MRI screening led to lower rate of interval cancers in women with dense breasts
While following a negative mammogram with MRI screening halved the risk of interval cancer in women with dense breast tissue, the impact on survival remains unclear, an editorial said.
Supplemental MRI screening in women with dense breasts led to significantly fewer diagnoses of interval breast cancer over a two-year period, although most of the resulting biopsies did not lead to a cancer diagnosis, a randomized trial found.
From December 2011 through November 2015, researchers enrolled women ages 50 to 75 years in the Netherlands with extremely dense breast tissue (defined as grade 4 density as measured on imaging software) and normal results on mammography who were participating in the national population-based screening program. They randomly assigned 8,061 women to be invited to have additional MRI screening and 32,312 to receive mammography only. Of the women who were invited to have MRI screening, 4,783 (59%) accepted. The primary outcome was the difference between groups in the incidence of interval cancer during a two-year screening period. Secondary outcomes included the recall rate for additional examination, the cancer-detection rate on MRI, the false-positive rate, and the positive predictive value. The trial was funded primarily by University Medical Center Utrecht and governmental and philanthropic organizations, with some support by Bayer Pharmaceuticals and an in-kind contribution by Volpara Health Technologies, the manufacturer of the imaging software. The study design, data gathering and analysis, and manuscript production were the responsibility of the authors independent of funding source except for University Medical Center Utrecht. Results were published on Nov. 28 by the New England Journal of Medicine.
Diagnoses of interval cancer were uncommon. Overall, the rate of interval cancer was 2.5 per 1,000 screenings in the MRI-invitation group and 5.0 per 1,000 screenings in the mammography-only group, a difference of 2.5 per 1,000 screenings (95% CI, 1.0 to 3.7; P<0.001). Of the 20 women diagnosed with interval cancer in the MRI-invitation group, four had MRI (0.8 per 1,000 screenings) and 16 did not accept the invitation (4.9 per 1,000 screenings). In the mammography-only group, interval cancer was diagnosed in 161 of 32,312 women.
Of the women who had MRI screening, nearly 10% were recalled for abnormal scans (recall rate, 94.9 per 1,000 screenings; 95% CI, 86.9 to 103.6). The cancer-detection rate with MRI was 16.5 per 1,000 screenings (95% CI, 13.3 to 20.5). Of the 300 women who had a breast biopsy as a result of the MRI screening, 221 (73.7%) did not have breast cancer, and 79 (26.3%) were diagnosed (64 with invasive breast cancer and 15 with ductal carcinoma in situ). The false-positive rate was 8.0% (79.8 per 1,000 screenings; 95% CI, 72.4 to 87.9). The positive predictive value of a positive MRI result was 17.4% (95% CI, 14.2% to 21.2%), the positive predictive value of an indication for biopsy was 23.9% (95% CI, 19.6% to 28.8%), and the positive predictive value of a biopsy was 26.3% (95% CI, 21.7% to 31.6%). Among those who had MRI screening, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening.
Among other limitations, the trial was not large enough to assess the effect of MRI screening on breast cancer-specific or overall mortality, although the lower rate of interval cancers among participants who had MRI is indicative of and a prerequisite for an effect on mortality, the authors noted. “After that, a reduction in the number of advanced cancers would also be required to show a mortality benefit, which would require several years of follow-up,” they wrote. “Thus, we are now using our results in a simulation study to evaluate the reduction in mortality and the extent of overdiagnosis, together with the effects on costs and quality of life.”
Still, it remains unclear whether the tumors would have otherwise been detected eventually or threatened patients' survival, particularly because 72 of 79 cancer diagnoses detected on supplemental MRI screening were stage 0 or I, an editorial noted. “The findings of this trial are likely to reinforce the idea that MRI screening is important in women with dense breast tissue,” the editorialist wrote. “But will we be putting these women at increased risk of procedures without contributing to their eventual survival?”