Commentary by Daniel Green MSIV and Boris Kobrinsky MD, Assistant Professor, NYU Division of Oncology
In 2008, an estimated 182,460 women in the United States will be diagnosed with invasive breast cancer, and 40,480 women will die of the disease as it remains the demographic’s second leading cause of cancer mortality.(1) Fortunately, breast cancer is one of the screenable cancers, and screening mammography has been shown to detect asymptomatic breast cancer at an early stage and reduce all-cause mortality when followed with appropriate treatment.(2,3) However, plain mammography has a sensitivity of about 85 percent, resulting in an estimated 21.8% of cases that are node positive at the time of diagnosis.(4)
The use of MRI in breast cancer screening is receiving increased attention, and the American Cancer Society has recently recommended it as an adjunct to plain mammography in the screening of high risk patients.(5) These patients include women with dense breast tissue, a personal history of breast cancer or lobular carcinoma in situ, prior mantle irradiation for Hodgkin’s lymphoma, and a strong family history of breast cancer.
Women with inherited BRCA1 and BRCA2 mutations have the greatest risk of breast cancer. Though only five to ten percent of women with breast cancer have one of the two mutations, those with a BRCA genotype have a lifetime risk of 65 to 80 percent of developing the disease.(5) This population tends to develop more aggressive breast cancers with significant risk of disease starting as early as age 30.
Several large, prospective, nonrandomized trials have been conducted to evaluate the use of MRI as an adjunct to plain mammography in screening high risk women for breast cancer. The largest of these studies, conducted in The Netherlands and published in 2004, evaluated both MRI and mammography in 1,909 high risk women.(6) The investigators found high sensitivity of MRI (80 percent) compared to that of mammography, whose sensitivity plummets to 33 percent in this high risk population. On the other hand, MRI had lower specificity than mammography (90 and 95 percent, respectively). Several other studies in North America and Europe have recapitulated these results.(7-11)
These studies were included in a recently published meta-analysis of 11 prospective studies on screening women at high risk of breast cancer with a combination of MRI and plain mammography. The investigators concluded that screening with mammography plus MRI may exclude breast cancer better then mammography alone in a population of women with a strong genetic predisposition to breast cancer.(12)
Enhancement of invasive breast carcinomas in contrast studies with gadolinium enables the increased sensitivity of MRI. However, many benign breast lesions enhance with gadolinium, resulting in a lower specificity. In women not characterized as high risk, the likelihood of false positives may lead to an unacceptable amount of recalls and biopsies. Because of the increased cancer rate in high risk women, the incidence of benign biopsy following MRI is similar to that of a population-based study using plain mammography.(13) In these patients, the benefit of high sensitivity MRI may outweigh the effects of lower specificity, though data on survival are not yet available.
A recent study from Stanford University evaluated the cost-effectiveness of supplementing screening mammography with MRI for carriers of BRCA mutations.(14) Health benefits were measured in terms of total health-related costs and quality-adjusted life years. The researchers found that screening MRI was more cost-effective in BRCA1-positive women compared to BRCA2-positive women because BRCA1 mutations confer a higher risk of breast cancer. However, they did not find that women with BRCA1 mutations aged 25-34 were at high enough risk to justify annual MRI screening. In addition, women with BRCA1 mutations over the age of 55 suffered from declining quality of life and competing risks for death, thus rejecting MRI as cost-effective for this age group. This leaves women with BRCA1 mutations aged 35-54 as the group most likely to benefit from MRI while taking cost into account.
MRI is also being utilized for screening of both the ipsilateral and contralateral breasts in women recently diagnosed with breast cancer. The prevalence of synchronous MRI detected breast cancer is considered to be between 1 and 9.5 percent, and these cancers are often both mammographically and clinically occult.(15,16) As is the case with standard breast cancer screening, the false positive rate is high due to limited specificity.
Current evidence suggests that MRI can benefit women at high risk, while there is much weaker evidence supporting its use in women of normal risk. Further research is necessary to develop the best method to improve screening in women at an intermediate level of risk, in whom the benefit of MRI remains unclear.
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