Open Access Highly Accessed Study protocol

Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc): a multicentre randomized controlled trial

Sepideh Saadatmand1*, Emiel J T Rutgers2, RobAEM Tollenaar3, Hermien M Zonderland4, MargreetGEM Ausems5, KristienBMI Keymeulen6, Margreet S Schlooz-Vries7, Linetta B Koppert1, Eveline A M Heijnsdijk8, Caroline Seynaeve9, Cees Verhoef1, Jan C Oosterwijk10, Inge-Marie Obdeijn11, Harry J de Koning8 and Madeleine M A Tilanus-Linthorst1

Author Affiliations

1 Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands

2 Department of Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands

3 Department of Surgery, Leiden University Medical Centre, Leiden, Netherlands

4 Department of Radiology, Academic Medical Centre, Amsterdam, Netherlands

5 Department of Medical Genetics, University Medical Centre, Utrecht, Netherlands

6 Department of Surgery, Academic Hospital, Maastricht, Netherlands

7 Department of Surgery, Radboud University, Nijmegen, Netherlands

8 Department of Public Health, Erasmus University Medical Centre, Rotterdam, Netherlands

9 Department of Medical Oncology, Erasmus University Medical Centre-Daniel den Hoed Cancer Centre, Rotterdam, Netherlands

10 Department of Genetics, University of Groningen, UMCG, Groningen, Netherlands

11 Department of Radiology, Erasmus University Medical Centre, Rotterdam, Netherlands

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BMC Cancer 2012, 12:440  doi:10.1186/1471-2407-12-440

Published: 2 October 2012

Abstract

Background

To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test.

The aim of the Familial MRI Screening Study (FaMRIsc) is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density.

Methods/Design

This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1) has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30–55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000), and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000).

Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor.

Discussion

Personalized breast cancer screening might optimize mortality reduction with less over diagnosis. Breast density may be a key discriminator for selecting the optimal screening strategy for women < 55 years with familial breast cancer risk; mammography or MRI. These issues are addressed in the FaMRIsc study including high risk women due to a familial predisposition.

Trial registration

Netherland Trial Register NTR2789

Keywords:
Breast cancer; Familial risk; Screening; MRI; Breast density; Cost-effectiveness