Mammography is mandatory for symptoms or complaints developing in patients aged over 30–35 years. In justified cases, it can be carried out in patients aged under 30. Mammography is the only scientifically proven method for screening asymptomatic women at average risk with the purpose of reducing breast cancer mortality (2). Direct digital mammography has been shown to perform better than conventional analogue techniques (3). As the screening age for mammography varies from country to country, the age cut-off for mammography and US scans should be adjusted accordingly.

Digital breast tomosynthesis (DBT) is a procedure based on full-field digital mammography (FFDM) in which an X-ray tube moving in an arc capturing 10–15 overlapping digital images of the breast in a short time at low radiation doses. Data are computer- processed, resulting in thin slice images and can be reconstructed to summation images called “synthetic 2D images,” which look similar to conventional images. In order to reduce radiation dose, it is recommended that conventional 2D images be partially or completely replaced with synthetic 2D images, provided that the device has an official certificate (e.g., FDA approval). 3D tomosynthesis is more sensitive for the assessment of breast structure, and hidden lesions are easier to be detected (higher sensitivity). Tomosynthesis is highly efficient (higher specificity) in assessing overlapping tissues (summation) that pose diagnostic difficulties during conventional 2D imaging. By analysing images cut into thin slices, breast structure can be assessed without the disturbing effects of overlapping, so that pathological structural distortions and lesion borders can be evaluated more accurately, and false-positive results resulting from summation can be eliminated. As a result, 29%–41% more tumours can be detected and, if applied during screening, recall rates are significantly reduced, and unnecessary biopsies can be avoided. Use of tomosynthesis in breast screening is particularly advantageous for breast structures (dense fibrotic, fibroadenotic tissue) for which conventional mammography has a lower sensitivity (4, 5).

One of the latest developments in digital mammography is the use of intravenous iodinated contrast media for dual-energy mammography. The subtraction technique allows for analysis of contrast accumulation in breast lesions, similarly to breast MRI. According to some studies, CESM may be suitable for the assessment of abnormalities detected by mammography, especially for dense breast structures, to evaluate the extent of the disease. According to some reports, its sensitivity is close to that of a breast MRI, but this has not yet been clearly established for DCIS. Radiation exposure is 81% higher than for a conventional 2D digital mammography, and 48% higher than for DBT (6–8). Currently, this modality is being researched and may only be used with serious reservations, and it must never be a substitute for indications that have long been supported by evidence (e.g., mammography, breast MRI) (9, 10).

Breast ultrasound can be used on its own in patients aged under 30. Over the age of 30–35 years, it can be a complementary procedure to mammography, when needed (11). It is not suitable for breast cancer screening, at any age. As for ultrasound scans of other regions, breast ultrasound scanning should be documented with images in accordance with professional rules, even in negative cases. Colour Doppler is optional, but can be used in addition. Some studies suggest that a significant number of malignancies can be detected by ultrasound scanning as a complement for mammography (12), but this has not yet been routinely introduced due to extra human resource requirements and a high false positive rate.

Automated breast ultrasound scan hasn’t become widespread yet as a complementary investigation modality for dense breast structures (13, 14). Using a probe covering the breast, volumetric data are collected about the entire breast, from which slices can be reconstructed to review the glandular tissue in the main anatomical planes. This modality provides a good anatomical overview, as it is reproducible, and it can be complemented by an automatic image recognition system. Its disadvantage is that the false positivity rate is high for the biopsies it indicates, most of which will be benign (15). It should be emphasized that the resolution and information content of ultrasound images provided by ABUS is the same as for manual ultrasound scanning.

In most states of the United States, for high density breasts, it is mandatory to inform patients about investigations that complement screening mammography (e.g., ultrasound). Mammographic breast density, as an independent risk factor, is still subject to scientific debate; however, the tumour-masking effect of a higher density, which makes tumour detection difficult, is an accepted fact (16).

This is a combination of digital breast tomosynthesis and automated breast ultrasound. This modality is part of a research project, and it is not yet commercially available. This device captures tomosynthetic mammography images in a conventional CC and MLO setup, after which 3D ultrasound images are recorded by an automatic ultrasound device built into the compression plate. Studies have shown that the combination of ultrasound scanning and mammography in screening may significantly improve the rate of detected abnormalities. This method utilizes the advantages of both tomosynthesis and automated ultrasound scanning over the 2D technique (17, 18).

