Celebrities often set trends: they show us what to wear, create hairstyles, and inspire tattoos. But when it comes to your health it is important to know the facts before joining a trend. This blog explains our current scientific knowledge of BRCA inherited mutations that increase breast cancer risk.
It has been published that Jolie carries a BRCA1 mutation and that she has had a double prophylactic mastectomy to reduce the chance of getting cancer. The BRCA1 and BRCA2 genes are known as tumor suppressor genes. Tumor suppressor genes produce proteins that play a role in protecting the body against cancer. BRCA1 and BRCA2 are involved in DNA repair, an important self-defense mechanism to prevent mutations -- the underlying cause of cancer. So if BRCA1 and 2 become faulty because of mutation and cannot carry out its function, the body's defense system against mutations is compromised. This leads to an increased risk of breast and ovarian cancer.
The genetics
We inherit two copies of genes from our parents: one copy from our mother and one from our father. In many cases, both copies of a tumor suppressor gene need to be mutated for the development of cancer. Inheriting one mutated copy of a tumor suppressor gene leads to an increased risk of developing cancer. These patients have a "head start" in a race that no one wants to win. Note that an inherited mutation is present in all of the cells in the body because it was present in either the egg or the sperm before you were conceived. A second "hit" or acquisition of a mutation in the other copy of the gene later in life leads to cancer. This occurs in a single cell of the body. Lifestyle contributes to the risk of getting the second "hit." Inheriting a BRCA mutation leads to an increased risk of breast and ovarian cancer; not all women with one BRCA mutation will develop breast cancer.
The risks
This is the subject that can cause the most confusion and is often incorrectly communicated. In simple terms: about 12 percent (12 women out of 100) will develop breast cancer over their lifetime [1]. The lifetime risk of breast cancer rises to 60 percent (60 out of 100) if a woman has inherited a harmful mutation in BRCA1 or BRCA2. Note that these are risks of getting breast cancer and not dying from it; the arsenal of drugs to treat breast cancer has expanded in recent years and as reported in the National Cancer Institute (2012) Cancer Trends Progress Report, the trend in death rates from breast cancer is falling. It is estimated that 5-10 percent of breast cancers are due to mutations in BRCA genes.
Possible choices
There are several possible choices for reacting to a positive genetic test that increases the risk of breast cancer. Jolie has taken the most radical option -- she has chosen to have a double prophylactic mastectomy. This is still no guarantee because this procedure cannot remove all at-risk tissue.
Keeping a watchful eye by increasing cancer screening is another option for women who have an inherited BRCA mutation. The American Cancer Society recommends that women at high risk should get a mammogram and magnetic resonance imaging (MRI) scan every year and that women with BRCA gene mutations should begin this screening at age 30. Currently, 61 percent of breast cancers are diagnosed at a localized stage, for which the five-year survival rate is 98 percent.
Chemoprevention is another approach. This is the use of natural or synthetic agents to prevent, stop, or reverse the development of cancer. Tamoxifen, a drug that was the gold-standard treatment of breast cancer for decades, has also been approved by the U.S. Food and drug Administration (FDA) for breast cancer risk reduction. Some studies have shown that it may be able to help lower the risk of breast cancer in those carrying BRCA mutations. Raloxifene is another chemopreventative drug against breast cancer approved by the FDA.
Adopting evidence-based recommendations for lifestyle choices to reduce risk is important for all (note the emphasis on evidence-based). The Food, Nutrition, Physical Activity, and Prevention of Cancer report published by the American Institute for Cancer Research and World Cancer Research Fund makes 10 general recommendations for the prevention of cancer. This list includes maintaining a healthy weight, engaging in physical activity, and limiting alcohol consumption. Factors that increase lifetime exposure to estrogen are known risk factors for breast cancer that should be avoided when possible.
There is always something in the pipeline
There is always something in the pipeline -- something new always in development. One new approach on the horizon for treating patients with BRCA mutations uses molecular partners to create a deadly combination in cancer cells in these patients, and not healthy cells. The agent, called olaparib, which targets a DNA repair pathway needed in BRCA deficient cells, is used to create the deadly combination. Encouraging results from early-phase clinical trials that use this "synthetic lethal" approach have been reported in the New England Journal of Medicine. Science continues to be the underlying reason why millions survive cancer.