The FaMRIsc trial was designed to compare MRI and mammography screening in women with familial risk but no known specific driver mutation.
Annual screening with MRI detected more breast cancers and at an earlier stage than mammography in women with familial risk but no known specific driver mutation, according to a randomized trial. The increased diagnoses may come at the expense of increased false positives, however.
“Approximately 15% of all breast cancers occur in women with a family history of breast cancer (familial risk) in whom no causative hereditary gene mutation has been found,” wrote study authors led by Sepideh Saadatmand, MD, of Erasmus University Medical Center in Rotterdam, the Netherlands. “These women are at greater risk for breast cancer at a relatively young age.”
The FaMRIsc trial was designed to compare MRI and mammography screening in this population of women; it included a total of 1,355 women randomized to undergo either annual MRI along with clinical breast examination and biennial mammography (675 women) or annual mammography and clinical breast examination (680 women). Another 231 women did not consent to randomization but registered for the trial by agreeing to follow one of the two protocols; 218 of those registered for the mammography group and 18 registered for the MRI group. The results of the study were published in Lancet Oncology.
Women in the trial had a mean age of 44.7 years, and about three-quarters were premenopausal. They underwent a mean of 4.3 screening rounds.
Among the randomly allocated patients, a total of 40 breast cancers were detected in the MRI group and 15 were detected in the mammography group (P = .0017). Among invasive cancers (24 in the MRI group and 8 in the mammography group), the median size was smaller with MRI, at 9 mm compared with 17 mm (P = .010). They were also less frequently node-positive, at 17% compared with 63% in the mammography group.
MRI also resulted in cancer detection at an earlier stage than mammography, with 48% of those in the MRI group detected at stage T1a or T1b, compared with only 7% of those in the mammography group. Only one cancer found in the MRI group was stage T2 or higher (4%), compared with 13% of the mammography group (P = .035).
There were more false positives with MRI, totaling 449 compared with 276 in the mammography group (P < .001). The incidence of false positives was 159.7 per 1,000 screening rounds with MRI, compared with 89.8 per 1,000 rounds with mammography. The sensitivity of MRI was higher, though its specificity was significantly lower than mammography.
“We conclude that in real-life practice, MRI screening can result in an important and favorable shift in tumor stage at time of breast cancer detection compared with mammography screening, reducing the incidence of late-stage cancers and thus reducing the need for adjuvant chemotherapy and the risk of mortality,” the authors wrote.
In an accompanying editorial, Christiane K. Kuhl, MD, of University Hospital Aachen in Germany, called the results “compelling,” and noted that this was the first study comparing the approaches that used a randomized design. “In view of the devastating consequences of a late diagnosis of cancer, avoiding underdiagnosis should be deemed more important than avoiding overdiagnosis,” she wrote. “Rather than assuming that most additional cancers detected in the MRI group reflect overdiagnosis until proven otherwise, we should assume that not detecting these cancers by mammographic screening leads to harm.”