If an MRI image suggests malignancy, targeted (second look) ultrasound scanning is recommended even if the lesion was hidden on mammography and on the first ultrasound scan. It is important that this is done by a radiologist experienced in breast MRI. By doing this, 60%70% of originally occult lesions can be detected, and ultrasound-guided sampling can be performed (19).

Shearwave sonoelastography is a non-invasive imaging procedure based on tissue elasticity, measured in kPA. An abnormal process will modify the elastic properties of the affected tissue (20). According to studies, ultrasound elastography may help differentiate BI-RADS 3 and 4a lesions, and may increase the specificity of ultrasound scanning, thereby reducing the number of unnecessary breast biopsies (21, 22). The role of elastography in the monitoring of neoadjuvant treatments, in the differential diagnosis of suspected axillary lymph nodes, and in the evaluation of microcalcifications affecting the glandular tissue has been investigated. This method has also been integrated into the current BI-RADS lexicon of 2013 (23).

Ductography may be used when an intraductal process is clinically suspected if this cannot be excluded by other imaging and intervention methods. It can also be used for dye marking of affected ducts before surgery. Because of its low sensitivity and specificity, it is not suitable for excluding an intraductal process in the event of a negative result. In some countries (e.g., the United Kingdom) it has been removed from the list of interventions used in practice. MRI has started to take over the role of ductography. Based on a large review study, the sensitivity and specificity of MRI (92% and 97%, respectively) for carcinomas are significantly higher than for galactography in the diagnosis of patients with discharging breasts. In the event of negative mammography and ultrasound results, MRI scanning is recommended as a next step of assessment (28).

• Not suitable for breast screening (29–38).

Positron emission mammography alone is not suitable for breast screening. PEM is a dedicated breast camera with a resolution of 1–2 mm that can be used as a complementary method to mammography and breast ultrasound. It is primarily recommended in patients in whom MRI scanning is not indicated or not feasible for any reason. Its sensitivity and specificity in the identification of malignant foci within the breast are nearly identical to those of MRI. It can be used to determine multiplicity within the breast, to differentiate scar and tumour in an operated breast, and to measure response to chemotherapy. Stereotactic sampling systems used in mammography can also be used for PEM (device dependent). When using the method, radiation exposure (3.0–3.5 mSv) to the radiopharmaceutical used (which is not focused to the breast) should be taken into account (39). Not available in Hungary.

PET/MRI is a promising technique that is still primarily used for research; its use is recommended in patients for whom PET and MRI indications coexist and minimization of radiation exposure is essential (40, 41).

Sampling should always be guided by an imaging technique, for both palpable and non-palpable lesions.

• Ultrasound-guided sampling of the breast and regional lymph nodes is recommended if the palpable or non-palpable lesion is clearly visible on ultrasound.

It is strongly contraindicated that after an ultrasound-guided sampling with a benign result. Lesions which are not well identifiable by ultrasound are followed-up only.

• Mammography-guided (stereotactic) sampling is required for non-palpable, non-ultrasound-identifiable lesions that are not certainly benign, e.g., microcalcifications. Aiming can be done in a sitting/lying/or side lying position. Lesions visible only on tomosynthesis (mostly structural distortions) may only be aimed at by tomosynthetic stereotaxis (which cannot be replaced by MRI). The latter method is not currently funded by the NEAK (National Health Insurance Fund of Hungary).

Fine needle aspiration cytology (FNA, FNAB, FNAC), core biopsy, and VAB are all extremely important in diagnosis and therapeutic planning. Cytology is a faster, cheaper, but more inaccurate procedure (more false negatives and non-evaluable specimens), while core biopsy is more accurate (histological type, immunohistochemical parameters, definitive confirmation of benignity), and usually eliminates errors in evaluating fibrotic lesions and lesions in treated breasts. Because of the low reliability of FNA, it is contraindicated in some countries for breast diagnostics—except for evaluation of fluid-containing structures.

In some cases, VAB is the first choice of method according to current recommendations.

Detailed, state-of-the-art professional recommendations and possibly local availability should be considered when choosing a biopsy procedure (device/needle), except for the following cases:

• Vacuum-assisted biopsy (VAB) (43) is the gold standard for evaluating microcalcifications, but in selected cases (lesions larger than 10 mm, etc.) a conventional core biopsy may be sufficient. FNA is not suitable for the diagnosis of calcifications, partly since the effectiveness of sampling (presence of calcification in the sample) cannot be validated.

