Biomarkers Breast
The following list has been reviewed and approved by the European Society of Breast Imaging (EUSOBI)
|
Biomarker |
Target |
Level of evidence |
Evidence |
Acquisition requirements |
Reading |
Issues |
Established biomarkers |
Mammographic breast density |
Breast cancer risk, stratification of mammographic sensitivity |
1 [1-4!] |
Substantial |
Mammography |
Qualitative ACR BI-RADS, quantitative computer-assisted (commercial) |
Standardization, reproducibility of visual assessment, Individual CAD systems reproducible but poor inter reproducibility. |
|
ADC |
Differential diagnosis of breast MRI lesions, response to NAC |
1 [5-13!] |
Substantial |
MRI with DWI, 2 b-values 0-50 and 800 s/mm2 |
Visual co-registration of enhancing lesion and ADC map, ROI |
Standardization, generally accepted cut-off, pitfalls |
|
Pharmacokinetic mapping of DCE data in breast MRI |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
2-3 [14-18!] |
Limited (due to heterogeneity) |
MRI T1w DCE sequence, temporal resolution <20 sec |
Multiple available models, most common free deconvolution, Tofts, modified Tofts |
Huge standardization issues |
|
Ultrafast DCE-MRI markers |
Differential diagnosis of breast MRI lesions |
2 [19-23!] |
Moderate |
MRI T1w DCE acquisition with a temporal resolution around 5 sec |
Time-to-Enhancement (TTE)/time-of-arrival (TOA), maximum slope, initial slope, initial enhancement ratio, initial area under the curve |
Standardization, generally accepted cut-off |
|
Kaiser score |
Differential diagnosis of breast MRI lesions |
1 [24-29!] |
Moderate |
Breast MRI according to international recommendations |
Visual assessment of 5 dynamic and morphologic features |
Official accreditation by societies |
|
Shear Wave Velocity/ Strain elasticity |
Differential diagnosis, evaluation of treatment response |
1-2 [30-34!] |
Moderate |
US device with elastography capability |
Visual assessment, ROI for quantitative measurements, ratios |
Standardization, generally accepted cut-offs |
|
Doppler ultrasound: RI/PI |
Differential diagnosis, evaluation of treatment response |
2 [35, 36!] |
Limited |
Doppler ultrasound |
Acquisition of blood flow spectrum |
Standardization, generally accepted cut-offs |
|
Contrast-enhanced ultrasound general |
Differential diagnosis, evaluation of treatment response |
2 [37!] |
Moderate |
Contrast enhanced ultrasound |
Visual assessment, ROI for time-signal intensity curves |
Standardization, generally accepted criteria |
|
CEUS parameters Time to peak, peak intensity, wash-in & wash-out rate, area under curve |
Differential diagnosis, evaluation of treatment response |
2-3 [36, 37!] |
Limited |
Contrast enhanced ultrasound |
Visual assessment, ROI for time-signal intensity curves |
Standardization, identification of most useful quantitative parameters, generally accepted cut-offs |
Biomarkers under investigation /in development |
Advanced Diffusion Weighted Imaging |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
2-3 [12!, 38-53!] |
Moderate |
MRI, acquisition parameters depend on specific technique |
Data analysis depends on specific technique |
Standardization, accepted cut-offs |
|
Volumetric automated assessment of DCE data in breast MRI |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
2 [16!, 54-63!] |
Moderate |
MRI T1w DCE sequence |
Multiple software tools available, detection of hotspot/most suspicious enhancement, volume of enhancement, distribution of curve-types within lesion |
Definite use-case, standardization |
|
Background parenchymal enhancement (breast MRI) |
Breast cancer risk, prediction of response to NAT |
1 [64-73!] |
Moderate |
Dynamic-Contrast-Enhanced MRI |
Qualitative ACR BI-RADS, quantitative (experimental) |
Standardization, conflicting evidence |
|
Total Choline (tCho) from proton MR-spectroscopy |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
1 [74-78!] |
Moderate |
MR-spectroscopy sequence, PRESS or STEAM, TE30-270ms, best 135 ms |
