Abstract
In the mid-1990s, the identification of BRCA1/2 genes for breast cancer susceptibility led to testing breast MRI accuracy in screening women at increased risk. From 2000 onwards, ten intraindividual comparative studies showed the marked superiority of MRI: the sensitivity ranged 25−58% for mammography, 33−52% for ultrasound, 48−67% for mammography plus ultrasound, and 71−100% for MRI; specificity 93–100%, 91–98%, 89–98%, and 81–98%, respectively. Based on the available evidence, in 2006–2007, the UK National Institute for Clinical Excellence and the American Cancer Society recommended MRI screening of high-risk women, followed by other international guidelines. Despite evidence-based medicine ideally requiring randomised controlled trials (RCTs) for policy changes regarding screening procedures, breast MRI for high-risk screening was adopted in many countries worldwide. In 2019, the results of the “DENSE” RCT were published in favour of breast MRI screening of women with extremely dense breasts compared to mammography alone, showing a reduction of more than 80% of the interval cancer rate in women who attended MRI screening. Even though international recommendations in favour of this practice were issued, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts. A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have this level-1 evidence for the same procedure, we fail to do so. This critical review tries to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.
Critical relevance statement The high-level evidence in favour of breast MRI screening of women with extremely dense breasts is failing to persuade policy makers to translate this into clinical practice.
Key points
• Breast MRI screening of high-risk women was adopted on basis of the evidence provided by test accuracy comparative studies showing an MRI performance greatly superior to that of mammography.
• Breast MRI screening of women with extremely dense breasts has not been adopted although the evidence of a large reduction in interval cancer rate from a RCT.
• We illustrate the differences between the two cases, as an example of the complex ways of translation of radiological research in clinical practice according to the EBM theory.
Graphical Abstract
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Find the latest articles, discoveries, and news in related topics.Introduction
Breast cancer (BC) was explored with nuclear magnetic resonance (NMR) before its evolution into magnetic resonance imaging (MRI): in 1978, Goldsmith et al. [1] showed a significant difference in NMR relaxation times between benign and malignant breast tissues. In the 1970s, authors were thinking about NMR as a support system for pathologists. However, MRI became clinically available in 1981 and a revolution happened in the entire world of medical imaging.
Throughout the early 1980s, researchers explored the potential of breast MRI using the simple sequences available in those days [2,3,4] without injection of any contrast agent. Results were disappointing due to the large overlap of T1, T2, and proton-density values of normal and pathological tissues as well as of benign and malignant neoplasms, with the exception of normal fat and serous cysts. With the intravenous administration of a linear gadolinium-based contrast agent (the first one available, i.e. gadopentetate dimeglumine) Heywang et al. [5] began to appreciate the contrast biodistribution in breast tissues through T1-weighted images in a small group of 20 patients. The abstract states “All carcinomas enhanced, whereas dysplastic tissue enhanced slightly or not at all. […]. MR imaging of breast using Gd-DTPA may be helpful for the evaluation of dense breasts and the differentiation of dysplasia and scar tissue from carcinoma”. Other authors followed this pathway, among them the relevant group of Kaiser et al. [6].
During the same time period, there were technical developments of the breast MRI technique, including improved dedicated bilateral radiofrequency coils, better spatial resolution, T1-weighted dynamic sequences, temporal subtraction, and fat suppression/saturation [7]. Concurrently, a new emergent clinical demand arose for breast MRI after the identification of the role of the BRCA1 gene in breast and ovarian cancer susceptibility by Miki et al. in 1994 [8] and of BRCA2, a second BC susceptibility gene, by Wooster et al. in 1995 [9].
For researchers interested in innovations in BC care, these advances in knowledge and technology had opened a new scenario. They now could: (1) verify the diagnostic performance of MRI in a screening setting with a high BC incidence; (2) offer to women with hereditary predisposition to BC a possibility of an earlier detection than that offered by mammography. Notably, these high-risk women needed to be screened from a young age and were known to likely have dense breasts (with an obvious interplay between the two factors). As Heywang et al. had suggested in 1986 [5], breast density emerged as a relevant variable in the game among diagnostic modalities.
In this historical context, researchers started studies of MRI for screening high-risk women in several countries. From 2000 onwards, the publication of their results showed a large superiority of MRI versus mammography in terms of accuracy and sensitivity. After the pivotal recommendations from the National Institute for Clinical Excellence (NICE) – National Collaborating Centre for Primary Care, UK in 2006 [10] and from the American Cancer Society (ACS), USA, in 2007 [11], contrast-enhanced MRI was adopted in many countries as a screening tool for women with high hereditary BC predisposition. Variations in the adoption regarded non-negligible issues such as the level of risk and age range to undergo MRI screening or whether to perform mammography when MRI is negative [12]. For instance, considering the different age ranges for high-risk surveillance, the Department of Health in Australia recommends annual MRI surveillance for women under the age of 50 who are at high risk of developing BC [13]. In contrast, in the USA [14] and various European countries such as Austria [15], Germany [16], Italy [17], and Spain [18], the beginning of MRI surveillance is advised at the age of 25. Considering imaging modalities applied for high-risk screening, the guidelines for high-risk women in Australia [13] and Israel [19] recommend annual MRI alone, while other countries such as Austria [15], Belgium [20], Canada [21], Norway [22], Spain [18], the UK [23], and the USA [11] all indicate that MRI should be performed in adjunct to annual mammography.
The theory of evidence-based medicine (EBM), which was established in the 1990s in a clear theoretical framework by the group guided by D. Sackett [24], requires the results of RCTs to decide whether to adopt a screening test. This had been the case with population-based mammography screening from 50 to 70 years of age. A complete table about the levels of evidence needed for diagnostic tests, including their use for screening, is available at the website of Centre for EBM at the Oxford University, UK (https://www.cebm.ox.ac.uk/). However, the level of evidence needed to justify the practice of MRI screening of high-risk women was not discussed. One exception was a letter to the British Medical Journal by Irwig et al. in 2006, entitled “Evaluating new screening tests for breast cancer” [25], in the context of a specific debate about overdiagnosis estimated 15 years after the end of Malmö mammographic screening trial [26]. The authors [25] underlined the need of randomised controlled trials (RCTs) to assess the reduction in mortality (long-term design), to estimate overdetection/overdiagnosis (both long- and short-term design), and to compare the interval cancer rates as well as the rates of advanced cancers detected by subsequent screening rounds. In particular, they emphasised that “reducing the rate of interval cancer rates is crucial, representing the potential benefit of early detection rather than overdetection”. However, their conclusions took into account that RCTs to detect interval cancers could be considered “unnecessary or even unethical in people who are at substantially increased risk of developing cancer—for example, women at high risk of breast cancer because of gene mutations”.
