BRCA Testing

You might be a candidate for BRCA testing if your family has:

• Two or more members with breast and/or ovarian cancer. Note that the evidence of a mutation is just as strong if your mother has breast cancer and your sister has ovarian cancer as it would be if both had breast cancer. And because ovarian cancer is much rarer than breast cancer, two such cases are even more suggestive of an inherited mutation.
• A relative whose cancer was diagnosed at a young age (under 50). Multiple incidences of early-onset breast or ovarian cancer are the No. 1 tip-off that a BRCA1/2 mutation might be lurking in the family. About three-fourths of breast cancers are diagnosed after menopause, so a younger age of onset serves as a good red flag.
• An incidence of breast and ovarian cancer in the same woman, or two separate primary breast cancers in the same woman.

Your ethnic background may come into play with breast cancer risk as well, if you are of Ashkenazi Jewish descent. Women with such a background are about 10 times more likely to have a mutation than women in the general population. If you are of Ashkenazi Jewish descent, you may also consider testing if one family member has been diagnosed with breast cancer before the age of 45. Testing looks for three specific mutations that account for 90 percent of the positive BRCA1/2 gene changes in this population. If the test comes up negative in the face of a strong family history, a comprehensive BRCA full-sequence analysis may be ordered.

As you think about your family history and any associated risk, be sure to look at your father's side, as well as your mother's. If women on his side of the family have a mutation, you face as much risk of inheriting it as you do of inheriting a maternal-side defect.

If you are not sure but think there's a possibility that your family has a hereditary cancer pattern, talk to a genetic counselor. Genetic testing for cancer predisposition is an individual choice for adults. Some women prefer not to get tested, and some young women prefer to wait.

Did You Test Positive?

If you test positive for a BRCA mutation, there are options for minimizing your cancer risk, but none of them reduce your risk to zero:

• Stepped-up screening and prevention efforts. If you test positive, mammography is recommended starting at age 25 and repeated annually. You should do a breast self-exam once a month, at the same time of the month. If you're premenopausal, you may want to do it the week after menstruation. A clinical breast exam by a physician is also recommended every six months (instead of the usual once a year).
• Chemoprevention, or taking medications to reduce your risk. Tamoxifen, a treatment for breast cancer, can cut breast cancer risk 50 percent in high-risk patients. Raloxifene, a similarly designed drug that is approved for preventing osteoporosis is also under study as a cancer-preventing agent. Oral contraceptives containing estrogen and progestin can cut ovarian cancer risk up to 60 percent.
• Prophylactic surgery to remove the breasts (mastectomy) and/or ovaries (oophorectomy). This is the most radical option, but some women choose it because of the high lifetime risk of cancer that accompanies BRCA1/2 mutations.
• Oophorectomy is increasingly being recommended for women who test positive for BRCA mutations and are either finished with childbearing or are certain that they do not want children. Removal of the ovaries not only reduces ovarian cancer risk 90 to 95 percent, it also reduces breast cancer risk 50 percent. That's because the ovaries produce estrogen, which stimulates breast growth and is linked to cancer risk. The bad news is that removing the ovaries also removes your body's source of estrogen. Therefore, estrogen levels diminish rapidly and trigger menopausal symptoms, such as hot flashes, vaginal dryness and bone loss, among other short-term physical and emotional changes and long-term health risks associated with menopause. For some women, "surgical menopause," when one or more ovaries is removed, can trigger more sudden and severe menopausal symptoms than when menopause occurs spontaneously at the end of a woman's childbearing years-a transition that typically takes about five years in a woman's late 40s.

Postmenopausal hormone therapy (often referred to as hormone replacement therapy or HRT) can be prescribed prior to or just after surgery to mitigate menopausal symptoms. However, women, health care professionals, and the Federal government are scrutinizing the use of postmenopausal hormone therapy more closely than ever before and its safety for both long-term and short-term use is in question.

In January 2003, the U.S. Food and Drug Administration (FDA) announced that it would require a new, highlighted and boxed warning on all estrogen products for use by postmenopausal women. The so-called "black box" is the strongest step the FDA can take to warn consumers of potential risks from a medication. The warning highlights the increased risk for heart disease, heart attacks, stroke and breast cancer from supplemental estrogen-risks illuminated by part of the Women's Health Initiative study, which was abruptly halted in July 2002 when the risks were identified.

The "black-box" warning also advises health care professionals to prescribe estrogen products at the lowest dose and for the shortest possible length of time. Women taking estrogen products are cautioned to have yearly breast exams, perform monthly breast self-exams and receive periodic mammograms.

Because every woman's risk profile is different, women who are thinking about taking postmenopausal hormone therapy or are currently taking it for whatever reason, need to review their options and treatment plans with their health care professional in light of the FDA's recent warning.

New, lower-dose versions of the hormone therapies used to treat symptoms of menopause are currently being developed. The FDA recently approved a low-dose version of the combination estrogen-progestin treatment sold as Prempro, which is expected to be available in the summer of 2003.

Families with hereditary cancers may choose to participate in research studies and familial cancer registries. This option helps researchers identify new cancer-associated genes and ultimately may aid the design of better cancer therapies. Registries and research are typically housed at the nation's leading cancer centers, so participation can also provide better access to top-quality, cutting-edge care. Participants give informed consent and their privacy is protected.