Postprocessing, then visual assessment, SNR determination or quantitation |
Standardization, low technical sensitivity |
|
FDG-uptake (PET) |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
2 [36!, 79-86!] |
Moderate |
18F-labeled Fluor-deoxyglucose PET |
Visual, ROI for SUV evaluation |
Standardization, clinical use-case |
|
FEC-uptake (PET) |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
3 [87-89!] |
Limited |
18F-labeled Fluor-ethylcholine PET |
Visual, ROI for SUV evaluation |
Standardization, clinical use-case |
|
FES-uptake (PET) |
Whole body staging and response to therapy |
3-4 [90-95!] |
Limited |
16α-[18F]-fluoro-17β-estradiol PET |
Visual, ROI for SUV evaluation |
Standardization, clinical use-case |
|
FDG Background parenchymal uptake (PET) |
Breast cancer risk, cancer phenotyping, response assessment to NAT |
3 [86!, 96-98!] |
Limited |
18F-labeled Fluor-deoxyglucose PET |
ROI/VOI for SUV evaluation |
Standardization, conflicting evidence |
|
Radiomics and Radiogenomics signatures, Deep learning, A.I. |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
2-3 [99-102!] |
Limited |
Imaging data |
|
|
|
Oxygenated/ Deoxygenated Haemoglobin |
Differential diagnosis (benign vs malignant), response assessment to NAT |
3 |
Limited |
Optical imaging |
MIPs, parametric maps, visual assessment, quantification of concentration |
Standardisation, clinical use |
|
Quantitative ultrasound parameters (attenuation/ scatter coefficients, entropy, textural parameters etc.) |
Differential diagnosis (benign vs malignant), response assessment to NAT |
3 |
Limited |
Quantitative ultrasound techniques |
Data analysis depends on specific technique |
Standardization, clinical use |
|
Peritumoral oedema |
Differential diagnosis (benign vs malignant), cancer phenotyping, response assessment to NAT |
2 [103-109!] |
moderate |
MRI T2w sequence
|
Qualitative, Visual assessment |
Standardization, reproducibility of visual assessment, clinical use |
|
CESM |
Differential diagnosis (benign vs malignant), response assessment to NAT |
2-3 [110-113!] |
Limited |
Contrast-enhanced mammography |
Visual assessment of enhancement; semiquantitative contrast measures under investigation |
Needs representative data & benchmarking against standard of care |
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- Di Giovanni P, Azlan CA, Ahearn TS, et al (2010) The accuracy of pharmacokinetic parameter measurement in DCE-MRI of the breast at 3 T. Phys Med Biol 55:121–132. https://doi.org/10.1088/0031-9155/55/1/008
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- Pineda FD, Medved M, Wang S, et al (2016) Ultrafast Bilateral DCE-MRI of the Breast with Conventional Fourier Sampling: Preliminary Evaluation of Semi-quantitative Analysis. Acad Radiol 23:1137–1144. https://doi.org/10.1016/j.acra.2016.04.008
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- Wengert GJ, Pipan F, Almohanna J, et al (2020) Impact of the Kaiser score on clinical decision-making in BI-RADS 4 mammographic calcifications examined with breast MRI. Eur Radiol 30:1451–1459. https://doi.org/10.1007/s00330-019-06444-w
- Milos RI, Pipan F, Kalovidouri A, et al (2020) The Kaiser score reliably excludes malignancy in benign contrast-enhancing lesions classified as BI-RADS 4 on breast MRI high-risk screening exams. Eur Radiol 30:6052–6061. https://doi.org/10.1007/s00330-020-06945-z
- Baltzer PAT, Dietzel M, Kaiser WA (2013) A simple and robust classification tree for differentiation between benign and malignant lesions in MR-mammography. Eur Radiol 23:2051–2060. https://doi.org/10.1007/s00330-013-2804-3
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- Huang R, Jiang L, Xu Y, et al (2019) Comparative Diagnostic Accuracy of Contrast-Enhanced Ultrasound and Shear Wave Elastography in Differentiating Benign and Malignant Lesions: A Network Meta-Analysis. Front Oncol 9:102. https://doi.org/10.3389/fonc.2019.00102
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