Genetic Testing: Families With Breast Cancer

Ms. G. is a 40-year-old woman with two small children. Like most women, she is concerned about her chances of developing breast cancer. She asks her doctor about her risks. Although breast cancer is a worry for most women, Ms. G. is especially worried because of a family history of breast cancer. Her mother and sister had breast cancers that were diagnosed at young ages.

A woman with a family history of breast cancer has a lot of concerns. Among other things, she is thinking of her job, children, and husband, as well as how her medical insurance and health team will be able to serve her needs in the future should she be diagnosed with breast cancer.

Overall, inherited breast cancer disorders account for a small minority of breast cancers. Genes are the "messages" in each cell of the body that determine the ultimate design of our bodies. Genes can be damaged by the environment. Additionally, people can be born with defects in the genes that remove the body's defenses against cancers. Only in about 10% of all breast cancer cases is there actually an inherited genetic defect that can be detected by testing. In fact, most cases of breast cancer occur in women who do not have a family history of breast cancer. A complex interplay between environmental and genetic factors affects the development of breast cancer, and all the key factors have not yet been identified.

The whole issue of genetic testing for breast cancer is complicated. Recent research indicates that the information women seek most often when they request genetic testing does not match what they can realistically determine from this testing. Nevertheless, it is worthwhile to consider the role of this testing and what it involves.

Certain characteristics make a woman at higher risk for genetic breast cancer disorders. These factors include:

1. family members with breast cancer, especially at a young age;
2. breast cancer in a male family member;
3. both breast and ovarian cancer in the family;
4. bilateral breast cancer in a single family member;
5. breast cancer diagnosed at very young ages; and
6. being of Ashkenazi Jewish descent.

Ms. G. and her doctor determine that she falls within the group with higher risk factors because her sister and mother both had breast cancer at young ages.

First, an expert reviews the family medical history to evaluate what sort of pattern of genetic breast cancer may be occurring. Next, the family member's tumor sample, if available, undergoes testing. It is impossible to run tests to analyze every single gene in a woman. Therefore, the nature of the specific disorder is narrowed by testing of the specific tumor from an affected family member. The tests are designed to determine if any of the known inherited genetic breast cancer genes is present. If the defect is found on the tissue sample of the woman's relative, the lab will then know exactly which defect should be tested in the blood sample of the woman herself. In this way, a woman will be able to be counseled about her own risk. Counseling, education, and emotional support are provided both before and after any testing, no matter what the result.

Prior to undergoing testing, it is essential that women consider the benefits and risks in light of the possible results. For example, if her test is positive (meaning she is affected by a genetic disorder) there are measures that can reduce her breast cancer risk. One of these is having breast tissue surgically removed, knows as prophylactic mastectomies. This is an unpleasant prospect for many women. Removal of the ovaries also appears to be helpful in reducing risk.

Tamoxifen (Nolvadex) and raloxifene (Evista) are two members of the class of drugs known as selective estrogen receptor modulators (SERMs) that have been shown in clinical trials to be effective in preventing breast cancer in women at high risk for the disease, but there are fewer data available on their effects in women who are BRCA mutation carriers. There have been no studies that show that tamoxifen actually prolongs survival in women at high risk for breast cancer, and rare but serious adverse events (uterine cancer, blood clots) have been reported. Raloxifene has been tested and shown to be effective in preventing breast cancer in postmenopausal women but its effectiveness is unknown in younger women. There are no medications specifically approved for use in reducing the risk in women with genetic mutations (BRCA genes) that are known to increase susceptibility to breast cancer.

While Ms. G. is considering these surgery options, she must also decide a variety of issues such as:

• whom she would tell,
• whether her own children should be tested, and
• how her health insurance and/or job will be affected.

The Genetic Information Non Discrimination Control Act of 2008 and the Affordable Care Act of 2010 have lessened concerns about insurers taking away insurance based on genetic testing. If she does not desire to inform anyone about a positive test and would not consider having surgery, then perhaps she may not want to be tested in the first place. On the other hand, what if the test results for Ms. G. are negative? This may be a relief. However, there is also the frustrating fact that even if a woman has a negative genetic test, she is still at higher risk for breast cancer than the general population due to the risk factor of having multiple family members with breast cancer. Another possibility with genetic testing is that a non-typical alteration in a breast cancer-related gene is detected, the significance of which is unclear.

Although most women who are surveyed think breast cancer is the leading cause of death in women, heart disease is actually the leading cause of death in women. Heart disease kills one out of two women, far in excess of the number of deaths caused by breast cancer. Breast cancer occurs in nearly 240,000 women each year, but only about 40,000 die of it each year. It is important to keep the perspective that most women who have only one family member with breast cancer should actually be more concerned with discussing heart disease prevention with their physicians than breast cancer prevention.