Breast Cancer Genetics: Is Testing an Option?

By Mia M. Gaudet, PhD

Certain types of cancer often seem to run in families. Sometimes, it’s because families share certain risk factors (like smoking) that can cause cancer. Other times, though, there is an inherited link – a slight difference in the genetic code that is passed down from generation to generation.


Only about 5% – 10% of all cancers are inherited. It’s an important area of research because identifying genetic causes of cancer could help us understand who might need to be screened for a certain type of cancer more often, or take other steps to protect themselves from this disease. This is the first blog in a series where we’ll explore what researchers have learned about some of the cancers that have a strong genetic link, and who might be candidates for genetic counseling and testing. Today we’ll focus on breast cancer. [more]


Who has increased risk?


Women with 1 or more first-degree relatives (mother, sister, daughter) previously diagnosed with breast cancer have at least double the risk of breast cancer than the general population.  A woman with a family history of breast cancer has a much higher risk of being diagnosed with breast cancer if she has 2 or more first-degree relatives who had it, or the first-degree relative had her cancer before age 50, or in both breasts.  Having a family history of other cancers, such as ovarian cancer, might also lead to an increased risk of breast cancer.


Rare genetic mutations


The increased risk from a family history of breast cancer is explained, in part, by variations in the genes inherited from a woman’s mother, father, or both.  Studies of families with several members with breast cancer and other cancers have led to the discovery of rare genetic variations, known as mutations, which are found in less than 1% of the general population. 


The most common of these mutations are located in two genes named breast cancer gene 1 and breast cancer gene 2 (BRCA1 and BRCA2).  Having mutations in BRCA1 or BRCA2 is also referred to as Hereditary Breast and Ovarian Cancer Syndrome.  These mutations give women a very high lifetime risk of developing breast and ovarian cancers, often times at an early age (younger than 50).  (Males who have BRCA1 and BRCA2 mutations are also at higher risk for prostate and breast cancers.  BRCA2 mutations are also associated with increased risk for pancreatic and stomach cancers and melanoma.)  These mutations are very rare in the general population and slightly more common in certain ethnic groups, such as people of Ashkenazi Jewish descent, and in the Netherlands, Iceland, and Sweden.  


Four other mutations are known that cause hereditary cancer syndromes that lead to a very high risk of breast cancer but they are found in even fewer people in the general population (less than 0.005%).  In addition to breast cancer, families with Cowden Syndrome are also at higher risk of thyroid, endometrial, and renal cancers.  Families with Li-Fraumeni Syndrome, are at higher risk of female breast cancers at a young age as well as brain tumors and sarcomas. Families with Hereditary Diffuse Gastric Cancer are at higher risk of breast cancer and stomach cancer at a young age. Families with Peutz-Jeghers Syndrome are also at a higher risk of breast cancer and are identified by a polyp syndrome in their intestines.   


Together, these 5 syndromes account for about 20% -30% of the families with several cases of breast cancer and less than 10% of breast cancer diagnoses in the general population. 


Current research


Research to find other high-risk mutations that might explain why some families have more breast cancer cases has not been fruitful, suggesting that those mutations do not exist or are very, very rare.  Researchers, instead, have turned their attention to gene changes that are more common but are associated with only minor increases in risk of breast cancer.  Explaining these gene changes might help us understand how genes play a role in the breast cancer risk. However, it will be a long time before it is clear whether these more common gene changes can help us distinguish low-risk women from high-risk women in the general population.  



Who should go for genetic testing?


It is important to know that most women don’t have a family history of breast cancer, and for women who are diagnosed with breast cancer, only a small percentage of them had a family history of breast cancer.


Currently, we don’t recommend genetic testing for these common gene changes because we don’t know enough about them to reliably predict a woman’s risk of breast cancer. Although direct-to-consumer genetic tests are available on the market, genetic testing should never be considered without the advice of your family doctor.


Because mutations that cause hereditary breast cancer are so rare, geneticists don’t think the general population needs widespread screening. Women with multiple relatives with breast cancer or other cancers, or with relatives with breast cancer at a young age, should speak first with their family doctor. The family doctor may refer some women with a strong family history of cancer to a genetic counselor, who can help them decide if genetic testing is right for them. Genetic counselors also help people concerned about their family history to understand the risk and benefits of genetic testing.  


