BRCA1 and BRCA2 mutations: when your genes increase your cancer risk


By Laurén A. Doamekpor, MPH
2014

 

When Angelina Jolie announced that she had removed both of her healthy breasts to reduce her risk of breast cancer, she explained that she had inherited the BRCA1 gene mutation, which increases her chances of someday developing breast cancer. This is why she decided to have a preventive (or prophylactic) double mastectomy. Angelina’s public decision drew attention to women with BRCA1 and BRCA2 mutations and the choices they make. Click here to read our response to Angelina’s double mastectomy, published in the Huffington Post.

BRCA1 and BRCA2 gene mutations also increase a woman’s chances of having ovarian cancer. Ms. Jolie has not yet had her ovaries removed. 

What are BRCA1 and BRCA2?

BRCA1 and BRCA2 are human genes that produce proteins that suppress tumors and repair damage to our DNA. If there is a mutation in one of these genes and they do not work properly, DNA damage may not be repaired. This can eventually cause cancer.

If you have a BRCA1 or BRCA2 mutation, what are the chances of getting breast or ovarian cancer?

Women who have no family history of breast cancer and don’t carry the BRCA1 or 2 gene mutation, have only a 12% chance of getting breast cancer in their lifetime.1 But women with BRCA1 have about a 55% to 65% chance of developing it by the time they turn 70; the likelihood is a little lower for women with BRCA2 at 45%.2 3

Even though women with BRCA1 or BRCA2 are about 5 times more likely to get breast cancer than the average woman, women with these mutations make up only 5% to 10% of all breast cancer cases. In other words, fewer than 1 in 10 women with breast cancer have either BRCA1 or BRCA2.4

Ovarian cancer is less common than breast cancer. Fewer than 2% of women who have neither BRCA1 or BRCA2, nor a family history of ovarian cancer, will develop ovarian cancer. But, 39% of women with BRCA1 will develop ovarian cancer by age 70, and approximately 11%-17% with BRCA2 will develop ovarian cancer by 70.2 3

Doctors will often suggest testing for the BRCA1 and BRCA2 genes in women with family members diagnosed with breast or ovarian cancer before age 50, family members with cancer in both breasts or multiple breast cancers, and women who come from Ashkenazi Jewish backgrounds.

If you have BRCA1 and BRCA2, what can you do to lower your risk for breast or ovarian cancer?

If you find out that you have the BRCA1 or BRCA2 mutation, it doesn’t mean you will definitely get breast or ovarian cancer.

There are a few ways you can lower your risk of breast cancer:

1) More frequent breast exams to detect cancer as early as possible. Some experts recommend that women with BRCA1 or BRCA2 begin breast cancer screening as early as age 25 4, but that doesn’t mean mammograms should start at such an early age. Young women with BRCA mutations should get screened using magnetic resonance imaging (MRI). MRIs are more accurate than mammograms for young women and do not expose breasts to as much radiation as mammograms do. While early screening can be helpful, if a woman’s genes place her at higher risk, she needs to realize that regular radiation to the breasts at an early age could increase her risk of cancer.

2) Take an estrogen-blocking pill such as tamoxifen. Many breast cancers feed off the estrogen produced naturally by a woman’s body so interrupting the production and flow of estrogen can reduce a woman’s risk of getting breast cancer. Taking tamoxifen after being treated for breast cancer, for instance, usually cuts the risk of breast cancer recurring by about half. However, the effectiveness of raloxifene or tamoxifen in women with BRCA1 and BRCA2 has not been studied specifically yet. 4

3) Preventive mastectomy (removal of the breasts). When a woman with BRCA1 or BRCA2 gets both of her breasts surgically removed, she reduces her chances of getting breast cancer by as much as 95%.5 Why is there still some risk? Because some breast tissue is left behind after surgery, and cancer can develop in that tissue or on the nearby chest wall.6

4) The removal of both ovaries and the fallopian tubes, called salpingo-oophorectomy. The ovaries produce estrogen which make the more common breast cancers more likely to grow, so removing the ovaries and fallopian tubes works much like tamoxifen. Research shows that women with BRCA1 or BRCA2 can reduce their breast cancer risk up to 50% by removing just their ovaries. 5 Removing the ovaries and fallopian tubes is the only known method of reducing the risk of ovarian cancer.

