JCO: MRI can distinguish between BRCA1, BRCA2 carriers--guideline update?
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| Breast MRI Navigation software Image source: Sentinelle Medical |
Early diagnosis of breast cancer by intensive surveillance could reduce risk of breast cancer death in the high-risk population, which includes carriers of the BRCA1 and BRCA2 genes and those with a familial predisposition. Studies have indicated that MRI is twice as sensitive as mammography in this population. However, the breast imaging community has not reached consensus on screening protocols for various risk groups.
Dutch researchers revisited the large-scale MRI Screening Study (MRISC), a nonrandomized prospective cohort study that enrolled 2,275 high-risk women between Nov. 1, 1999 and March 1, 2006, to assess potential differences between BRCA1 and BRCA2 mutation carriers.
This study included 2,157 participants from ages 25 to 75 years who were divided into four groups: carriers of BRCA1, BRCA2 or other mutations; a high-risk group with 30 to 50 percent cumulative lifetime risk (CLTR) and a moderate-risk group with 15 to 30 percent CTLR. Women were screened with biannual clinical breast examination (CBE) and annual mammography and MRI.
Researchers defined a positive mammography or MRI based on BI-RADS score 3, 0, 4 or 5 and an uncertain or suspicious CBE. Carcinomas detected by women between screening were defined as interval cancers. Overall cancer rates were calculated as the total numbers of breast cancers, including ductal carcinoma in situ (DCIS), per 1,000 women-years at risk, explained the research team led by Adriana J. Rijnsburger, MD, of Erasmus Medical Center in Rotterdam, the Netherlands.
By March 1, 2006, 98 tumors were detected in 94 women; 80 percent of the breast cancers were invasive, and 20 percent were DCIS. BRCA2 carriers had the highest rate of detection at 39.2 per 1,000 woman-years while the overall detection was 10.4 per 1,000 woman-years.
Researchers reviewed data for the 75 breast cancers with results of both mammography and MRI and found that 43 percent were detected only by MRI, 25 percent were detected by both MRI and mammography and 16 percent by mammography alone. Four percent were detected only by CBE. Sensitivity was 70.7 percent for MRI, 41.3 percent for mammography and 20.6 percent for CBE, with the difference between mammography and MRI reaching statistical significance.
The authors noted mammographic sensitivity of 25 percent for BRCA1 carriers and 61.5 percent for BRCA2 carriers, which can be partially attributed to the higher proportion of DCIS in BRCA2 carriers and the relatively better performance of mammography with DCIS versus invasive tumors in this study. In contrast, MRI yielded a sensitivity of 66.7 percent for the BRCA1 subgroup and 69.2 for the BRCA2 group.
The study team reported additional differences between BRCA1 and BRCA2 carriers with the BRCA1 group showing a higher proportion of interval cancer, a nonsignificantly lower proportion of DCIS and a significantly greater frequency of unfavorable tumor size at diagnosis. “Most strikingly, BRCA1-associated tumors behave completely differently from BRCA2-asscoiated tumors and those from other risk groups,” stated the researchers, who suggested that a modified screening schedule for BRCA1 carriers or application of specific treatment regimens or preventive measure may be necessary to further improve survival in women with the BRCA1mutation.
Overall, the 43 percent MRI detection rate, “in combination with the detection of a favorable tumor stage support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20 to 25 percent or greater CLTR of breast cancer due to familial predisposition,” concluded the researchers.