Understanding Genetics and Breast Cancer – Early Detection & Prevention

By Debra Wood, RN

A nagging fear of being next can haunt a woman when breast cancer runs in a family. But a little knowledge about one’s genetic makeup can give women power over the unknown.

Diana Ravicchio, of Los Alamitos, California, rests easier these days, despite knowing she carries one of the genes associated with an increased risk of breast and ovarian cancer, because she has taken action to decrease her risks. Likewise, a negative genetic test result for a specific mutation previously identified in a family member overjoyed and relieved Joanne Lewis of Melbourne, Florida.

Cancer’s Genetic Connection

Everyone inherits altered forms of some genes, but certain alterations can result in an increased risk for diseases such as breast cancer. A genetic alteration in a cancer-related gene can cause malignant mayhem as the cells receive instructions to continue dividing or do not receive a message to stop growing.

“Genetic alterations are part of all cancers,” says Susan M. Domchek, MD, assistant professor of medicine, University of Pennsylvania. “It depends whether the change happens in the cell or was an inherited factor passed down.”

Inherited mutations that cause increased risk for cancer account for less than 10% of all cancers. Two genes are responsible for the majority of hereditay breast and ovarian cancer in families. These genes are known as BRCA1 (breast cancer 1) and BRCA2 (breast cancer 2). Women who inherit a mutation in one of these two genes have up to an 87% lifetime risk of developing breast cancer as well as up to a 65% risk of developing a second primary cancer. These women also have a significant risk of developing ovarian cancer (up to 44% in their lifetime).

“BRCA1 and BRCA2, in their normal state, function to suppress changes that can lead to cancer,” says Julie Gralow, MD, associate professor of medical oncology, University of Washington School of Medicine. “We all have these genes. When they are normal, they help with preventing cancer.”

Features associated with a higher risk of the mutation include: 1) early age at breast cancer diagnosis (under 50); 2) multiple family members with breast cancer on same side of the family (either maternal or paternal); 3) one case of ovarian cancer in family with breast cancer history; 4) male breast cancer; and 5) ethnic background (BRCA1 and BRCA2 mutations are more prevalent in individuals of Ashkenazi Jewish decent). It is important to note that even in families with a known mutation, not every woman in the family inherits the mutated gene. And having a mutation does not equate with a cancer diagnosis now or down the road, but it significantly increases the risk of certain cancers.
Mara Galaty, of Portland, Oregon, and a patient of Dr. Gralow’s, discovered she was BRCA2 positive after being diagnosed with breast cancer at age 32. Her mother had the disease and her grandmother had ovarian cancer. Her sister also tested positive but her aunt, negative.

Based on these results, her sister has increased her medical management to reflect her increased breast and ovarian cancer risks and her aunt has been able to reduce her screening for these cancers to the level of women in the general population.

“You are born with one copy of the gene that doesn’t work,” Dr. Domchek says. “At some point, genetic changes occur and then both copies have alterations. When you start with one already damaged, it’s easier to have the second event happen.”

Researchers have tied other gene mutations to breast cancer, but BRCA1 and BRCA2 are the ones identifiable with a genetic blood test at the current time.

“The main reason to be tested is we feel we can change the odds of people getting cancer,” Dr. Domchek says. “We can change the course of this disease and decrease the risk of developing cancer or find it earlier with enhanced screening.”

Genetic testing

Almost all the women on Ravicchio’s father’s side died of breast cancer. Her paternal grandmother died at 31. Ravicchio, the mother of twins, received some false assurances from medical professionals that she was not at risk. But she researched the topic and persisted. Finally, her dad was tested and learned he had the mutation. Unfortunately, the myth that the father’s family history of breast or ovarian cancer has nothing to do with a woman’s own risk is still popular in the medical community (see sidebar for additional myths).

While genetic testing presents very personal information, it also can deliver results that affect family members. Before testing, each person should consider what relatives you would want to share the results with.

“Sometimes when an individual receives bad news about her BRCA1/2 genetic status, it can be very devastating,” says Karen Charles, a genetic counselor at M. D. Anderson Cancer Center, Orlando. “Feelings of guilt and shame can prevent sharing test results with other family members.”

Lewis’ sister, who has breast cancer, tested positive for a mutation. “I was relieved with my negative results,” Lewis says. “But at the same time felt bad for my sister and questioned why.”