This was the core of the problem: researchers did not want to randomise a BRCA1/2-mutated woman (with an individual BC lifetime risk of at least 60−70%) and risk not getting an MRI. However, on the methodological level, intraindividual sensitivity/specificity studies—those that had “cleared” breast MRI for high-risk screening by the NICE and the ACS—were theoretically a weak basis for the adoption of this screening procedure.
More than 38 years have passed since the first paper on contrast-enhanced breast MRI [5] and 16 years after the ACS recommendations for breast MRI for high-risk screening [11]. Four years ago, in 2019, unquestionable results of the “DENSE” RCT were published [27] in favour of breast MRI screening of women with extremely dense breasts, i.e. the breast density d class of the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) [28]. A reduction of more than 80% of the interval cancer rate in women who attended MRI screening versus those who did not was observed. International recommendations in favour of this practice such as those from the EUSOBI [29] were issued. However, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts.
A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have evidence from RCTs for the same procedure, we fail to do so. Even in the Netherlands, where the DENSE trial has been conducted, considerable difficulties hinder its implementation [30].
This critical review aims to spotlight this issue, trying to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.
The conceptual EBM framework of screening tests
To understand the above-mentioned EBM conceptual framework that guides the adoption of screening tests, we take into consideration the oldest example in radiology, i.e. screening mammography. In 1998, the UK National Screening Committee defined screening as the systematic application of a test to identify apparently healthy individuals at increased risk of a specific disorder, in order to offer information, further investigation, or treatment, as appropriate [31]. As recently stated by the World Health Organization, a specific target population is invited from central records to perform simple tests to detect individuals with a disease who do not yet exhibit symptoms. Furthermore, screening programmes should be implemented only after establishing their effectiveness, ensuring adequate resources, having facilities for diagnoses, as well as for treatment and follow-up, and when the prevalence of the disease justifies the costs associated with screening. Finally, screening efforts should be justified by the considerable advantages it may offer (in terms of disease secondary prevention and disability/mortality reduction), which significantly outweigh any potential negative consequence [32]. This document clearly distinguishes between “screening” as applied to apparently healthy individuals from “early diagnosis” as applied to individuals with sign or symptoms (the “clinical” or “diagnostic” context).
In fact, screening addresses disorders that, while occurring with varying frequencies in the lives of individuals, remain consistently uncommon in each screening round, leading to a low pretest probability of disease. In the case of BC screening, this probability will be higher at the first round (“prevalent” BCs, i.e. those that developed and are detectable up to that time) and lower in later rounds (“incident” BCs, i.e. the new ones). In this scenario, a test with a sufficiently high sensitivity becomes essential to avoid as many as possible missing cases. However, when sensitivity is prioritised, specificity tends to suffer as a trade-off, with an unavoidable increase in the number of false positive cases needing unnecessary invasive and/or expensive further investigations [33, 34]. This aspect may cause potential physical and psychosocial harms in the subjects attending the screening together with increased healthcare costs, to be considered when evaluating the overall cost-effectiveness of any screening programme [35,36,37].
Furthermore, in the context of cancer screening, one major drawback of highly sensitive tests lies in the risk of overdiagnosis, which arises when individuals receive diagnoses for conditions that would not become clinically relevant within their lifespan due to their biologically indolent or nonprogressive nature [38]. Interestingly, we should distinguish between “overdetection”, whose responsibility is in the hands of radiologists, and the properly called “overdiagnosis”, whose responsibility should at least be shared with pathologists [39]. Importantly, overdiagnosis can lead to adverse effects for both patients’ well-being and the healthcare system at large, including compromised quality of life and even premature mortality stemming from unnecessary treatments (overtreatment), psychosocial distress due to the inaccurate classification of individuals as patients (stigmatisation), and unwarranted costs derived from the use of healthcare resources for follow-up, treatments, and interventions [40].
Of note, the likelihood of overdiagnosis, as per its definition, is negligible in the context of “diagnostic” tests, i.e. in the clinical scenario. Thus, according to EBM, the decision of whether to administer diagnostic tests should be steered by methodically executed studies on diagnostic performance, i.e. “sensitivity and specificity” studies, involving consecutive patients. These studies should be underpinned by meticulously established clinical decision criteria and dependable reference standards. High-quality and multicentre studies provide the most robust evidence [24].
Conversely, given the heightened risk of overdiagnosis in the screening setting, the EBM principles oriented the European Council Recommendations to state that the introduction of a novel screening tool should only occur after substantiating the clinical relevance on patient outcomes via rigorously conducted RCTs, since mere improvements in sensitivity and specificity are deemed as inadequate to warrant its adoption [41,42,43].
RCTs remain the most effective approach for tackling two substantial biases that arise within screening programmes, known as “lead bias” and “length bias”. The former entails the inclination to assume greater survival outcomes solely due to the earlier diagnosis, whereas the latter pertains to the phenomenon where slower-growing tumours are more likely to be detected in screening rounds, while faster-growing ones might be missed [44,45,46,47]. As a result, focusing solely on the survival of patients who undergo a screening test might create a false impression of improvement, since slower-growing tumours identified during screening tend to stand out more compared to those that go undetected [48].
Nonetheless, the performance of screening tests should be also considered relative to other aspects of cancer management, including the effectiveness of interventions and the availability of facilities for diagnosis and treatment. Indeed, it is crucial in a screening programme to ensure access to treatments that provide advantages when administered at an early stage [49].
The case for screening mammography for the general average-risk female population
Screening mammography, in particular population-based programmes, have been established in Europe on the basis of RCTs showing clearly favourable results [50]. Only a few European countries still do not have active screening mammography programmes for women aged 50−70 [51, 52]. The Guidelines Development Group of the European Commission Initiative on Breast Cancer [53, 54] confirmed the recommendation to use organised mammography screening for the early detection of BC in asymptomatic women [55].
Indeed, in 2015, the International Agency for Cancer Research published an analysis of data from 20 cohort studies and 20 case-control studies (including RCTs) [56] affirming that women aged 50–69 who participated in mammography screening, experienced a reduction of about 40% in BC mortality. Furthermore, several studies indicated that women aged 70–74 also benefited from a noteworthy decrease in BC mortality through mammography screening. This analysis made a point [57], also regarding potential drawbacks, including the risk of false positive results as well as overdiagnosis, the latter being subject to variable estimates due to different study designs and methodologies [43].
