MRI versus Mammography plus Ultrasound in Women at Intermediate Breast Cancer Risk: Study Design and Protocol of the MRIB Multicenter, Randomized, Controlled Trial

Luigina Bonelli ,Simona Tosto,Claudio Losio,Massimo Calabrese,Giovanna Trecate,Lucia Camera,Chiara Zuiani,Stefano Corcione,Antonella Petrillo,Simone Schiaffino,Andrea Cozzi,Licia Gristina,Paolo Belli,Stefania Montemezzi,Francesco Sardanelli,Ilaria Poirè,Sara Viganò,Rubina Manuela Trimboli,Francesca Valdora,Marta Panzeri,Daniele De Falco Alfano,Federica Pediconi,Luca A Carbonaro

doi:10.3390/diagnostics11091635

Abstract

In women at high/intermediate lifetime risk of breast cancer (BC-LTR), contrast-enhanced magnetic resonance imaging (MRI) added to mammography ± ultrasound (MX ± US) increases sensitivity but decreases specificity. Screening with MRI alone is an alternative and potentially more cost-effective strategy. Here, we describe the study protocol and the characteristics of enrolled patients for MRIB feasibility, multicenter, randomized, controlled trial, which aims to compare MRI alone versus MX+US in women at intermediate breast cancer risk (aged 40–59, with a 15–30% BC-LTR and/or extremely dense breasts). Two screening rounds per woman were planned in ten centers experienced in MRI screening, the primary endpoint being the rate of cancers detected in the 2 arms after 5 years of follow-up. From July 2013 to November 2015, 1254 women (mean age 47 years) were enrolled: 624 were assigned to MX+US and 630 to MRI. Most of them were aged below 50 (72%) and premenopausal (45%), and 52% used oral contraceptives. Among postmenopausal women, 15% had used hormone replacement therapy. Breast and/or ovarian cancer in mothers and/or sisters were reported by 37% of enrolled women, 79% had extremely dense breasts, and 41% had a 15–30% BC-LTR. The distribution of the major determinants of breast cancer risk profiles (breast density and family history of breast and ovarian cancer) of enrolled women varied across centers.

Highlights

Mammography (MX) represents the primary screening tool for breast cancer, but its preventive impact is not fully satisfactory
Our study focused on intermediate-risk women aged 40–59 years, only partially targeted by organized screening programs
Regarding breast magnetic resonance imaging (MRI) screening uptake, Berg et al [36] reported that over 40% of women at high breast cancer risk refused to undergo additional MRI screening; a similar result was observed in the DENSE trial [24]; as for the cost–benefit analysis, new studies with larger temporal horizons have recently highlighted a better outlook [37,38], which could be reinforced by the introduction of abbreviated protocols reducing acquisition and interpretation times, known to match the accuracy of full protocols [39,40,41]

Summary

Introduction

Mammography (MX) represents the primary screening tool for breast cancer, but its preventive impact is not fully satisfactory. Considering the screening age range, MX yields an estimated breast cancer mortality reduction of about 30% in the target population, with a beneficial effect persisting for at least 10 years [1,2]. Even for women who regularly adhere to a screening program, risk reduction brought about by MX screening remains approximately 40% [3]. Such limited efficacy has been attributed to both the intrinsic limitations of MX and the highly variable biological characteristics of breast cancer [4], as well as to women’s individual characteristics such as age and breast density (BD). Contrast-enhanced magnetic resonance imaging (MRI), and contrast-enhanced mammography may all display increased sensitivity, compared to MX, especially for small breast cancers [10,11,12], a more sensitive test could detect more small tumors only because they are growing slowly, potentially leading to an increase in overdiagnosis [13]

Methods

Findings

Discussion

Conclusion