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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