The identification of a BRCA1 or BRCA2 mutation in an individual has implications for future generations. If a man or woman tests positive for a BRCA1 or BRCA2 mutation, they may pass the mutation on to approximately 50% of their children. This is true even if the parent never develops cancer themselves.

To help deal with these issues, testing begins and ends with a genetic counselor. Before meeting, the counselor may ask you to research your family tree.

“We start with the family history, then we talk about the genetics of cancer, the testing procedure, and its risks, benefits, and limitations,” Charles says. “Going hand in hand with the educational aspects is providing psychosocial support. Cancer can sometimes trigger memories and feelings of guilt or anxiety.”

Genetic counseling, of which genetic testing is just one part, encompasses professional counseling and medical investigation. Genetic counseling sessions can last a couple of hours, and patients may go home to digest the information before proceeding. Results take about a month to arrive.

For Ravicchio, a positive result—meaning she was at increased risk for breast and ovarian cancer—convinced the young woman to undergo surgery to remove her ovaries and a double mastectomy with immediate reconstruction. All her tissue was cancer-free.

“It didn’t affect my femininity or sexuality at all. I feel exactly the same,” Ravicchio says.

Physicians advise women to consider testing only if the results will alter their medical management. Nonsurgical options for women testing positive include more extensive cancer screenings, reducing modifiable risk factors by exercising regularly and decreasing alcohol consumption, chemoprevention (which involves taking Nolvadex® [tamoxifen] or another medication to lower the risk), or participating in a clinical trial. However, little data exist to confirm effectiveness of these options.

Genetic testing may not produce definitive answers. If the test shows an alteration in one of the genes that has not been associated with cancer, the test can be interpreted as uninformative. This alteration could represent a harmless variation common in that family or could be related to increased cancer risks. Likewise, a negative result is also considered uninformative if the presence of a mutation has not been confirmed in a family member. A negative result drops a woman’s breast and ovarian cancer risks to that of women in the general population. And it is important to remember that having a mutation does not guarantee a diagnosis of cancer.

“If you’ve already tested other family members and you know where to look, and it comes back negative, that’s helpful,” Dr. Gralow says. “If you can’t find it in the family, it may be a mutation we don’t know how to test for yet. It doesn’t mean there [are no mutations] in the family.”

Typically, a person diagnosed with breast cancer at an early age or a family member with ovarian cancer will test before other family members to determine if a mutation is present. The cancer patient can also determine her risk for ovarian cancer or a recurrence.

“Testing gives you useful information,” says Galaty, who was tested after her diagnosis. “It causes you to live your life in a more responsible way, to think about things.”

The results prompted Galaty to have a double mastectomy and enter an ovarian cancer early detection clinical trial. She and her husband agreed that adoption would be preferable to giving birth to avoid the increazse in estrogen that occurs with pregnancy.

Most major cancer centers offer genetic testing. And the National Cancer Institute offers lists of genetic counselors
(www.cancer.gov/search/genetics_services/). A free genetic testing video is available from Myriad Genetic Laboratories by calling 800-469-7423 or visiting www.bracanalysis.com.

Genetic testing can cost up to $3,000 for the first family member tested. Coverage varies by insurance policy. Once someone in a family tests positive and the location of the mutation is known, less expensive tests can check that specific spot for a mutation. Many insurance companies cover genetic counseling if a reasonable risk exists based on family history.

Some women worry about insurers learning the results or job discrimination. The Health Insurance Portability and Accountability Act protects people with group health insurance provided by an employer. The insurer cannot consider genetic information a pre-existing condition and use it to limit or deny coverage. Also, some states have passed genetic antidiscrimination laws. And some women opt to purchase life insurance before testing. Discuss these issues with the genetic counselor. Anonymous testing or participation in a clinical trial can keep the information out of your medical record.

Testing is not for everyone at increased risk. Children should not be tested for the mutations, because there is no evidence of BRCA1 or BRCA2 causing childhood cancers. Some women have trouble coping with “bad news.” Others just prefer not knowing or want to wait until better medical options exist for dealing with a positive test result.

“I have no regrets about testing—none,” Ravicchio says. “I don’t think about cancer anymore. I can sleep and not worry about it. My chances of getting breast cancer have been reduced by 99%, and those are pretty good odds.”


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