Genetic Risk Factors for Breast Cancer
- Genetics Overview
- How do physicians test for BRCA mutations?
- Who should consider genetic testing?
- Preventing breast cancer in BRCA-positive women
|Breast Cancer Prevention
Women who test positive for BRCA1 or BRCA2 genetic mutations are at higher risk of developing breast cancer and may wish to consider preventive measures. The Mayo Clinic suggests that women at increased cancer risk limit alcohol consumption and exercise regularly. Additionally, increased breast screening helps to detect breast cancer at an early stage (when it is more easily treatable).
The American Cancer Society suggests the following guidelines to help detect breast cancer early:
- Women 20 years of age and older should perform breast self-examination (BSE) every month.
- Women 20-39 should have a physical examination of the breast (CBE or clinical breast exam) at least every three years, performed by health care professional such as a physician, physician assistant, nurse, or nurse practitioner. CBE may often be received in the same appointment as a Pap smear. Women 20-39 should also perform monthly BSE.
- Women 40 and older should have a physical examination of the breast (CBE or clinical breast exam) every year. CBE should be performed by a health care professional such as a physician, physician assistant, nurse, or nurse practitioner. CBE can often be performed in the same visit as a mammogram. Monthly BSE should also be performed.
- Women 40 years of age and older should have a screening mammogram every year in addition to annual CBE and monthly BSE.
Women at high risk of developing breast cancer (in consultation with her physician) may begin screening mammography earlier age 40. Some experts suggest beginning screening ten years prior to the age at which a close relative (mother, sister) was diagnosed with breast cancer.
"Chemoprevention" (the use of drugs, chemicals, vitamins, or minerals to treat breast cancer) is another option for women at increased risk of developing breast cancer. One type of chemoprevention involves the anti-cancer drug, tamoxifen. Tamoxifen has been used for twenty years to treat advanced breast cancer. More recently, tamoxifen has been used to treat early-stage breast cancer and to lower the risk of breast cancer in women who are at high risk for the disease.
In its first major breast cancer prevention trial (BCPT) from April 1992 to 1998, researchers for the National Surgical Adjuvant Breast and Bowel Project (NSABP) found a 49% decrease in the incidence of invasive breast cancer in women at increased risk for the disease who took tamoxifen therapy in comparison to those who did not receive the drug and received a placebo (an inactive pill) instead. The study showed that women taking tamoxifen also had fewer diagnoses of noninvasive breast cancer, such as ductal carcinoma in situ (DCIS). Click here for more information on the NSABP tamoxifen trials.
Some women at high risk of developing breast cancer may choose to have prophylactic mastectomy (preventive removal of the breasts). A recent study published in the Journal of Medicine revealed that prophylactic mastectomy reduced the risk of breast cancer by 90% in women at high risk for the disease. (Prophylactic mastectomy cannot reduce breast cancer risk by 100% because it is not possible to remove all of the breast tissue). The mortality rate from breast cancer was also reduced by 80% in the study.
Researchers are still not certain how women will be affected by prophylactic mastectomy, though. Preventive surgery may increase life expectancy in women with aggressive tumors. However, other women with BRCA1 or BRCA2 mutations never develop breast cancer and thus do not benefit from prophylactic mastectomy. Less invasive procedures (such as lumpectomy) may also be performed to treat breast cancer without having to remove the breast(s).
Though medical experts still do not recommend prophylactic mastectomy, the following women are candidates for the procedure:
- Mutated BRCA1 or BRCA2 genes
- Previous cancer in one breast
- Strong family history of breast cancer (mother or sister had breast cancer)
- Biopsy revealing lobular carcinoma in situ (LCIS)
Note: Women who do not have any of the above conditions should normally not consider having prophylactic mastectomy.
HER2 (human epidermal growth factor receptor 2) is another gene found on the surface of cells that plays a key role in regulating cell growth. When the HER2 gene is altered, extra HER2 receptors may be produced. This over-expression of HER2 causes increased cell growth and reproduction, often resulting in more aggressive tumor cells.
HER2 protein over-expression affects 25% to 30% of breast cancer patients. Women with HER2 over-expression may not be as responsive to standard breast cancer treatments, including certain regimens of chemotherapy.
The United States Food and Drug Administration (FDA) recently approved the drug Herceptin (generic name Trastuzumab) for use in breast cancer patients whose cancer has metastasized (spread) beyond the breast and underarm lymph nodes. Herceptin has been shown to slow the growth and spread of cancerous tumors in a number of clinical trials. In some cases, cancerous tumors have completely disappeared in patients taking Herceptin. Presently, only women who are HER2 positive (and have metastasized breast cancer) are candidates for treatment with herceptin. Click here for more information on Herceptin and HER2.
Little is known about the p53 tumor suppressor except that, when mutated, the p53 gene also increases a woman's risk of developing breast cancer. A recent study published in the conducted by Dr. Ayman Linjawi of the Royal Victoria Hospital in Montreal, Quebec, Canada reveals that women with early-stage breast cancer who test positive for the mutated p53 tumor suppressor tend to have a poorer breast cancer prognosis than women who do not carry the mutated p53. Dr. Linjawi and colleagues found that the Stage I breast cancer patients with the mutant p53 had an average survival rate of 74% after five years compared with a survival rate of 83% who did not have the mutant p53. p53 mutation testing is available to high-risk women at specialized centers. However, according to the American Cancer Society, this testing has not been shown to be helpful in determining current patients' treatment at this point. Further research on p53 genetic testing is needed to determine whether it may one day have value in helping physicians choose a breast cancer patient's best course of treatment.
- (1) The Mayo Clinic offers information on BRCA gene mutations and genetic testing at http://www.mayohealth.org
- (2) The American Cancer Society provides information on genetic risk factors for breast cancer at http//:www.cancer.org
- For additional information on risk factors for breast cancer, please visit http://www.imaginis.com/breasthealth/bc_risks.asp.
- To learn more about HER2 and herceptin, please visit http://www.imaginis.com/breasthealth/herceptin.asp.
- For a complete list of "Chemicals Known to [California] State to Cause Cancer," please visit the Office of Environmental Health Hazard Assessment webpage at http://www.oehha.org/home.html
- Informed Medical Decisions provides risk assessment and informed medical decision-making based on family history.
- To learn more about candidates for BRCA gene testing, please visit http://www.imaginis.com/breasthealth/BRCA.asp
Updated: December 2011