Performance Measures of Magnetic Resonance Imaging Plus Mammography in the High Risk Ontario Breast Screening Program

Anna M. Chiarelli; Kristina M. Blackmore; Derek Muradali; Susan J. Done; Vicky Majpruz; Ashini Weerasinghe; Lucia Mirea; Andrea Eisen; Linda Rabeneck; Ellen Warner

Disclosures

J Natl Cancer Inst. 2020;112(2):136-144. 

In This Article

Abstract and Introduction

Abstract

Background: The Ontario Breast Screening Program expanded in July 2011 to screen high-risk women age 30–69 years with annual magnetic resonance imaging (MRI) and digital mammography. This study examined the benefits of screening with mammography and MRI by age and risk criteria.

Methods: This prospective cohort study included 8782 women age 30–69 years referred to the High Risk Ontario Breast Screening Program from July 2011 to June 2015, with final results to December 2016. Cancer detection rates, sensitivity, and specificity of MRI and mammography combined were compared with each modality individually within risk groups stratified by age using generalized estimating equation models. Prognostic features of screen-detected breast cancers were compared by modality using Fisher exact test. All P values are two-sided.

Results: Among 20 053 screening episodes, there were 280 screen-detected breast cancers (cancer detection rate = 14.0 per 1000, 95% confidence interval [CI] = 12.4 to 15.7). The sensitivity of mammography was statistically significantly lower than that of MRI plus mammography (40.8%, 95% CI = 29.3% to 53.5% vs 96.0%, 95% CI = 92.2% to 98.0%, P < .001). In mutation carriers age 30–39 years, sensitivity of the combination was comparable with MRI alone (100.0% vs 96.8%, 95% CI = 79.2% to 100.0%, P = .99) but with statistically significantly decreased specificity (78.0%, 95% CI = 74.7% to 80.9% vs 86.2%, 95% CI = 83.5% to 88.5%, P < .001). In women age 50–69 years, combining MRI and mammography statistically significantly increased sensitivity compared with MRI alone (96.3%, 95% CI = 90.6% to 98.6% vs 90.9%, 95% CI = 83.6% to 95.1%, P = .02), with a small but statistically significant decrease in specificity (84.2%, 95% CI = 83.1% to 85.2% vs 90.0%, 95% CI = 89.2% to 90.9%, P < .001).

Conclusions: Screening high risk women age 30–39 years with annual MRI only may be sufficient for cancer detection and should be evaluated further, particularly for mutation carriers. Among women age 50–69 years, detection is most effective when mammography is included with annual MRI.

Introduction

Women who have inherited a highly penetrant breast cancer predisposition gene have an elevated lifetime risk of breast cancer compared with the general population. Among BRCA1/2 mutation carriers, the cumulative risk of developing breast cancer by age 70 years is 45% to 87%,[1–3] and at an earlier age.[4] Women with a strong family history of breast cancer or who have undergone therapeutic chest radiation before age 30 years are also at comparable increased risk.[5–9]

Several observational studies have demonstrated that women at high risk for breast cancer based on their family history and/or genetic testing benefit from screening with breast magnetic resonance imaging (MRI) in addition to mammography.[10–21] The combined sensitivity of MRI and mammography ranged from 90% to 100%, with breast cancers detected at a much earlier stage than with mammography alone in the same population.[11,13,17,19,21]

Expert guidelines recommend that women with a lifetime breast cancer risk of 20% or greater[22–25] or a history of chest radiation therapy[26] begin annual screening with MRI and mammography at age 25–30 years. However, it is unknown whether the performance of MRI screening in previous observational studies or academic centers can also be achieved in a community setting. Uncertainties also exist regarding whether recommendations for high-risk women should be individualized dependent on their age and/or risk criteria. Some groups have reported a higher interval cancer rate in younger women with BRCA1 mutations[18] and have suggested that MRI screening every 6 months might be more appropriate. The National Institute for Health and Care Excellence guidelines recommend annual MRI screening of high-risk women primarily from age 30–49 years.[27] The value of adding mammography to MRI for women younger than 40 years has also been questioned given the higher breast density and lower sensitivity of mammography in this age group,[17] particularly for BRCA1/2 mutation carriers[28,29] and women with a strong familial breast cancer risk.[30] Recent studies among women with prior chest radiation therapy have reported an improvement in screening sensitivity with the addition of mammography to MRI,[31–34] with minimal decrease in specificity.[32]

Based on recommendations from the Ontario Program in Evidence-Based Care[25] and the Ontario Health Technology Advisory Committee,[35] the Ontario Breast Screening Program (OBSP) expanded its services in 2011 to include annual MRI in addition to digital mammography for high-risk women age 30–69 years.[36] Follow-up of this large cohort screened at 30 centers across the province provides a unique opportunity to examine the benefits and harms of the combination of mammography and MRI within a population-based screening program. Because all women are screened both with MRI and mammography, performance measures can be compared with each individually within risk groups stratified by age. Prognostic features of screen-detected cancers were also compared by modality.

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