Furthermore, as healthcare interventions evolve over time, so does the role and impact of mammographic screening compared to its initial implementation and to the first trials. This evolution is influenced by the development of more effective novel systemic therapies and heightened BC awareness, underlining the dynamic nature of healthcare strategies. Importantly, even when considering the effectiveness of new target therapies, screening mammography has been shown to still provide important advantages in terms of patient’s outcome [49].
The case for breast MRI for high-risk screening
As outlined in the Introduction, contrast-enhanced breast MRI has been recognised as a valuable screening tool in women at high BC risk. From 2000 to 2015, several studies reported a large superiority of MRI versus mammography (in some studies also versus ultrasound) in women with hereditary BC predisposition [58,59,60,61,62,63,64,65,66,67,68,69,70,71,72] (Table 1). Ten studies, 15 papers, over 6000 women enrolled, near 19,000 rounds. The sensitivity ranged 25−58% for mammography, 33−52% for ultrasound, 48−67 for mammography plus ultrasound, and 71−100% for MRI; specificity 93–100%, 91–98%, 89–98%, and 81–98%, respectively. It was a “large” body of evidence, which was already substantial in 2006−2007, when first recommendations were issued. However, those studies were solely intraindividual comparative analyses. This represented the base of evidence for recommending and adopting breast MRI for high-risk screening. No RCT was available.
It is interesting to note the wording of the ACS in the 2007 guideline [11]: “Screening MRI is recommended for women with an approximately 20–25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin disease.Footnote 1 There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography.” This guideline was issued after considering the results from the first six studies reported in Table 1, performed in Germany, Italy, The Netherlands, Canada, the USA, and the UK, available up until July 2006.
Up to August 26, 2023, according to the Scopus database, this paper [11] got 2122 citations (99th percentile), a number showing its impact on the community of BC specialists. Even though preceded by the NICE recommendations [10], this ACS guideline [11] was a game changer in the history of breast MRI. Thereafter, many other guidelines recommended MRI for screening high-risk women, including those issued by the European Society of Breast Imaging (EUSOBI) in 2008 and 2015 [73, 74], by the multidisciplinary European Society of Breast Cancer Specialists, EUSOMA, in 2010 [75] as well as those issued by the ACR in 2018 and 2023 [76, 77]. The evidence from these comparative studies also showed the erroneous “mantra” about the so-called “low specificity” of breast MRI, which had previously limited the adoption of the new technique [78]. A number of meta-analyses and cost-effective analyses confirmed the diagnostic performances of breast MRI screening in the high-risk setting [79].
Why was breast MRI high-risk screening recommended on the basis of “only” comparative test accuracy studies? Why were the EBM rules not applied? Many reasons can be taken into account [80]. First of all, the undeniable superior accuracy of breast MRI in high-risk women raised ethical concerns that made it difficult to withhold MRI from a control group, especially for solely study purposes [81]: the absolute difference in sensitivity between MRI and mammography considering the ten studies reported in Table 1 ranged from 25 to 60%. Thus, obtaining consent for randomisation was improbable among women with hereditary BC predisposition due to heightened BC awareness, particularly within families with multiple affected individuals.
RCTs assessing the efficacy of MRI for high-risk screening had not been proposed or carried out until 2019, when the results of the first RCT were published by Saadatmand et al. [82], significantly later than the widespread adoption of breast MRI for high-risk screening. From 2011 to 2017, 1355 women provided consent for randomisation (675 allocated to MRI and 680 to mammography group), and 231 women opting for registration (218 to mammography and 13 to MRI). After 4.3 mean rounds/woman, significantly more BCs were detected by MRI (n = 40) than by mammography (n = 15). The 24 invasive cancers detected by MRI (median size 9 mm) were significantly smaller than the 8 detected by mammography (median size 17 mm) and less frequently node-positive. The stage of BCs detected at incident rounds was significantly earlier and less frequently node-positive in the MRI group than in the mammography group. Of note, all 7-stage ≥ T2 tumours were in the two highest breast density ACR-BI-RADS categories (c or d).
This trial demonstrated that breast MRI screening can lead to a shift in tumour stage upon detection, thereby reducing the incidence of late-stage cancers, with a consequent decreased need for adjuvant chemotherapy and a reduction in mortality. This is an issue of particular relevance for BRCA mutation carriers due to the rapid growth of cancers and the increased occurrence of triple-negative BCs in these individuals [83, 84]. The role of MRI in the early detection of triple-negative BCs and the effect on survival in high-risk women had been already shown in the Italian HIBCRIT study [85].
Several months after the publication of the work by Saadatmand et al. [82], the German Consortium for Hereditary Breast and Ovarian Cancer published their 10-year experience of high-risk BC surveillance with MRI [16]. In a cohort of 4573 high-risk women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) and 14,142 rounds with MRI between 2006 and 2015, 221 primary BCs (185 invasive, 36 ductal carcinomas in situ [DCIS]) were diagnosed within 12 months of annual screening. Of all cancers, 86% (174/206, 15 unknown) were stage 0 or I. The sensitivity of the programme was 90%, without significant differences by risk level or age. Specificity was significantly lower in the first round (85%) than in subsequent rounds (91%). This experience showed that high-risk screening with MRI could be successfully implemented in clinical practice.
The case for breast MRI for screening in women with dense breasts
Although breast MRI screening was initially set up to target specific high-risk populations, the extension to women with dense breasts had been already explored in the first experience with contrast-enhanced breast MRI in 1985 [5] and considered as an ongoing issue by the ACS guideline in 2007 [11]. Women with dense breasts were classified as having an “intermediate risk” along with women with previous personal BC or atypical ductal hyperplasia or other lesions with uncertain malignant potential [86]. The results from the DENSE RCT [27] have drastically changed this scenario.
Breast density, which refers to the proportion of fibroglandular tissue in relation to adipose tissue [87], had been identified as an independent risk factor. Women with the densest breasts are four times more likely to develop BC compared to those with predominantly fatty breasts [87, 88]. Moreover, increased breast density masks underlying breast lesions, leading to a reduction in the sensitivity of mammography, dropping from 86–89% in predominantly fatty breasts to 62–68% in extremely dense breasts [89], leading to a high rate of “underdiagnosed” BCs. Thus, breast density represents an accessible variable for risk-adjusted screening strategies in the current era of personalised and precision medicine.
Meanwhile, since the 2000s, digital breast tomosynthesis (DBT) was proposed as a screening tool to overcome the lower mammography sensitivity in the presence of overlapping breast tissues, particularly for specific density and age groups. Cancer detection rates were shown to increase by 20–40% in women with both low- and high-density breast [90, 91], with a differential incremental detection according to breast density, meaning that the increase in cancer detection tends to be greater in high- versus low-density breasts (pooled difference in incremental cancer detection rate of 1.0 per 1000 screens) [92]. However, very limited evidence, if any, of a reduction of interval cancer rate was found [93, 94]. Therefore, DBT does not seem to solve the breast density dilemma.
