Examining the effectiveness of supplementary imaging modalities for breast cancer screening in women with dense breasts: A systematic review and meta-analysis
Introduction
Many countries have implemented mammography screening programs to decrease breast cancer mortality via early diagnosis [1], [2]. In mammography screening, identifying breast cancer in the denser breast has been highlighted as an area of concern for several years [3]. The American College of Radiology Breast Imaging-Reporting and Data System [BI-RADS] [4] categorises levels of breast density. It employs the letters ‘a’ to ‘d’, where ‘a’ refers to breasts which are almost entirely fatty, ‘b’ refers to breasts which have scattered areas of fibro-glandular density, ‘c’ is defined as breasts that are heterogeneously dense and ‘d’ refers to extremely dense breasts. Recently the European Society of Breast Imaging (EUSOBI) guidelines recommend women should be appropriately informed about their breast density and that supplemental screening should be in place for women with extremely dense breasts [78].
Women with either heterogeneously or extremely dense breast tissue can be classified as having high mammographic density. High mammographic breast density decreases the sensitivity of full-field digital mammography [FFDM] to around 47% due to its masking effect. It can increase false positives owing to the superimposition of the dense parenchymal patterns [5]. Given that women with dense breasts experience reduced sensitivity with FFDM, imaging modalities, namely Digital Breast Tomosynthesis [DBT], Magnetic Resonance Imaging [MRI], Hand-held Ultrasound [HHUS], Automated Breast Ultrasound [ABUS], Contrast-enhanced Digital Mammography [CEDM] and Molecular Breast Imaging [MBI], have been introduced as supplemental screening to FFDM [6], [7], [8]. Published results within the last ten years [2011–2021] have demonstrated improved breast cancer detection and decreased interval cancer rates associated with the introduction of supplemental screening for dense breasts [9], [10], [11].
Systematic reviews have examined the role of individual supplementary imaging modalities such as HHUS or DBT [12], [13]. In addition, Melnikow and colleagues [14] evaluated the diagnostic test performance and clinical results of supplementary screening with HHUS, ABUS, MRI and DBT [14]. Another systematic review and meta-analysis by Scaranelo and colleagues [15] was ‘ongoing’ at the time of writing. Furthermore, the revised European Breast Guidelines [16] was informed by systematic reviews of the evidence conducted between March 2016 and December 2018.
Since previous systematic reviews [14], [16] did not include CEDM or MBI as supplementary screening, the purpose of the current systematic review was to build on existing systematic reviews and include CEDM and MBI. The current systematic review also builds on the existing knowledge gained from previous systematic reviews as it includes both prevalent screens and incident screens. Moreover, the field of breast imaging is a rapidly evolving one with new imaging modalities such as CEDM, MBI and ABUS which supports the need for an updated systematic review of the literature in the field with the aim to evaluate supplementary imaging modalities for breast cancer screening in women with dense breasts.
Section snippets
Protocol registration
The review protocol was registered in PROSPERO [17] [registration number CRD42019145308].
Eligibility criteria
A set of criteria for inclusion and exclusion of studies were set beforehand on the understanding of the literature as per PRISMA guidelines [Table 1] [18].
For retrieved studies to be included in the systematic review, the studies had to include asymptomatic women with dense breasts BI-RADS c or d; prospective or retrospective observational studies, randomised controlled trials or diagnostic test accuracy
Search results
A total of 3764 studies were eligible for a title and abstract screening, and 221 studies were checked at full-text reading [Fig. 1]. Forty-two met the predefined inclusion criteria and were included in the qualitative synthesis; study inclusion with reasons for exclusion are described in Fig. 1.
The review team identified and reviewed studies of diagnostic test characteristics with HHUS, ABUS, MRI, DBT, MBI and CEDM among women with dense breasts and negative screening mammography. Twenty-one
Main findings
The findings from this systematic review are consistent with previous studies [7], [12], [13] that indicate that supplementary screening among women with dense breasts and recent negative mammography can consistently identify additional cancers and lead to further recalls and biopsies. Based on the meta-analysis, the sensitivity of supplementary imaging examinations was 89% and specificity 91%. The highest breast cancer detection rate was with MRI [33.5 per 1000 women] (Appendix A) [55]. Recall
Conclusion
While further research is required to focus on women with dense breasts as their only risk factor, supplementary imaging is beneficial for women with dense breasts. The highest breast cancer detection rate and biopsy rate in women with dense breasts were associated with supplemental MRI. The highest recall rate was associated with HHUS.
Funding Sources
This work is part of a PhD programme which is part-financed by the Tertiary Education Scholarship Scheme [TESS], Government of Malta [TESS Contract MEDE 417/2018/61]. The primary author would like to thank the TESS for the financial support covering the University of Salford fees. The funding source was not involved in the review.
Acknowledgements
Special thanks go to Prof Alison Brettle and Ms Nicole Grech for their support throughout this systematic review article.
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