What about having children? While having children reduces the chances of developing the most common types of breast cancer, research published in 2014 found that women with BRCA1 or BRCA2 mutations who decide not to have children are no more likely to develop breast cancer than women with the mutations who do have children. For women with BRCA1 who want to have children, it’s helpful to know waiting until after 30 to have a child and breastfeeding longer—for at least 1-2 years—seems to lower their risk of breast cancer. Delayed childbearing and longer breastfeeding did nothing to lower breast cancer risk among women with BRCA2, however.7

Maintaining a healthy weight and exercising regularly can reduce the chances of breast and ovarian cancer. For women with BRCA1 or BRCA2, some studies show that women who were overweight (BMI>25) at age 18 and lose at least 10 lbs between age 18 and 30 are less likely to develop early-onset breast cancers.8

What women with BRCA 1 and BRCA2 can do to reduce their risk of ovarian cancer

Other than getting a salpingo—oophorectomy (removing the ovaries and fallopian tubes), which can reduce a woman’s risk of ovarian cancer by 90% 9, there is little else a woman with BRCA mutations can do to lower her risk of ovarian cancer. Even after having her ovaries removed, a woman with BRCA mutations will still have a small chance of getting ovarian cancer in the peritoneum (a thin layer of tissue that lines the inside of the abdomen). This can happen if some ovarian tissue is left behind after surgery or if ovarian cancer cells have already spread to that part of the body before surgery.10

The drawback to getting your ovaries and fallopian tubes surgically removed is that you won’t be able to have children naturally and will have to adopt or use some form of assisted reproductive technology like IVF with frozen embryos or frozen eggs. Moreover, studies show that women who have had their ovaries removed are more likely to suffer heart disease, stroke, lung cancer, and depression or anxiety disorders. And the risk of these illnesses is higher the younger the woman is when her ovaries are taken out. Also, if a woman has her ovaries removed before going through menopause, the surgery will cause a sudden drop in estrogen and bring on early menopause.11

There is no widely accepted screening to detect ovarian cancer early. In fact, the U.S Preventative Services Tasks Force recommends against yearly screenings for ovarian cancer in women except those with BRCA1, BRCA2 or a family history of ovarian cancer. Some medical groups recommend transvaginal ultrasound examinations and the CA-125 blood test.  But research shows that these screening tools are not very accurate and do not reduce a woman’s chances of dying from ovarian cancer.

Bottom Line

For any woman—whether she is a BRCA carrier or not–maintaining a healthy weight and exercising regularly can reduce the chances of breast and ovarian cancer. You can learn more about ovarian cancer here and more about the risks and benefits of preventive mastectomies to reduce the risk of breast cancer here.

There are other ways women with BRCA1 or BRCA2 mutations can lower their risk of breast and ovarian cancer, such as screening to detect cancer early, surgery to remove breasts, ovaries, and fallopian tubes, estrogen-blocking drugs, and losing weight if they are overweight. While screening regularly for breast cancer with MRIs is safe, surgery and drugs have side effects and risks. Women with the BRCA mutations will want to consult with several different doctors to discuss what is important to them at each phase of their reproductive lives, and weigh the risks and benefits of each prevention strategy.

  1. Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies. American Journal of Human Genetics 2003; 72(5):1117–1130  
  2. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of Clinical Oncology 2007; 25(11):1329–1333  
  3. The Centers for Disease Control and Prevention. http://www.cdc.gov/features/hereditarycancer  
  4. National Cancer Institute. http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA  
  5. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967-75.  
  6. Office on Women’s Health. U.S. Department of Health and Human Services. https://www.womenshealth.gov/publications/our-publications/fact-sheet/early-stage-breast-cancer.html#g  
  7. Pan H, He A, Ling L, et al. Reproductive factors and breast cancer risk among BRCA1 or BRCA2 mutation carriers: Results from ten studies. Cancer Epidemiology. 2014;38:1-8.  
  8. Kotsopoulos J, Olopado OI, Ghadirian P, et al. Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 2005;7:R833 – 43.  
  9. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/prevention/ovarian/HealthProfessional  
  10. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/prevention/ovarian/Patient/page3  
  11. Kauff ND, Satagopan JM, Robson ME, et al. Risk reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346:1609-1615.