of detecting an ovarian cancer. The timing of ultrasound is important, as those ultrasounds performed during the early follicular phase of the menstrual cycle are less likely to pick up normal functional changes that may be falsely interpreted as an abnormality. In addition, CA-125 levels have been known to be elevated in women with a variety of benign conditions and thus are not specific for the presence, or absence of ovarian cancer. Women should be counseled that there is no evidence that this approach is effective, but that at the current time, these are the best tools that we have for the surveillance of ovarian cancer in those at high risk.
Chemoprevention of Breast Cancer
Chemoprevention may be implemented in conjunction with increased surveillance. Findings from the National Surgical Adjuvant Breast and Bowel Project demonstrated that tamoxifen reduced the incidence of estrogen receptor positive breast cancer by almost half in those women who were calculated to be at high risk of the disease. Studies are underway to determine if tamoxifen and other SERMS may be useful as chemopreventive agents in those at high risk of breast cancer.
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Chemoprevention of Ovarian Cancer
The benefits of oral contraceptives in reducing ovarian cancer risk in the general population appear to extend to women with BRCA mutations. Controversy exists over the possible increase in breast cancer risk in women who have taken oral contraceptives. In some of the earlier studies, many of these women received oral contraceptives before the availability of current low-dose formulations containing less than 50 mcg of estrogen. Careful monitoring of women with BRCA mutations who use oral contraceptives is advised.
Prophylactic Mastectomy
Prophylactic bilateral mastectomy has been shown to reduce the risk of breast cancer by 90% in women who have a family history of disease and has shown similar efficacy in women with BRCA mutations. In a study of high-risk women who choose this procedure, the majority (74%) reported diminished emotional concern about developing breast cancer (JAMA 2000; 284:319-24.) Most women reported no changes, or even favorable effects, on levels of emotional stability, stress, self-esteem, and sexual relations.
Women who are contemplating prophylactic mastectomy should see an experienced surgical specialist. Total mastectomy (removal of the breast tissue and the nipple/areolar complex) is preferred as this procedure removes more breast tissue than subcutaneous mastectomy. Advanced techniques for breast and nipple reconstruction are available and are based upon a woman's individual body type and preference.
Prophylactic Oophorectomy
Because early detection of ovarian cancer remains difficult, bilateral prophylactic salpingo-oophorectomy (fallopian tube and ovary) is generally recommended once a woman has completed childbearing or has reached her mid to late 30's. In many women, this procedure can be performed laparoscopically with minimal morbidity. Data suggests that prophylactic salpingo-oophorectomy reduces the risk of ovarian cancer by 95% in women with BRCA mutations. In addition, data suggest that prophylactic oophorectomy may also reduce the risk of breast cancer by 50% in women who have the procedure performed in their 30's or early 40's. Significantly, this reduced risk of breast cancer was observed even in women who received hormone replacement therapy (HRT) following prophylactic oophorectomy. This may be because the amount of hormone given in HRT is generally less than that produced by the ovaries normally.
An issue that commonly arises is when to consider total abdominal hysterectomy in a woman who plans to undergo prophylactic oophorectomy. If a woman wants to take tamoxifen, then removing her uterus can eliminate concern about this drug's stimulatory effects on the endometrium by preventing not only the relatively small risk of endometrial cancer but also uterine polyps and bleeding, which are more common and frequently troublesome. These benefits are worth discussing with women who are contemplating prophylactic oophorectomy.
Quality of Life Issues in BRCA Carriers
It is our belief that women benefit from an the opportunity of counseling and education, before and after testing to help them understand the risks, benefits and limitations of genetic testing and of the various management options that are available to them. One of the goals of post-test counseling is to ensure that the information is used to improve healthcare. Management plans are devised individually - such that they take into consideration not only mutation status, bur lifestyle, overall health, and quality of life issues. Our goal is to assist in the process and provide education and guidance for individuals making these important choices. The key to remember is that - every woman is different and has different psychosocial concerns - we must individualize management to match her particular symptoms, risk factors, and preferences.
Cancer Detection and Risk Reduction Options for Woman with BRCA Mutations
Increased Surveillance:
- Monthly breast self-examination starting at age 18 to 21
- Annual or semi-annual clinical breast exams beginning at age 25-35
- Yearly mammography beginning between ages 25 to 35
- Annual or semiannual transvaginal ultrasound and testing for CA-125 to detect ovarian cancer beginning between the ages of 25 to 35
Chemoprevention:
- Drugs such as tamoxifen greatly reduce the risk of breast cancer in high-risk women
- Oral contraceptives have been associated with a 50% to 60% reduction in the risk of ovarian cancer in women with BRCA mutations
Prophylactic Surgery:
- Preventive mastectomy significantly reduces the risk of breast cancer in women with BRCA mutations
- Preventive removal of the ovaries reduces the risk of ovarian cancer, and also breast cancer, in women with BRCA mutations
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