How DNA influences breast cancer risk

01:40, May 16 2013

By opting for surgery to remove her breasts while they were still healthy, Hollywood actress Angelina Jolie joined a growing number of women who have used genetic testing to take control of their health.

Here are answers to some common questions about how DNA influences breast cancer risk and what women can do about it.

Question: What genes are involved in breast cancer?

Answer: The two primary ones are known as BRCA1 and BRCA2. Hundreds of variants of these genes have been found that make a woman - or a man - more likely to develop breast cancer. The mutations can increase one's lifetime risk of breast cancer from about 50 per cent to more than 85 per cent, said Rebecca Nagy, president of the United States National Society of Genetic Counselors.

In her essay in The New York Times, Jolie said her doctors believed the mutation found in her BRCA1 gene raised her chance of developing the disease to 87 per cent.

Scientists know of variants in other genes that also play a role in breast cancer, but these occur more rarely than the BRCA mutations, said Nagy, who works at Ohio State University's James Cancer Hospital in Columbus.


Q: How many people have these mutations?

A: Everyone has the BRCA1 and BRCA2 genes, but only about 1 in 600 women have variants known to increase the risk of breast cancer, said Ellen Matloff, director of cancer genetic counselling at the Yale Cancer Center in New Haven, Connecticut.

The variants are more common in certain groups of people, including Jews from Europe, and are also linked to ovarian cancer in women. BRCA2 mutations, additionally, are associated with an increased risk of pancreatic cancer, Matloff said. Other cancers have also been linked to mutations in the two genes.

Q: Should I get tested to see if I have these mutations?

A: Not necessarily. At the Yale Cancer Center, genetic counsellors only recommend testing for people who have a strong family history of a type of cancer that is known to be linked to these genes: breast cancer before the age of 45, several family members with the disease on the same side of the family, breast cancer and ovarian or pancreatic cancer on the same side of the family, a family history of male breast cancer, or Jewish ancestry combined with even one case of breast or ovarian cancer in the family.

Matloff emphasised that most cases of breast and ovarian cancer are not related to these mutations.

Q: How does the test work?

A: Generally, a woman who is concerned about her cancer risk begins by consulting her GP and a genetic counsellor, who can examine her personal and family history to determine what tests might be useful. A genetic counsellor can also discuss the pros and cons of testing, including implications for other family members, Matloff said.

The test involves collecting a sample of blood or saliva and sending it to Myriad Genetics, a company that performs the analysis and can deliver a report on which variants you have and how much these variants increase your risk of various types of cancer.

However, Matloff warned that sometimes the test results are misinterpreted, with variants that are not known to cause cancer confused with variants that do.

"We've found that a lot of women who've had this surgery had their test results read incorrectly," she said.

Q: If the test says I have a high risk of breast cancer, should I have my breasts removed?

A: That is a very personal decision that patients should make in consultation with their families and doctors. Cosmetic factors and the availability other options - including heightened surveillance for early signs of disease or taking a drug such as tamoxifen, Matloff said - can come into play as a woman makes her decision.

Nagy said studies have estimated that at least 35 per cent of women who have a dangerous BRCA mutation decide to get the surgery when they are still healthy. Doing so can reduce their lifetime risk of breast cancer to less than 5 per cent.

Q: Why doesn't it reduce the risk to 0 per cent?

A: Even after a double mastectomy, some breast cells remain - and there is always a chance that cancer could develop in this tissue, Matloff said. However, a risk of less than 5 per cent is much lower than the 12 per cent to 13 per cent risk faced by a typical woman, she added.

Q: What is involved in a mastectomy?

A: All mastectomies involve removal of most of the breast tissue, but patients have options when deciding whether or how to have their breasts reconstructed, said Dr Maureen Chung, a surgeon and medical director of the Margie Petersen Breast Center at St John's Health Center in Santa Monica, California.

"The trend is to leave more and more behind," she said, noting that increasingly women are choosing to keep their skin, areolas and nipples intact for a better cosmetic outcome.

Breast reconstruction can take place when the breast tissue is removed or later, depending on the type of reconstruction a woman chooses, Chung said.

In Jolie's case, tissue expanders were put in place for a couple of months to create a pocket to accommodate breast implants.

Q: Are there any risks involved?

A: There is always a risk involved in any surgery, but generally speaking the procedure is very safe, Matloff said. You can live a healthy life without your breasts - and reconstructed breasts can look very good.

Q: What about having your ovaries and fallopian tubes removed?

A: This surgery is also routine but one consequence is that women who have it no longer have the estrogen produced by the ovaries; as a result, they go into a kind of early menopause.

However, a lot of women who have their ovaries removed are good candidates for hormone replacement therapy, Matloff said.

According to Nagy, about 70 per cent of women with dangerous BRCA mutations choose to have their ovaries removed eventually. The numbers are higher than for mastectomies because it is very difficult to screen for ovarian cancer.

- Los Angeles Times