The results of the DENSE trial deserve the highest attention because this is a RCT, fully compliant with the EBM rules for implementing screening tests. Women aged 50–75 who exhibited extremely dense breast tissue were invited to undergo biennial screening with breast MRI following negative screening mammography [95]. In the first round of screening [27], supplemental breast MRI led to the detection of an additional 16.5 cancers per 1000 screening examinations. A statistically significant and clinically relevant reduction in interval cancer rate versus the control arm was observed both at the intention-to-screen (2.5‰ versus 5.0‰) and at the complier average causal effect analysis (0.8‰ versus 5.1‰), indicating that supplemental MRI screening results in a strong reduction in interval cancer rate, effectively mitigating underdiagnosis. In the subsequent screening round [96], a further MRI detection rate of only 5.8 per 1000 screening examinations was reported, providing evidence that relevant cancers had already been detected by MRI; a reduction in false positive findings was also observed (Table 2).
We acknowledge that these results (i.e. over 80% reduction in interval cancer rate after the first round) are not a direct demonstration of a reduction in disease-specific mortality; however, it can be considered as one of the best proxy parameters of effectiveness of a screening test in the framework of EBM [25].
Interestingly, a further analysis of data from the first round [98] showed that a prediction model based on all clinical characteristics and MRI findings could have prevented 46% of false-positive recalls and 21% of benign biopsies, without missing any cancers.
In addition, we should give relevance to the results of the ECOG-ACRIN EA1141 study [97]. The effectiveness of standalone screening MRI for women with heterogeneously or extremely dense breasts was assessed by comparing abbreviated MRI to DBT, performed with randomised order of execution. Among 1444 women having either heterogeneously dense or extremely dense breasts, breast MRI successfully detected all 17 cases of invasive cancers and identified 5 out of 6 DCIS (83%). In contrast, DBT detected only 7 out of 17 invasive cancers (41%) and 2 out of 6 DCIS (33%). Sensitivity was significantly higher for MRI (96%) than for DBT (39%). Specificity was significantly higher for DBT (97%) than for MRI (87%). The additional imaging recommendation rate was significantly lower for MRI (8%) than for DBT (10%) while the positive predictive value of biopsy at lesion level was higher for DBT (36%) than for MRI (19%), without significant difference.
These study results clearly play in favour of abbreviated MRI screening protocols and show that DBT does not overcome the intrinsic limitations of mammography for screening women with dense breasts, even when a quasi-three-dimensional mammographic technique as DBT is applied. Furthermore, the perspective was enlarged to women with breast density ACR BI-RADS category c, considering that 77% of the women analysed had density c and only 15% had density d (8% had density b or even a, due to involution after the last screening mammogram). In fact, of the 16 BCs detected by MRI and undetected by DBT, 3 were in density d, 11 in density c, and 2 in density b. No interval cancers were observed during follow-up, but the intraindividual study design does not allow comparing the interval cancer rate for each of the two screening methods.
A recent systematic review and meta-analysis including 22 studies [99] reported that of 132,166 screened women with dense breasts and negative mammography, a total of 541 cancers missed at mammography were detected with supplemental modalities, including DBT, handheld or automated breast ultrasound, and MRI. MRI was significantly superior to the other modalities in cancer detection rate (1.52 per 1000 screenings), including invasive cancers (1.31 per 1000 screenings) and DCIS (1.91 per 1000 screenings), without significant differences in recall or biopsy rate. The authors highlight that the limited number of studies prevented assessment of interval cancer rates. Excluding MRI, no significant difference in any metrics was identified among the remaining modalities.
The integration of breast MRI for screening women with dense breasts into practice, despite its reported potential benefits (supported by comparative studies and finally substantiated by a RCT), has encountered several challenges. A prominent obstacle is the considerable cost associated with MRI screening, which includes not only the imaging itself but also the specialised equipment and personnel required [100]. A further practical problem is the request for more additional tests. These implications can place significant strains on healthcare systems, hampering their capacity to extend routine MRI screenings to a broader population beyond the subgroup of high-risk women. Presently, ultrasonography is a more common choice for supplemental screening thanks to its broader availability and lower implementation costs, despite its modest additional cancer detection rate, as also shown by the above-mentioned meta-analysis [99]. However, a risk-adjusted strategy could potentially optimise resource allocation [101, 102]: based on data from the DENSE trial, MRI alone every 4 years in women with extremely dense breasts is cost-effective with € 15,620 per quality-adjusted life years.
In this scenario, the most updated guidelines from the European Commission Initiative on Breast Cancer (ECIBC) [103] propose the following suggestions regarding asymptomatic women with high breast density 45−74 years old in the context of an organised population-based screening programme:
-
Not implement tailored MRI screening after a negative mammogram (issued in January 2020).
-
If high mammographic breast density is detected for the first time with digital mammography, implement tailored screening with DBT in the next screening round (issued in September 2021).
The update on MRI screening was undertaken a few months after the publication of the DENSE trial results and before the publication of the ECOG-ACRIN EA1141 study as well as of analyses and models about cost-effectiveness and possible prolonged intervals between MRIs. Of note, the ECIBC Guidelines Development Group defined this recommendation as “conditional” and with a “very low certainty of the evidence”. In addition, almost four years after issuing the guideline, the proposed research priorities (balance of effects, including the potential risk of adverse events due to contrast reaction; to improve the specificity of MRI-tailored screening; to study abbreviated protocols to make the intervention less costly and more acceptable) can be considered substantially solved. Nowadays, the recommendation in favour of DBT (which applies to women with both density c or d) appears taking into consideration more practical feasibility than the evidence available. It remains to see what the next ECIBC guidelines update will propose.
To summarise, despite level 1 evidence in favour of breast MRI screening of women with dense breasts, the practical challenges related to costs, availability, and additional assessments have prevented real adoption of this screening modality, even for the limited group of women with extremely dense breasts. An overall comparison between the two cases of breast MRI screening for women at high risk and for women with dense breasts is provided in Table 3.
