Letter to the Editor: “A change in paradigm of breast cancer screening in European women with extremely dense breasts”

by Athina Vourtsis, Wendie A. Berg, on behalf of DenseBreast-info.org (vourtsis@mammography.gr )

Breast cancer screening in women with extremely dense breasts recommendations of the European Society of Breast Imaging (EUSOBI)

To the Editor-in-Chief,

We congratulate the European Society of Breast Imaging (EUSOBI) for the recent recommendations on screening women with extremely dense breasts with contrast-enhanced magnetic resonance imaging (MRI) every 2-4 years between the ages of 50 to 70 years or, when MRI cannot be applied, breast ultrasound combined with mammography [1]. We warmly endorse the EUSOBI recommendation to inform all women in Europe of their breast density in the setting of this action.

After striving for many years for the rights of women to be equitably engaged in breast cancer awareness, knowledge and communication, we are delighted to welcome those recommendations [1]. Since 2015, DenseBreast-info.org (DB-I), and subsequently since 2018, DB-I/Europe [2], have been providing educational tools to radiologists/health professionals, as well as information to women, on the implications of breast density and the effectiveness of supplemental screening in women with dense breasts. This medically-sourced website is the collaborative effort of world-renowned breast imaging experts and medical reviewers from 21 European countries, and includes European-specific content from European Supporters and a Continuing Medical Education (CME/CE) opportunity, entitled “Dense Breasts and Supplemental Screening”. Organizations linking to DenseBreast-info.org resources include the European Society of Radiology (Patient Advisory Group, Vienna), the Royal College of Radiologists, the European Federation of Radiographer Societies, the Society/College of Radiographers (UK), the International Control Partnership Portal, ecancer.org and the leading research charity, Prevent Breast Cancer.

Among available modalities for supplemental screening in women with dense breasts, contrast-enhanced MRI has shown the highest incremental cancer detection rate (CDR, 16.0 per 1000 women screened) after a negative 2D mammography [3]. Notably, the randomized DENSE trial [4] demonstrated that contrast-enhanced breast MRI significantly improved breast cancer detection in women with extremely dense breasts and provided the evidence supporting the EUSOBI recommendations. To objectively distinguish extremely dense from heterogeneously dense breasts, the DENSE trial used quantitative density assessment (Volpara Health Technologies, Wellington, New Zealand).

Further guidance is needed for the screening of women with heterogeneously dense breasts, since they also have high risk of a false negative mammogram and of experiencing diagnosis of a symptomatic interval cancer despite participation in mammographic screening. There is a 5.6-fold (95% CI: 2.1 to 15.3) increased risk of interval cancer in women with heterogeneously dense breasts versus women with fatty breasts [5]. The results from the EA1141 study, which notably analyzed women with heterogeneously dense breasts as a majority (77% of the total sample), showed a significantly higher rate of breast cancer detection with abbreviated breast MRI versus DBT, suggesting that MRI is effective as a standalone exam in screening women with heterogeneously dense breasts [6]; therefore, the evaluation of cost-effectiveness for abbreviated MRI in this group of women should be a research priority, in view of the promising findings.

Long-term population screening with contrast-enhanced MRI raises concerns for accumulation of gadolinium in the brain after repeated MRI examinations [7]. Although gadolinium deposition is unlikely to be problematic [8,9], long-term implications, if any, have not yet been reported [10].

Both hand-held ultrasound (HHUS) and automated breast ultrasound (AUS) have shown to improve breast cancer detection in women with dense breasts when added to mammography with an incremental CDR of 2.0-2.7 per 1000 women screened [3,11]. Although both techniques have comparable performance, AUS provides reproducible wide field of view in an axial volumetric acquisition, where nearly the entire breast is depicted on the coronal plane, whereas HHUS allows characterization of vascularity and elasticity. There is a need for standardized training in hand-held and automated options of breast ultrasound regarding performance and interpretation [12]. Contrast-enhanced mammography (CEM) has also shown overall promising results with an incremental CDR equal to 10.7 per 1000 women screened beyond 2D mammography [3].

In addition to breast density, other risk factors, such as obesity, personal history of breast cancer, LCIS, and hormonal factors should be taken into consideration in future studies and optimization of screening algorithms in the era of precision screening.