"It's not a question of will I get breast cancer, but when…"
Unfortunately, I hear remarks like this from my patients quite often. And I spend a great deal of time explaining to them that if they have a few family members with breast cancer, it doesn't mean that the die is cast and they will automatically develop the disease. It's true at this point in time that family history is probably considered the most important factor when assessing breast-cancer risk. However, a number of other factors—including at what age the family member was diagnosed and how close the relation is—make a significant difference in determining a person's actual risk.
For example, the relative risk for women with a mother or sister (first-degree relative) who developed invasive breast cancer in the premenopausal setting or bilateral breast cancer is about 2.0 (about twice that of the general population). And to show you the difference, the relative risk for women with a grandmother (a second-degree relative) who developed breast cancer is lower, about 1.4 (40 percent greater than the general population).
Some people have family histories that reveal multiple cases of breast and ovarian cancer. These people with "hereditary breast-ovarian syndromes " represent about five to ten percent of breast-cancer cases. The inherited genes we hear the most about are BRCA-1 and BRCA-2. A mutation in BRCA-1 is associated with breast and ovarian cancer and a mutation in BRCA-2 is associated with male breast cancer.
It is quite likely that these genes have many functions, but most researchers agree that they act as tumor-suppressor genes. BRCA-1 and BRCA-2 genes are very large, and because of their size, there are lots of opportunities for mutations. Some mutations are in areas of the gene that don't code for anything very important, but other mutations are in critical areas. When a gene encodes a wrong message it ultimately produces a defective protein that can't do its job properly (its job is usually regulating how a cell behaves).
More than 100 mutations in BRCA-1 have been identified in breast cancer patients. In fact, some scientists have noted that there are certain areas where mutations result in concomitantly high rates of ovarian cancer as well (ovarian cluster regions). Scientists have further noticed that there are some mutations in BRCA-1 and BRCA-2 that seem to be common in women with breast cancer who are part of certain ethnic groups. We call these the "Jewish mutations" and they are seen in up to one percent of Ashkenazi Jewish women. Since these genes are so large and there seems to be a prevalence of specific mutations in Ashkenazi Jewish women, these women are frequently tested for these three specific mutations.
Getting Tested
Many people decide that they want to know if they carry a breast-cancer gene. An equal, if not greater, number of people decide that they don't want to know. The reasons for testing for the gene can range from wanting to find out why they developed breast cancer, to helping make a decision regarding prophylactic (preventive) surgery, or even to helping in assess risks for unaffected family members. The most common breast cancer genes that are tested for mutations at the present time are BRCA-1 and BRCA-2.
Health
It's always a good idea to know the limitations of a genetic test, and the best person to help with this is usually a genetics counselor. Hence, such a person is usually your first contact after you have indicated to your doctor that you wish to consider testing. After a woman meets with a genetics counselor, she will decide whether she thinks that a given result will help her. Blood is then drawn and sent to a laboratory for testing; it can take several weeks for a result to be returned. Usually, there will be a follow-up meeting with the genetics counselor to discuss results.
It is important to remember that genetic testing is in its infancy and we still have a lot to learn. If you are looking for concrete predictions, then genetic testing won't help you. However, if you think a positive or negative result will influence patterns of behavior, then it is probably worthwhile. There is no ideal time to be tested. Bear in mind that a person must be psychologically strong enough to handle a potentially positive result.
In my own experience, I've found that younger, unaffected patients are not emotionally equipped to handle this type of information. In addition, there are other potential issues for young, healthy people, like employment and insurance.
While it appears that safeguards for privacy are being put in place, my personal opinion is that it's too early to be confident that this information will never become public. Therefore, I would pay special attention to confidentiality issues and make sure that no routine office notes or mails make any reference to either a positive or negative test result.
Looking at the situations of two of my patients who elected genetic testing clearly demonstrates just how differently people use the information. One of these patients was 50 years old when she was diagnosed with a small, Stage-1 breast cancer. She had many relatives who had been diagnosed with breast cancer and certainly was considered high risk for an inherited syndrome. She immediately opted for a mastectomy (even though a lumpectomy would have been fine) and for chemotherapy (though she was considered a borderline candidate for treatment). She then underwent a prophylactic mastectomy, hysterectomy, and ovarian removal. She decided to have the last surgery even though genetic testing did not reveal any mutation.
My second patient was 23 years old when she was diagnosed with an early stage breast cancer. Her mother had died at age 37 from breast cancer, one of her mother's sisters developed breast cancer in her 40s (though currently healthy), and another aunt had undergone prophylactic mastectomies years earlier. Certainly, it seemed as though this patient was at high risk for an inherited syndrome. In fact, genetic testing confirmed that she did indeed have a mutation in BRCA-1 (a typical Jewish mutation, although she is non-Jewish). After initial treatment for her breast cancer, she has opted for observation alone and her multitude of cousins have declined testing.
It's important that you realize that each of these patients was right in the personal decision she made.
Unresolved Issues
There are many questions still to be answered regarding the connection between genes and breast cancer. For example: How many more mutations will be discovered? How does each aberration affect the lifetime risk of developing breast cancer? Are there other co-factors which contribute to the development of breast cancer (the so-called two-hit hypothesis)? Do patients who have inherited breast cancer have a different prognosis or respond differently to treatment? When the answers to these questions are discovered over the course of time, the importance of genetic testing will increase, and test results will provide much more directive information.