Conclusion: a double difference between theory and practice
When comparing breast MRI screening in high-risk women and in women with extremely dense breasts, we appreciate a difference between the EBM theory and real-world practice. The difference in accuracy and BC detection in favour of MRI in high-risk women was so large that the new test was adopted regardless of the lack of results from RCTs. On the contrary, despite having positive results from an RCT, lack of resources does not allow implementation of breast MRI screening for women with extremely dense breasts. Women with extremely dense breasts are estimated to be on average 10% of the female population from 50 to 70 years of age [28], which can be translated into about 6−7 million in the European Union [104] (much more than those at high-risk, considering that for example, the prevalence of BRCA1 and BRCA2 mutation carriers in the general population is around 0.2% [105]). Health authorities in The Netherlands suggested an alternative way: contrast-enhanced mammography [106, 107] instead of MRI, due to its lower cost and higher accessibility [108]. Trials are ongoing, such as the C-MERIT [109] and the CMIST [110], but we need their results before adopting this solution.
The current era of big data is fostering a new way of thinking about the relation between RCTs and real-world evidence: a more fruitful interplay between them is expected [111, 112]. However, when we look at the gap between EBM theory and breast MRI screening, a sentence attributed to Manfred Eigen, 1967 Nobel Laureate in Chemistry, seems to be appropriate: “In theory, there is no difference between theory and practice. But in practice, there is”.
Notes
The ACS recommended breast MRI “as an adjunct to mammography”: (1) for women at familial/genetic high risk (BRCA-mutated women, their untested first-degree relatives, or with estimated lifetime risk ≥ 20–25%) on the basis of nonrandomized comparative studies, (2) for women who had radiation to chest between age 10 and 30 years on the only basis of estimated lifetime risk. The latter approach was used also for Li-Fraumeni syndrome and first-degree relatives as well as Cowden and Bannayan-Riley-Ruvalcaba syndromes and first-degree relatives. Of note, breast MRI screening recommendations on the only basis of lifetime risk estimates, without any supporting MRI study, were even more challenging the EBM theory than those based on test accuracy comparative studies.
Abbreviations
- ACR:
-
American College of Radiology
- ACS:
-
American Cancer Society
- BC:
-
Breast cancer
- BI-RADS:
-
Breast Imaging Reporting and Data System
- DBT:
-
Digital breast tomosynthesis
- DCIS:
-
Ductal carcinoma in situ
- EBM:
-
Evidence-based medicine
- MRI:
-
Magnetic resonance imaging
- NICE:
-
National Institute for Clinical Excellence
- NMR:
-
Nuclear magnetic resonance
- RCT:
-
Randomised controlled trial
References
Goldsmith M, Koutcher JA, Damadian R (1978) NMR in cancer, XIII: application of the NMR malignancy index to human mammary tumours. Br J Cancer 38:547–554. https://doi.org/10.1038/bjc.1978.243
Ross RJ, Thompson JS, Kim K, Bailey RA (1982) Nuclear magnetic resonance imaging and evaluation of human breast tissue: preliminary clinical trials. Radiology 143:195–205. https://doi.org/10.1148/radiology.143.1.7063727
el Yousef S, O’Connell D, Duchesneau R et al (1985) Benign and malignant breast disease: magnetic resonance and radiofrequency pulse sequences. AJR Am J Roentgenol 145:1–8. https://doi.org/10.2214/ajr.145.1.1
Heywang S, Fenzl G, Edmaier M et al (1985) Kernspintomographie in der Mammadiagnostik. Rofo 143:207–212. https://doi.org/10.1055/s-2008-1052791
Heywang SH, Hahn D, Schmidt H et al (1986) MR Imaging of the Breast Using Gadolinium-DTPA. J Comput Assist Tomogr 10:199–204. https://doi.org/10.1097/00004728-198603000-00005
Kaiser WA, Zeitler E (1989) MR imaging of the breast: fast imaging sequences with and without Gd-DTPA. Preliminary observations. Radiology 170:681–686. https://doi.org/10.1148/radiology.170.3.2916021
Sardanelli F, Podo F (2020) From NMR to Clinical Breast MRI. Breast MRI for High-risk Screening. Springer International Publishing, Cham, pp 1–9
Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1. Science (80- ) 266:66–71. https://doi.org/10.1126/science.7545954
Wooster R, Bignell G, Lancaster J et al (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792. https://doi.org/10.1038/378789a0
National Collaborating Centre for Primary Care (UK), National Collaborating Centre for Primary Care (2006) Familial breast cancer.The classification and care of women at risk of familial breast cancer in primary, secondary and tertiary care Update, July 2006 National Collaborating Centre for Primary Royal College of General Practitioners London
Saslow D, Boetes C, Burke W et al (2007) American cancer society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57:75–89. https://doi.org/10.3322/canjclin.57.2.75
Selamoglu A, Gilbert FJ (2020) Guidelines and Recommendations on High-Risk Breast Cancer Screening All Over the World: Agreements and Differences. Breast MRI for High-risk Screening. Springer International Publishing, Cham, pp 251–267
MRI for high risk women |Updated Medicare information for funding of MRI scans for women under 50 at high risk of breast cancer. https://www.canceraustralia.gov.au/clinical-best-practice/breast-cancer/screening-and-early-detection/mri-high-risk-women. Accessed 18 Nov 2023
Daly MB, Pal T, Berry MP et al (2021) Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 19:77–102. https://doi.org/10.6004/jnccn.2021.0001
Singer CF, Tea MK, Pristauz G et al (2015) Clinical Practice Guideline for the prevention and early detection of breast and ovarian cancer in women from HBOC (hereditary breast and ovarian cancer) families. Wien Klin Wochenschr 127:981–986. https://doi.org/10.1007/s00508-015-0880-x
Bick U, Engel C, Krug B et al (2019) High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer. Breast Cancer Res Treat 175:217–228. https://doi.org/10.1007/s10549-019-05152-9
Biganzoli L, Calabrese M, Conte B, et al (2018) AIOM Breast neoplasms guidelines. Available via https://www.aiom.it/linee-guida-aiom-2018-neoplasie-della-mammella-11/
Llort G, Chirivella I, Morales R et al (2015) SEOM clinical guidelines in hereditary breast and ovarian cancer. Clin Transl Oncol 17:956–961. https://doi.org/10.1007/s12094-015-1435-3
The Israel Cancer Association – Breast Cancer. https://en.cancer.org.il/template_e/default.aspx?PageId=7749
Bart G, Frans G, Guido VH, et al (2016) Richtlijnen – BORSTKANKERSCREENING. Antwerpen
Ontario Breast Screening Program Screening for Women at High Risk – Cancer Care Ontario. https://www.cancercareontario.ca/en/guidelinesadvice/cancer-continuum/screening/breast-cancer-high-risk
Tjelle TE, Einar T, Movik E et al (2018) Diagnostic accuracy, clinical effectiveness and budget impact of screening BRCA1/2 mutation carriers by MRI. A health technology assessment, Oslo. Available via https://www.fhi.no/en/publ/2018/Diagnostic-accuracy-clinical-effectiveness-and-budget-impact-of-screening-BRCA1-2-mutation-carriers-by-MRI/
Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. London: National Institute for Health and Care Excellence (NICE) https://pubmed.ncbi.nlm.nih.gov/31940157/
Jaeschke R (1994) Users’ guides to the medical literature. III. How to use an article about a diagnostic test. B. what are the results and will they help me in caring for my patients? the evidence-based medicine working group. JAMA 271:703–707. https://doi.org/10.1001/jama.271.9.703
Irwig L, Houssami N, Armstrong B, Glasziou P (2006) Evaluating new screening tests for breast cancer. BMJ 332:678–679. https://doi.org/10.1136/bmj.332.7543.678
Zackrisson S, Andersson I, Janzon L et al (2006) Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study. BMJ 332:689–692. https://doi.org/10.1136/bmj.38764.572569.7C
Bakker MF, de Lange SV, Pijnappel RM et al (2019) Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med 381:2091–2102. https://doi.org/10.1056/NEJMoa1903986
D’Orsi CJ, Sickles EA, Mendelson EB, Morris EA (2013) ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System, 5th edn. American College of Radiology, Reston, VA, USA
Mann RM, Athanasiou A, Baltzer PAT et al (2022) Breast cancer screening in women with extremely dense breasts recommendations of the European Society of Breast Imaging (EUSOBI). Eur Radiol 32:4036–4045. https://doi.org/10.1007/s00330-022-08617-6
Raat HPJ, Lobbes MBI, Veldhuis WB (2021) [Are The Netherlands ready for personalized breast cancer screening? Abbreviated breast MRI and contrast-enhanced mammography for screening in women with dense breasts]. Ned Tijdschr Geneeskd 165.