Breast cancer prevention


Women who do undergo genetic testing and find out that they have a mutation that gives them a very high risk of breast cancer do have options to help lower their risk of breast cancer. One option is removing their breasts (prophylactic mastectomy), or removing their ovaries (prophylactic oophorectomy). Studies suggest that these procedures can decrease the risk of breast cancer considerably for women at very high risk. However, it’s important to note that not all women who choose this surgery would have developed breast cancer, and there is no way to know ahead of time if this surgery will benefit a particular woman. Some women would not benefit from the surgery, but they would still have to deal with its after effects. Women who have a known genetic mutation and are considering this surgery should get a second opinion before deciding.


A less drastic measure for high-risk women is chemoprevention, the use of certain drugs to reduce the risk of cancer. These include tamoxifen, raloxifene, and other drugs. If you’re at high risk, speak to your doctor to learn more because each of these drugs also can have side effects that need to be considered.


Still, no single medicine, procedure, or genetic test can guarantee that you won’t develop breast cancer, since most breast cancers are NOT inherited.  But we do know which behaviors can help reduce your risk of developing breast cancer. The American Cancer Society recommends:

  • Getting regular, intentional physical activity
  • Minimizing lifetime weight gain by eating and drinking fewer calories and getting regular physical activity
  • Avoiding or limiting intake of alcoholic beverages

Gaudet is director of genetic epidemiology for the American Cancer Society.

5 thoughts on “Breast Cancer Genetics: Is Testing an Option?

  1. My mother and sister are breast cancer survivors.. Both developed breast cancer after menopause. There are eight women on my maternal side who have been diagnosed with breast cancer. Youngest was 33 at diagnosis. Two were aged 41 and 30’s who are deceased as they were diagnosed so late. The Lance Drye family have four daughters with breast cancer. One was genatically tested as negative. Lance Drye, father of these girls died of prostate cancer.
    My mother will be 95 years old April 9, 2012. I would love to get her tested as it would relieve me regarding myself and my two daughters risk of breast cancer.
    I am under the care of Dr. Kimmy head of the high risk breast cancer program at Scott and White Hospital and Clinic, Temple, Texas. She estimates I have a 1 in 3 chance of developing breast cancer due to my family history. I hate the side effects of tomoxifen, taken as a preventative, concentration problems etc. I wonder if it will contribute to early nursing home placement due to cognitive effects or increased heart problems?
    I was surprised that the first cousin who was genatically tested was negative. Shook my confidence in the testing quality. It must be unusual for 4 sisters to have breast cancer, one deceased,and father died of prostate cancer.

  2. Although I am very sympathetic to women diagnosed with breast cancer as my own mother is a breast cancer survivor. I also lost my father to lung cancer and my grandmother to vulvar cancer. I find the ACS a deplorable organization since we are still in month of August and there has been no mention of Pediatric Cancer. While October has been designated as Breast Cancer Awareness Month, September was designated as Pediatric Cancer Awareness Month and I have yet to hear or see one piece of material the would make ANYONE aware of Pediatric Cancer. The ACS designates 1 cent per dollar of their budget to pediatric cancer. While breast cancer and lung cancer receive the bulk of the budget. I guess the ACS or the public believe that a women's breasts are more important than a childs life. ABSOLUTELY UNACCEPTABLE.

  3. There are several drawbacks to genetic testing. The most obvious is cost and efficiency. Genetic testing is expensive and the results are often difficult to interpret. For example, testing for the BRCA-1 gene is done and is “normal” meaning the person does not have that mutation. This does NOT mean that the person is then free of the risk of developing breast cancer. About 90-95% of breast cancers develop in persons without a familial genetic cancer syndrome. If the test is normal this also means that they still could have another mutation that will lead to early onset breast cancer. There is not a test for every type of genetic mutation that leads to familial cancer also.

  4. Cancer runs in my wife's family (her mother) and we knew that there was a high chance that she could potentially get cancer too…and in fact she did in Oct 2012. It was hard news, but she is beyond amazing. Chemo and surgery is all done and about halfway through radiation. Although genetic testing can be expensive, I completely recommend visiting your doctor more and finding out your options if you have a history with breast cancer, cervical cancer, etc.

  5. I have had breast cancer twice now once at 35 and again at 48 two different types not a spreading of cancer. I have had genetic testing results were negative. Go figure!

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