Breast Cancer Prevention: High-Risk Women Face Difficult Decisions

Up to now, most women who have relatives with breast cancer have been able to breathe a sigh of relief after undergoing testing for the BRCA1 and BRCA2 genes, the two genes that have been strongly linked to breast cancer and ovarian cancer risk. Most women who are tested, after all, do not carry these genes. But a new study tells us that high-risk women with negative BRCA tests should not feel so reassured. Women who do not have these genes still have an alarmingly high chance of getting breast cancer if they have cancer in multiple family members.

How high is your risk, if this is your story, and should you opt to participate in some of the more extreme strategies to detect or prevent breast cancer? These measures include early screening with breast MRI, surgery, or hormone therapy.

The study about BRCA-negative women was conducted in Toronto and presented on November 17, 2008, at a meeting of the American Association for Cancer Research. To be in the study, a woman had to have at least two first- or second-degree relatives who developed breast cancer before the age of 50, or three first- or second-degree relatives who got breast cancer at any age. From this group, 1,500 women from 365 families tested negative for BRCA1 and BRCA2 mutations. After five years, the number of breast cancer cases that had been newly identified among the women who tested negative for BRCA genes was 4.3 times higher than what is seen in average women.

Even though having a negative BRCA test might not mean you are protected from getting breast cancer, a negative test does reassure women that their risk for ovarian cancer is not increased. Both of the BRCA genes are associated with ovarian cancer, as well as breast cancer.

But for women from a breast cancer-prone family, how much protection does a negative test give you from breast cancer? Not very much. Women who carry a BRCA1 or BRCA2 mutation in their genes have a lifetime risk for breast cancer that is between 65% and 85%―in other words, it is more likely than not that a woman will eventually get cancer if she has one of these genes. Based on the results from this latest study, women who have a very strong family history of breast cancer have a lifetime risk that is at least 50%, even without having a BRCA gene.

Women who know they are at high risk for breast cancer can, if they choose, take aggressive measures to prevent breast cancer or to find it in its earliest stage. These extra steps are taken by many women with BRCA genes. It is reasonable to think about these strategies if you are a woman who doesn’t have a BRCA gene, but who does have a concerning pattern of breast cancer in your family. These strategies include:

· Breast examinations by your doctor every 3 to 6 months
In between the times that your doctor examines you, a monthly self-exam is recommended. Breast examinations by your doctor should begin at age 25 for high-risk women.

· Breast MRI
The American Cancer Society (ACS) recommends that women with a high risk for breast cancer should get a yearly magnetic resonance imaging (MRI) scan of the breast, in addition to a yearly mammogram. According to the ACS, up to 1.4 million women in the United States should be getting annual breast MRI scans. The MRI scan is more sensitive than a mammogram, so it finds some cancers that a mammogram misses. The MRI scan also has a higher risk of giving a “false positive” result—a significantly higher number of biopsies must be done to follow up on findings in breast MRI tests, relative to mammograms. Because of the high false positive rate, it is not practical to use the MRI scan to screen women who are at average or low risk for cancer. For women with a strong family history that has affected relatives at a young age, MRI tests and mammograms can begin around age 25.

· Tamoxifen treatment after menopause
The drug tamoxifen (Nolvadex or Tamone) is a hormone that blocks the effect of estrogen. Five years of treatment with tamoxifen can reduce breast cancer risk by about 40% during the years it is used for treatment, and it probably has some benefit beyond that time. A decision about whether to use Tamoxifen is a challenging one for doctors and patients because the drug may cause worrisome and bothersome side effects. Possible side effects from tamoxifen include a more than doubled risk of uterine cancer, a tripled risk for a blood clot in the leg or lung, a 50% increase in stroke risk, hot flashes, night sweats, and vaginal discharge.

Another hormonal medicine, raloxifene (Evista), is able to lower breast cancer risk with about as much success as Tamoxifen, but it causes some of the same serious side effects. Raloxifene has not been formally approved for the prevention of breast cancer in a woman with no cancer history.

· Surgical removal of the breasts
If you have your breasts removed, you can reduce your breast cancer risk to nearly zero. Options range from a total mastectomy to a more cosmetically attractive surgery known as a skin-sparing mastectomy (although this can leave behind a small amount of breast tissue, so it does not lower your risk as fully).

Whether you choose for or against adopting one of these more extreme strategies to prevent breast cancer, you will make a decision that is difficult, courageous, and quite personal. Take time with these decisions, and talk with your family and your doctor as you consider them.

Do you have breast cancer in more than one family member, and have you considered having genetic testing? Would you consider taking one or more aggressive measures to prevent breast cancer?

Mary Pickett, M.D., is an Associate Professor of Medicine at Oregon Health & Science University where she is a primary care doctor for adults. Her field is Internal Medicine. She is also a Lecturer for Harvard Medical School and a Senior Medical Editor for Harvard Health Publications.

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