Gray JAM (1998) The first report of the national screening committee. J Med Screen 5:169–169. https://doi.org/10.1136/jms.5.4.169
World Health Organization, Regional Office for Europe (2020) Screening programmes: a short guide. Increase effectiveness, maximize benefits and minimize harm. Available via https://iris.who.int/handle/10665/330829
Gilbert R (2001) Assessing diagnostic and screening tests: Part 1 Concepts. West J Med 174:405–409. https://doi.org/10.1136/ewjm.174.6.405
Dickinson JA, Pimlott N, Grad R et al (2018) Screening: when things go wrong. Can Fam Physician 64:502–508
Rasmussen JF, Siersma V, Malmqvist J, Brodersen J (2020) Psychosocial consequences of false positives in the Danish Lung Cancer CT screening trial: a nested matched cohort study. BMJ Open 10:e034682. https://doi.org/10.1136/bmjopen-2019-034682
Brodersen J, Siersma VD (2013) Long-term psychosocial consequences of false-positive screening mammography. Ann Fam Med 11:106–115. https://doi.org/10.1370/afm.1466
Lafata JE, Simpkins J, Lamerato L et al (2004) The economic impact of false-positive cancer screens. Cancer Epidemiol Biomarkers Prev 13:2126–32. https://doi.org/10.1158/1055-9965.2126.13.12
Welch HG, Black WC (2010) Overdiagnosis in cancer. J Natl Cancer Inst 102:605–613. https://doi.org/10.1093/jnci/djq099
Sardanelli F, Trimboli RM, Tot T (2018) Expert review of breast pathology in borderline lesions. JAMA Oncol 4:1325–26. https://doi.org/10.1001/jamaoncol.2018.1953
Jenniskens K, de Groot JAH, Reitsma JB et al (2017) Overdiagnosis across medical disciplines: a scoping review. BMJ Open 7:e018448. https://doi.org/10.1136/bmjopen-2017-018448
McCaffery KJ, Jacklyn GL, Barratt A et al (2015) Recommendations About Screening. In: Guyatt G, Rennie D, Meade MO, Cook DJ (eds) Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3rd edn. McGraw-Hill Education, New York, NY
Council of the European Union (2022) Council Recommendation on strengthening prevention through early detection: A new EU approach on cancer screening replacing Council Recommendation 2003/878/EC. https://data.consilium.europa.eu/doc/document/ST-14770-2022-INIT/en/pdf
Carter JL, Coletti RJ, Harris RP (2015) Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods. BMJ 350:g7773–g7773. https://doi.org/10.1136/bmj.g7773
Lawrence G, Wallis M, Allgood P et al (2009) Population estimates of survival in women with screen-detected and symptomatic breast cancer taking account of lead time and length bias. Breast Cancer Res Treat 116:179–185. https://doi.org/10.1007/s10549-008-0100-8
Mahnken JD, Chan W, Freeman DH, Freeman JL (2008) Reducing the effects of lead-time bias, length bias and over-detection in evaluating screening mammography: a censored bivariate data approach. Stat Methods Med Res 17:643–663. https://doi.org/10.1177/0962280207087309
Spix C, Michaelis J, Berthold F et al (2003) Lead-time and overdiagnosis estimation in neuroblastoma screening. Stat Med 22:2877–2892. https://doi.org/10.1002/sim.1533
Biesheuvel C, Barratt A, Howard K et al (2007) Effects of study methods and biases on estimates of invasive breast cancer overdetection with mammography screening: a systematic review. Lancet Oncol 8:1129–1138. https://doi.org/10.1016/S1470-2045(07)70380-7
Sardanelli F, Di Leo G (2009) Bias in Studies on Diagnostic Performance. In: Biostatistics for Radiologists. Springer Milan, Milano, pp 165–179
Trimboli RM, Giorgi Rossi P, Battisti NML et al (2020) Do we still need breast cancer screening in the era of targeted therapies and precision medicine? Insights Imaging 11:105. https://doi.org/10.1186/s13244-020-00905-3
Perry N, Broeders M, de Wolf C et al (2008) European guidelines for quality assurance in breast cancer screening and diagnosis. Fourth edition—summary document. Ann Oncol 19:614–622. https://doi.org/10.1093/annonc/mdm481
Sardanelli F, Fallenberg EM, Clauser P et al (2017) Mammography: an update of the EUSOBI recommendations on information for women. Insights Imaging 8:11–18. https://doi.org/10.1007/s13244-016-0531-4
Sardanelli F, Aase HS, Álvarez M et al (2017) Position paper on screening for breast cancer by the European Society of Breast Imaging (EUSOBI) and 30 national breast radiology bodies from Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, G. Eur Radiol 27:2737–2743. https://doi.org/10.1007/s00330-016-4612-z
Schünemann HJ, Lerda D, Quinn C et al (2020) Breast cancer screening and diagnosis: a synopsis of the European breast guidelines. Ann Intern Med 172:46. https://doi.org/10.7326/M19-2125
Schünemann HJ, Lerda D, Dimitrova N et al (2019) Methods for development of the European commission initiative on breast cancer guidelines. Ann Intern Med 171:273. https://doi.org/10.7326/M18-3445
European Commission Initiative on Breast Cancer (2019) European Commission Initiative on Breast Cancer (ECIBC): European guidelines on breast cancer screening and diagnosis. http://healthcare-quality.jrc.ec.europa.eu
Lauby-Secretan B, Scoccianti C, Loomis D et al (2015) Breast-cancer screening — viewpoint of the IARC working group. N Engl J Med 372:2353–2358. https://doi.org/10.1056/NEJMsr1504363
Sardanelli F (2015) Screening mammography: a clear statement by the IARC Handbook. Epidemiol Prev 3:149–150
Kuhl CK, Schmutzler RK, Leutner CC et al (2000) Breast MR imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results. Radiology 215:267–279. https://doi.org/10.1148/radiology.215.1.r00ap01267
Kuhl CK, Schrading S, Leutner CC et al (2005) Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23:8469–8476. https://doi.org/10.1200/JCO.2004.00.4960
Podo F, Sardanelli F, Canese R et al (2002) The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk. J Exp Clin Cancer Res 21:115–24
