© 2005-2012 American Society of Clinical Oncology (ASCO). All rights reserved worldwide.
At age 40, it is recommended that women continue monthly self-breast exams, have a clinical breast exam each year, and begin having an annual x-ray of the breast, called a mammogram. These three methods of screening are intended to work together to help detect breast cancer as early as possible, when treatment is most likely to be successful.
Doctors now know that the risk of breast cancer increases with a family history of the disease, including abnormalities in the BRCA genes. Mutations in the BRCA1 and BRCA2âabbreviations for "Breast Cancer Gene 1" and "Breast Cancer Gene 2"âare associated with about 5%-10% of all breast cancers.
For women with a high risk of breast cancer, experts recommend that they have their first mammogram at age 30, or five years before the earliest onset of the disease in their family.
However, while mammography is the best tool for detecting breast cancer in women at an average risk for the disease, there is some uncertainty over the best type of imaging technique that should be used to screen women at high risk. Some research has suggested the use of magnetic resonance imaging (MRI), in addition to mammography, to screen women at high-risk for breast cancer. An MRI uses a magnetic field to produce the image of an internal organ on a computer.
To determine whether MRI should be added as a screening method in high-risk populations, researchers led by Christiane Kuhl, MD, of the University of Bonn in Germany, studied 462 women who were found to be carriers of BRCA1 or BRCA2 or who, based on their personal history or strong family history, were suspected to be carriers of BRCA1 or BRCA2.
In this study, a strong family history was defined as any of the following: a relative with a breast cancer diagnosis at age 35 or younger; a relative with ovarian cancer diagnosed at age 40 or younger; both breast and ovarian cancer in a relative; or at least two relatives with breast and/or ovarian cancer, one of whom was diagnosed at age 50 or younger.
All women in the study were screened with a clinical breast examination, mammography, high-resolution ultrasound of the breastâa technique that uses sound waves to detect abnormalities in body tissuesâand an MRI. For the first five years of the study, researchers found 51 breast cancers in 45 patients.
MRI offered the highest sensitivity for diagnosing breast cancer at 96.1%, compared with 42.8% for mammography, 47% for ultrasound, and 25% during a clinical breast exam. MRI was also associated with the lowest rate of unnecessary biopsies, a procedure that removes a small piece of tissue for examination under the microscope to help detect cancer.
Because of these findings, the researchers concluded that MRI of the breast should replace mammography to screen women with a strong family history of the disease or women who have known BRCA mutations for two reasons:
1) These women tend to start screening earlier when their breasts are more dense and the sensitivity of mammography is therefore low.
2) Women with BRCA mutations are more sensitive to the effects of radiation (that they are exposed to during a mammography), which can cause genetic mutations that may lead to cancer.
A team of Dutch researchers reported similar findings. As part of the Dutch MRI Screening Study (MRISC), researchers from several institutes in the Netherlands evaluated the benefit of twice-yearly clinical breast examinations, yearly mammography, and yearly MRI in 1,905 women at high risk of breast cancer due to a mutation in the BRCA 1 or BRCA 2 gene or a strong family history of the disease.
"We recommend the routine use of MRI in addition to mammography, especially in women with proven mutations in the BRCA1/2 genes, because these women generally develop rapidly growing tumors and show the lowest sensitivity to mammography because of their young age and dense breast tissue," said Jan G.M. Klijn, MD, PhD, Chairman of the Rotterdam Family Cancer Clinic and a lead investigator of the study.
During an average follow-up period of two years, 40 breast cancers were found. In the 1,905 women, many (46%) of the tumors were smallâone centimeter or less in sizeâand 77% of patients had lymph nodes that were free of cancer cells, which means that the cancer had not spread beyond the breast.
While clinical breast examination detected 16% of the tumors and mammography detected 36%, MRI was significantly more effective at detecting 71% of the breast cancers. For women with invasive breast cancer, MRI detected 83% of the tumors compared with mammography, which detected only 26%.
However, while MRI was found to be more effective at detecting tumors of the breast than both mammography and clinical breast examination, it was also found to be slightly less specific. Lower specificity means that it is more likely to produce false positive results. False positives can lead to unnecessary biopsies and anxiety for patients.
A third study evaluating the benefit of MRI for women at high risk for breast cancer found that MRI needs to be refined before its use can be recommended, even for women at high risk for the disease, due to a high rate of false positives.
"The psychological impact of a false-positive MRI is not trivial," said Mark E. Robson, MD, Assistant Attending Physician at Memorial Sloan-Kettering Cancer Center, in New York, NY, and lead investigator of the study.
In a trial of 53 women with BRCA mutations who participated in MRI screening, researchers found that MRI was 100% sensitive for detecting both ductal carcinoma in situâa precancerous breast conditionâas well as breast cancer. However, it was only 81% specific.
"The improved sensitivity of MRI screening is very encouraging," said Dr. Robson. "MRI can clearly detect breast abnormalities that are not seen by mammography. Unfortunately, we are finding that many of these abnormalities are not cancers."
Until the specificity of an MRI can be improved, Dr. Robson recommends that women who are considering an MRI be aware of the significant risk of false-positive results.