Supplemental MRI Screening for Women with Extremely Dense Breast Tissue

SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 268,600 new cases of invasive breast cancer will be diagnosed in 2019 and about 41,760 women will die of the disease. Screening mammography complemented by breast self exam and clinical breast exam has resulted in early detection of breast cancer and successful outcomes. Even though mammography is a sensitive screening test, a small percentage of breast cancers may not show up on mammograms but may be palpable on examination by the patient or the clinician. Further, mammograms are less likely to find breast tumors in younger women with dense breast tissue. A breast Magnetic Resonance Imaging (MRI) is more sensitive than mammography although the specificity of a breast MRI is lower, resulting in a higher rate of false-positive findings and potentially unnecessary biopsies. Microcalcifications in the breast can be missed by a breast MRI. Taking these factors into consideration, appropriate utilization of breast MRI becomes relevant.

The American Cancer Society (ACS) recommends an annual MRI as an adjunct to screening mammogram and clinical breast exam in certain groups with increased risk of breast cancer. In a study published by Stout NK, et al., (JAMA Intern Med. 2014;174:114-121), it was noted that breast MRI was over utilized in those who did not fit the ACS criteria and was under utilized in those with documented genetic mutations. Routine breast MRI screening is not recommended for a new breast cancer diagnosis or for breast cancer surveillance and should only be considered for the group of individuals who have the most benefit. Breast MRI is performed preferably between days 7-15 of menstrual cycle for premenopausal women, using a dedicated breast coil, with the ability to perform a biopsy under MRI guidance by experienced radiologists, during the same visit.

DENSE trial is a multicenter, randomized, controlled study which evaluated the effect of supplemental Magnetic Resonance Imaging (MRI) on the incidence of interval cancers, in women with extremely dense breast tissue. In this trial, 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography were randomly assigned in a 1:4 ratio to a group that was invited to undergo supplemental MRI (N=8061) or to a group that received mammography screening alone (N=32,312). Of the women who were invited to undergo MRI, 59% accepted the invitation (N=4783). All MRI examinations were performed with the use of a dedicated bilateral breast coil. The Primary endpoint was the difference in the incidence of interval cancers during a 2-year screening period, between the mammography screening-only group and MRI-invitation group. Secondary endpoints included the recall rate for additional examination, the cancer-detection rate on MRI, the false positive rate, the positive predictive value, and tumor characteristics.

The interval cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group (P<0.001). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings. The Positive Predictive Value of a positive MRI result was 17.4%, the Positive Predictive Value of an indication for biopsy was 23.9% and the Positive Predictive Value of a biopsy was 26.3%. The false positive rate was 79.8 per 1000 screenings. As a result of the MRI screening, 300 women underwent a breast biopsy and of these women, breast cancer was diagnosed in 79 women, of whom 64 had invasive breast cancer and 15 were diagnosed with DCIS.

The authors concluded that the use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone, during a 2-year screening period. Whether a reduction in interval cancers is an appropriate surrogate for improved Overall Survival, remains unclear. Supplemental MRI Screening for Women with Extremely Dense Breast Tissue. Bakker MF, de Lange SV, Pijnappel RM, et al. for the DENSE Trial Study Group. N Engl J Med 2019; 381:2091-2102