Sardanelli F, Podo F, D’Agnolo G et al (2007) Multicenter Comparative Multimodality Surveillance of Women at Genetic-Familial High Risk for Breast Cancer (HIBCRIT Study): Interim Results. Radiology 242:698–715. https://doi.org/10.1148/radiol.2423051965
Sardanelli F, Podo F, Santoro F et al (2011) Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the High Breast Cancer Risk Italian 1 Study). Invest Radiol 46:94–105. https://doi.org/10.1097/RLI.0b013e3181f3fcdf
Kriege M, Brekelmans CTM, Boetes C et al (2004) Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351:427–437. https://doi.org/10.1056/NEJMoa031759
Rijnsburger AJ, Obdeijn I-M, Kaas R et al (2010) BRCA1 -Associated breast cancers present differently from brca2 -associated and familial cases: long-term follow-up of the dutch MRISC screening study. J Clin Oncol 28:5265–5273. https://doi.org/10.1200/JCO.2009.27.2294
Warner E, Plewes DB, Hill KA et al (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292:1317–25. https://doi.org/10.1001/jama.292.11.1317
Leach MO, Boggis CRM, Dixon AK et al (2005) Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 365:1769–1778. https://doi.org/10.1016/S0140-6736(05)66481-1
Lehman CD, Blume JD, Weatherall P et al (2005) Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 103:1898–1905. https://doi.org/10.1002/cncr.20971
Hagen AI, Kvistad KA, Maehle L et al (2007) Sensitivity of MRI versus conventional screening in the diagnosis of BRCA-associated breast cancer in a national prospective series. Breast 16:367–374. https://doi.org/10.1016/j.breast.2007.01.006
Riedl CC, Ponhold L, Flöry D et al (2007) Magnetic resonance imaging of the breast improves detection of invasive cancer, preinvasive cancer, and premalignant lesions during surveillance of women at high risk for breast cancer. Clin Cancer Res 13:6144–6152. https://doi.org/10.1158/1078-0432.CCR-07-1270
Riedl CC, Luft N, Bernhart C et al (2015) Triple-Modality screening trial for familial breast cancer underlines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density. J Clin Oncol 33:1128–1135. https://doi.org/10.1200/JCO.2014.56.8626
Kuhl C, Weigel S, Schrading S et al (2010) Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: The EVA Trial. J Clin Oncol 28:1450–1457. https://doi.org/10.1200/JCO.2009.23.0839
Trop I, Lalonde L, Mayrand MH et al (2010) Multimodality breast cancer screening in women with a familial or genetic predisposition. Curr Oncol 17:28–36. https://doi.org/10.3747/co.v17i3.494
Mann RM, Kuhl CK, Kinkel K, Boetes C (2008) Breast MRI: guidelines from the European Society of Breast Imaging. Eur Radiol 18:1307–1318. https://doi.org/10.1007/s00330-008-0863-7
Mann RM, Balleyguier C, Baltzer PA et al (2015) Breast MRI: EUSOBI recommendations for women’s information. Eur Radiol 25:3669–3678. https://doi.org/10.1007/s00330-015-3807-z
Sardanelli F, Boetes C, Borisch B et al (2010) Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur J Cancer 46:1296–1316. https://doi.org/10.1016/j.ejca.2010.02.015
Monticciolo DL, Newell MS, Moy L et al (2018) Breast cancer screening in women at higher-than-average risk: recommendations from the ACR. J Am Coll Radiol 15:408–414. https://doi.org/10.1016/j.jacr.2017.11.034
Monticciolo DL, Newell MS, Moy L et al (2023) Breast cancer screening for women at higher-than-average risk: updated recommendations from the ACR. J Am Coll Radiol 20:902–914. https://doi.org/10.1016/j.jacr.2023.04.002
Baltzer PAT, Sardanelli F (2020) The Mantra about Low Specificity of Breast MRI. Breast MRI for High-risk Screening. Springer International Publishing, Cham, pp 11–21
Sardanelli F, Di Leo G, Houssami N (2020) Systematic Reviews, Meta-Analyses, and Cost-Effective Analyses on Breast MRI Screening of High-Risk Women. Breast MRI for High-risk Screening. Springer International Publishing, Cham, pp 167–187
Sardanelli F, Podo F (2020) Primary Studies on Breast MRI Screening of High-Risk Women. Breast MRI for High-risk Screening. Springer International Publishing, Cham, pp 131–151
Goldstein CE, Weijer C, Brehaut JC et al (2018) Ethical issues in pragmatic randomized controlled trials: a review of the recent literature identifies gaps in ethical argumentation. BMC Med Ethics 19:14. https://doi.org/10.1186/s12910-018-0253-x
Saadatmand S, Geuzinge HA, Rutgers EJT et al (2019) MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): a multicentre, randomised, controlled trial. Lancet Oncol 20:1136–1147. https://doi.org/10.1016/S1470-2045(19)30275-X
Tilanus-Linthorst MMA, Kriege M, Boetes C et al (2005) Hereditary breast cancer growth rates and its impact on screening policy. Eur J Cancer 41:1610–1617. https://doi.org/10.1016/j.ejca.2005.02.034
Chen H, Wu J, Zhang Z et al (2018) Association between BRCA status and triple-negative breast cancer: a meta-analysis. Front Pharmacol 9:909. https://doi.org/10.3389/fphar.2018.00909
Podo F, Santoro F, Di Leo G et al (2016) Triple-negative versus non–triple-negative breast cancers in high-risk women: phenotype features and survival from the HIBCRIT-1 MRI-Including Screening Study. Clin Cancer Res 22:895–904. https://doi.org/10.1158/1078-0432.CCR-15-0459
Heywang-Köbrunner SH, Hacker A (2020) Breast MRI Screening for the Intermediate Risk: An Open Issue. Breast MRI for High-risk Screening. Springer International Publishing, Cham, pp 343–354
Nazari SS, Mukherjee P (2018) An overview of mammographic density and its association with breast cancer. Breast Cancer 25:259–267. https://doi.org/10.1007/s12282-018-0857-5
McCormack VA (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15:1159–1169. https://doi.org/10.1158/1055-9965.EPI-06-0034
Freer PE (2015) Mammographic breast density: impact on breast cancer risk and implications for screening. Radiographics 35:302–315. https://doi.org/10.1148/rg.352140106
