Biannual MRI outperformed annual mammography in the early detection of invasive breast cancer among a cohort of genomically stratified high-risk women, according to study results.
“This is the first report on a prospective cohort of genetically defined high-risk women undergoing intensive surveillance with MRI every 6 months in conjunction with clinical breast examinations and annual mammography,” Rodrigo Santa Guindalini, MD, of the Center for Clinical Cancer Genetics and Global Health at The University of Chicago, and colleagues wrote. “For these patients, annual mammography did not provide any additional benefit to biannual dynamic contrast-enhanced MRI scans.”
The researchers established a novel imaging surveillance program between 2004 and 2016 to evaluate the performance of biannual dynamic contrast-enhanced MRI in combination with annual mammography among 295 women (mean age, 43.3 years) undergoing surveillance for breast cancer. Women had a 20% or more lifetime risk for breast cancer and/or a known genetic mutation.
The researchers additionally sequenced genomic DNA for 11 genes known to be associated with an inherited predisposition to breast cancer. Fifty-three percent of women had at least one genetic mutation, including 75 with BRCA1 and 61 with BRCA2 mutations.
Overall, the population underwent 2,111 MRIs (mean, 7.3 per woman) and 1,223 mammograms (mean, 4.3 per woman).
Screening led to diagnoses of 13 early-stage invasive cancers and four ductal carcinomas in situ; 15 of these occurred among women who harbored mutations.
The median invasive tumor size was 0.61 cm. No patients had lymph node metastasis at time of diagnosis and no interval invasive cancers occurred, according to the researchers.
MRI alone detected eight invasive cancers and one ductal carcinoma in situ. Mammography detected one ductal carcinoma in situ was detected only by mammography. Five invasive cancers and one ductal carcinoma in situ were detected by both screening modalities.
MRI missed one high-grade DCIS in a BRCA1 mutation carrier measuring 0.5 cm that mammography detected, as well as one intermediate-grade DCIS measuring 1.7 cm that was found incidentally in a prophylactic mastectomy specimen from a 36-year-old BRCA2 mutation carrier.
Sensitivity was 88.2% (95% CI, 63.6-98.5) with biannual MRI alone compared with 94.1% (95% CI, 71.3-99.9) with annual mammography plus biannual MRI. Sensitivity of annual mammography alone was 41.2%, (95% CI, 18.4-67.1).
The cancer detection rate was 0.7% per 100 screening episodes for each screening modality, indicating the addition of mammography to MRI did not enhance the cancer detection rate.
During a median follow-up of 3.1 years, the overall rate for breast cancer was 1.42 (95% CI, 0.83-2.27) per 100 person-years.
Eleven breast cancers were diagnosed in women with a BRCA1 mutation, yielding an incidence rate of 3.65 (95% CI, 1.82-6.53) per 100 person-years. This was significantly higher when compared with women without BRCA1 mutations (P = .0005).
Three breast cancers were detected in women with BRCA2 mutations and in one with a CDH1 mutation.
The researchers noted limitations of the study, including the relatively small number of events and the nonrandomized, single-institution design of the trial.
“Nonetheless, this genomic and imaging biomarker-rich study provides the framework for optimizing screening for early detection and cancer interception in high-risk populations,” the researchers wrote. – by Jennifer Southall
Disclosures: The study was supported by the Breast Cancer Research Foundation, Housewares Charity Foundation, NCI, Ralph and Marian Falk Medical Research Trust, and Susan G. Komen for the Cure. Please see the full study for a list of all authors’ relevant financial disclosures.