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More Than Mammograms: MRI for High-Risk Women

Physicians and women have long awaited a better early detection tool for breast cancer than mammograms. And a recent study suggests that a new option, magnetic resonance imaging (MRI), can be added to the screening arsenal, though it's only recommended to women at high genetic risk for breast cancer.

Breast cancer screening is a top concern for women who have an inherited abnormality in one of two genes, known as the BRCA1 and BRCA2 genes. Yet few studies have examined what screening approach is best for these high-risk women. BRCA1 and BRCA2 mutation carriers are identified though blood tests that are given to certain women with a strong family history of breast cancer. Women of Ashkenazi Jewish descent are at particular risk: The mutations occur in about 2.5 percent of these women, compared to 1 percent of the general population.

A study published in the September 15th issue of the Journal of the American Medical Association looked at the usefulness of MRI, mammograms, ultrasound and clinical breast exams, which are breast exams performed by a healthcare professional, in screening healthy women with the BRCA1 and BRCA2 gene mutations for breast cancer. The researchers found that MRI, in which magnets and radiowaves create an image of a body part, was a helpful addition to the surveillance programs for these women.

Other risk factors for breast cancer include age, family history, use of hormone replacement therapy, radiation exposure, early onset of the menstrual period and late menopause. However, the JAMA study only examined women with one of the BRCA mutations. Breast cancers related to BRCA1 or 2 mutations make up about 5 percent of all breast cancers.

Below, study author Sandra Messner, MD, the medical coordinator of clinical breast services in preventive oncology at the Toronto Sunnybrook Regional Cancer Center, discusses the best screening options for these high-risk women to help make sure any breast cancer they develop is detected as early as possible.

What are the BRCA mutations?
There are two large genes that have been identified in all women called BRCA1 and BRCA2. They function, we think, as tumor-suppressor genes, so they keep cancers from developing. If they are abnormal or what we call mutated, then your risk of cancer is increased, and the risk of breast cancer and ovarian cancer particularly is affected. If a woman carries an abnormality in one of those two genes, she is thought to have up to an 85 percent lifetime risk of breast cancer. The average woman's lifetime risk of developing breast cancer is about 11 percent. The mutations also increase the risk of ovarian cancer, more so with BRCA1 than with BRCA2. The BRCA2 mutations may also increase risk of other cancers, such as melanoma and pancreatic cancer.

It is possible to carry mutations in both genes, but it is very rare. There is no conclusive data on risk in this situation, but most experts suggest that the risk is not any higher with both genes than only one.

What prevention strategies have been recommended to women with these mutations?
There hasn't really been any kind of standard approach, but women who carry mutations in these genes have several options. The most drastic is to have their breast removed with a preventive mastectomy. This reduces the risk of developing breast cancer by about 90 to 95 percent. It's a pretty drastic thing, however.

We also talk to these women about the potential role of tamoxifen, which works by blocking estrogen receptors in women with hormone-positive breast cancer, to reduce their risk of breast cancer. There have been some papers that suggest it's also beneficial in mutation carriers. But there have been a lot of questions about whether it's as beneficial in BRCA1 carriers as it is in BRCA2 carriers, because tamoxifen works by blocking estrogen receptors, and three-quarters of the cancers that are diagnosed in BRCA1 carriers are estrogen-receptor negative. With BRCA2 mutations, about 75 percent of cancers are estrogen-receptor positive.

However, people don't like to take drugs when they are healthy. One of the side effects with tamoxifen can be an increased risk of uterine cancer. The uterine cancer risk is less than 1 percent. But if you've already got a fear of cancer because you're at such high risk, that's a scary thing.

What kind of screening is recommended to women with BRCA1 and 2?
The current screening recommendation for mutation carriers is annual mammography starting somewhere between 25 and 35 and clinical examination of the breasts every six to 12 months. Breast self-examination has been recommended by some people, although that the effectiveness of this screening tool is controversial. The only difference between these recommendations and those for the average woman is that you might do the mammograms more often; yearly instead of every two years and you certainly would start at a younger age.

Why did you decide to conduct your study?
There is a question as to whether mammography works as well in women with the BRCA mutations as it does in the general population because the kinds of cancers that they get, especially with BRCA1, seem to be somewhat different. They don't, for some reason, show up on mammography as well as some of the other kinds of breast cancers that other women get, possibly because they are less likely to form a mass initially. Because MRI was an up-and-coming technology and seemed to be useful in detecting other medical conditions, it was being considered for breast cancer. So, along with ultrasound, which was another technology that people were suggesting we could add to mammography to give us more information, we thought we'd see which of the techniques was best or whether a combination of the techniques was best.

What did your study find?
When our study was published, there were 22 breast cancers that had been identified in more than 200 women. What was interesting was that a lot of these cancers were found only on MRI. Some were found only on mammograms, and ultrasound generally didn't, overall, seem to contribute very much. The MRI seemed to pick up the most cancers, and it seemed to pick them up at a relatively early stage.

Should a woman with BRCA1 or 2 be screened with MRI?
At this point, we're recommending that mutation carriers have MRI yearly and mammogram yearly starting between ages 25 and 30. Mammograms need to be done as well because some types of early breast cancer, specifically ductal carcinoma in situ, that show up on the mammogram as little specks of calcium, what we call microcalcifications, don't show up on MRI. We're not suggesting that women have the addition of ultrasound, because we think adding ultrasound doesn't really add much more. We also recommend a clinical breast examination twice a year.

Why isn't MRI recommended to the general public?
There are a lot of things that show up on MRI that aren't cancer, such as cysts and nodules, so you have to sort that out, hopefully, without having to do surgery to prove it. False-positive results are still a concern in women with the BRCA mutations, but the higher the risk of cancer, the more one is willing to tolerate the downside of false-positives.

But given the high number of false-positive results and knowing the technical problems with MRI, I don't think it will ever become a standard screening tool for the general population. It's expensive and time-consuming. It often takes almost an hour to do a screen. It involves an injection for the imaging. There is also a big issue regarding claustrophobia because the space inside the magnet is smaller in a breast MRI machine than it is in a regular MRI machine.

Do you recommend MRI to all high-risk women?
The results of our study are applicable only to mutation carriers. This does not imply that MRI is beneficial for all high-risk women because there are many other reasons for women to be at high risk, and we don't yet have evidence to say that all high-risk women should get MRI screening.

What research questions are still unanswered?
There's a whole question of: Do you alternate between MRIs and mammograms? Do you do something every six months? Also the question has been raised: Would it be better to do only MRI in women when they're very young since their breasts are very dense, making mammograms hard to read? These are all questions that we're playing with to figure out what would be ideal. The next step in our study is to see if we've had an impact on survival, because, obviously, that's the endpoint that we really want to reach.

What is your overall advice to a woman with one of the BRCA mutations?
Given the fact that the field is constantly changing and there are new recommendations and new studies coming out all the time, I think that it's important to hook yourself up with a high-risk program, if you possibly can. There are issues not just around breast cancer, there are issues around ovarian cancer. With BRCA2, there is increased risk of melanoma and pancreatic cancer. There are also psychological issues. This is a very scary thing for women, and most high-risk programs offer psychological counseling. So my advice is to try to get your screening through a high-risk program.

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