Skaane P, Bandos AI, Gullien R et al (2013) Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology 267:47–56. https://doi.org/10.1148/radiol.12121373
Conant EF, Barlow WE, Herschorn SD et al (2019) Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol 5:635–642. https://doi.org/10.1001/jamaoncol.2018.7078
Li T, Houssami N, Noguchi N et al (2022) Differential detection by breast density for digital breast tomosynthesis versus digital mammography population screening: a systematic review and meta-analysis. Br J Cancer 127:116–125. https://doi.org/10.1038/s41416-022-01790-x
Houssami N, Hofvind S, Soerensen AL et al (2021) Interval breast cancer rates for digital breast tomosynthesis versus digital mammography population screening: an individual participant data meta-analysis. EClinicalMedicine 34:100804. https://doi.org/10.1016/j.eclinm.2021.100804
Magni V, Cozzi A, Schiaffino S et al (2023) Artificial intelligence for digital breast tomosynthesis: Impact on diagnostic performance, reading times, and workload in the era of personalized screening. Eur J Radiol 158:110631. https://doi.org/10.1016/j.ejrad.2022.110631
Emaus MJ, Bakker MF, Peeters PHM et al (2015) MR Imaging as an additional screening modality for the detection of breast cancer in women aged 50–75 years with extremely dense breasts: The DENSE trial study design. Radiology 277:527–537. https://doi.org/10.1148/radiol.2015141827
Veenhuizen SGA, de Lange SV, Bakker MF et al (2021) Supplemental breast MRI for women with extremely dense breasts: results of the second screening round of the DENSE trial. Radiology 299:278–286. https://doi.org/10.1148/radiol.2021203633
Comstock CE, Gatsonis C, Newstead GM et al (2020) Comparison of abbreviated breast MRI vs digital breast tomosynthesis for breast cancer detection among women with dense breasts undergoing screening. JAMA 323:746. https://doi.org/10.1001/jama.2020.0572
den Dekker BM, Bakker MF, de Lange SV et al (2021) Reducing False-positive screening mri rate in women with extremely dense breasts using prediction models based on data from the DENSE trial. Radiology 301:283–292. https://doi.org/10.1148/radiol.2021210325
Hussein H, Abbas E, Keshavarzi S et al (2023) Supplemental breast cancer screening in women with dense breasts and negative mammography: a systematic review and meta-analysis. Radiology 306(3)
Mann RM, Cho N, Moy L (2019) Breast MRI: State of the Art. Radiology 292:520–536. https://doi.org/10.1148/radiol.2019182947
Geuzinge HA, Bakker MF, Heijnsdijk EAM et al (2021) Cost-effectiveness of magnetic resonance imaging screening for women with extremely dense breast tissue. J Natl Cancer Inst 113:1476–1483. https://doi.org/10.1093/jnci/djab119
Kuhl CK, Baltzer P (2021) You Get what you pay for: breast MRI screening of women with dense breasts is cost-effective. J Natl Cancer Inst 113:1439–1441. https://doi.org/10.1093/jnci/djab120
European Commission Initiative on Breast Cancer (2020) European guidelines on breast cancer screening and diagnosis. https://healthcare-quality.jrc.ec.europa.eu/en/ecibc/european-breast-cancer-guidelines?topic=61&usertype=60&filter_1=106&filter_2=108&updatef2=0
Monika K (2021) Demographic Outlook for the European Union
Janavičius R (2010) Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. EPMA J 1:397–412. https://doi.org/10.1007/s13167-010-0037-y
Cozzi A, Schiaffino S, Sardanelli F (2019) The emerging role of contrast-enhanced mammography. Quant Imaging Med Surg 9:2012–2018. https://doi.org/10.21037/qims.2019.11.09
Cozzi A, Magni V, Zanardo M et al (2022) Contrast-enhanced mammography: a systematic review and meta-analysis of diagnostic performance. Radiology 302:568–581. https://doi.org/10.1148/radiol.211412
Health Council of the Netherlands (2020) The use of MRI screening in the population screening programme for breast cancer
The C-MERIT Screening Cohort: Contrast-enhanced Mammography for Breast Cancer Screening and Risk Assessment in Women With Dense Breasts. https://www.clinicaltrials.gov/study/NCT05667532
Comparison of Breast Cancer Screening With CESM to DBT in Women With Dense Breasts (CMIST). https://www.clinicaltrials.gov/study/NCT05625659
Colarieti A, Sardanelli F (2023) Clinical trials for evidence-based radiology: to randomize or not to randomize? This is the question. Radiol Med. https://doi.org/10.1007/s11547-023-01746-y
Sheldrick RC (2023) Randomized trials vs real-world evidence. JAMA 329:1352. https://doi.org/10.1001/jama.2023.4855
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Fiona J. Gilbert is supported by the NIHR Cambridge biomedical research centre.
This article belongs to the thematic series entitled “Translating radiological research into practice – from discovery to clinical impact”.
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Francesco Sardanelli participated in conceptualisation, design, drafting, and editing of the paper. Veronica Magni participated in the conceptualisation, drafting, and editing of the paper. Gabriele Rossini participated in drafting and editing of the paper. Fleur Kilburn-Toppin participated in drafting and editing of the paper. Nuala A. Healy participated in drafting and editing of the paper. Fiona J. Gilbert oversaw and participated in the conceptualisation, design, drafting, and editing of the paper. All authors saw and approved the final version, and no other person made a substantial contribution to the paper.
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Sardanelli, F., Magni, V., Rossini, G. et al. The paradox of MRI for breast cancer screening: high-risk and dense breasts—available evidence and current practice. Insights Imaging 15, 96 (2024). https://doi.org/10.1186/s13244-024-01653-4
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DOI: https://doi.org/10.1186/s13244-024-01653-4