Organized public health screening: a nationally organized invitation-based screening programme for women with a medium risk aged 45–65, every 2 years in Hungary (other countries: see Table 1) (1, 2, 44–52). (A public health programme initiated by the health care system as a provider, publicly funded or involving population groups considered to be at risk, implemented with a professionally justified frequency.) (53).

Individual (opportunistic) screening: occasional imaging studies of women over the age of 40 years at average risk, with no symptoms suggestive of tumour, no history of breast cancer, for ruling out breast cancer. (Occasional use of methods suitable for recognizing a hidden target condition, related to other medical activities or spontaneously required.)

Assessment methods:

• Physical examination + mammography (medical technician).

Screening of high-risk women (26, 54–59): mutations in the currently known “breast cancer genes” explain 25%–30% of familial breast cancers; other predisposing genes are still unknown. Detection of missing genetic heritability is a central theme of current research (60, 61). Based on this knowledge, it is considered important that in cases of confirmed familial breast or ovarian cancer BRCA1,2 mutation, Li–Fraumeni syndrome, Bannayan–Riley–Ruvalcaba syndrome, Cowden syndrome, Peutz–Jeghers syndrome, and a history of chest radiation administered 10–30 years previously, screening recommendations should also apply to individuals with a breast cancer risk above 20%–25% according to validated mathematical tests. Among mathematical models, the best known are: BRCAPRO, BOADICEA, modified BOADICEA, (2008) Gail, Claus, Tyrer-Cuzick, Myriad I/II and COUCH models. It is advisable to use models that also take into account an extended family history. It should be noted that the National Institute of Health and Care Excellence (NICE) in the UK recommends the use of BOADICEA to decide whether to carry out MRI screening of high-risk patients (62).

Screening recommendation in Hungary for the high-risk group: Above the age of 30 years, mammography (2D digital mammography, or possibly with 3D tomosynthesis and 2D synthetic software) and ultrasound scanning, complemented by annual MRI (when possible), is recommended: at least from the age of 30 years for known BRCA1/2 carriers, and at least from the age of 20 years for those with TP53 mutations (35). Omitting use of mammography screening has to be considered at patients with Li-Fraumeni syndrome, due to the risk of secondary radio-induced malignancies (63).

Hormonal induction (in vitro fertilization programme): Most data in the literature do not support an increased risk of breast cancer after fertility-enhancing hormone treatments, although there is always a theoretical chance of this occurring. Based on individual judgement (mainly after repeated or long-term treatments), annual mammography screening should be considered in women undergoing such treatment (64).

Detailed assessment and individualized screening of patients who have complaints, and of those revealed by screening. The purpose is to establish a maximally accurate preoperative/pre-therapeutic (non-operative) diagnosis (preferably complemented by cytology/histology sampling) in order to optimize the malignant/benign ratio for cases undergoing surgery. According to EU protocol indicators, at least 90% of cases of confirmed malignancy require a preoperative biopsy at the time of diagnosis (35, 65, 66).

In terms of workforce, the recommendation is that all steps of complex breast diagnostics be performed by either one radiologist or as few radiologists as possible, so the diagnosis, based on information provided by each modality and interventions will be as accurate as possible.

Referral to mammography/ultrasonography: since the choice and feasibility of imaging methods required for an individual patient depend on several factors (clinical questions, age, breast size, etc.), it is recommended that the patient be referred for “complex breast assessment” instead of “mammography” and “breast ultrasound”, and the investigating physician should decide what investigations they consider necessary, depending on the clinical question.

Above the age of 30–35 years (age limit should be determined on an individual basis and is the competence of the radiologist):

• Physical examination (physician or certified nurse) + mammography (medical technician).

Under the age of 30–35 years (age limit should be determined on an individual basis and is the competence of the radiologist):

• Physical examination (physician or certified nurse) and ultrasound scanning (67).

Follow-up over time is sufficient only for lesions with a radiomorphology showing a probability of malignancy of less than 2% (BI-RADS category 2 or 3, or stable condition documented for at least 3 years, for solid lesions). If the probability is 2% or more and in the absence of a follow-up history, sampling is mandatory (23). Depending on the type of lesion, follow-up is usually performed in 6-month cycles, for up to 3 years. For inflammatory processes, follow-up in shorter cycles may be justified.

• Physical examination—to be documented: colour, side, amount of discharge, whether it is spontaneous or appears on compression, number or possible localization of discharging ducts, duration (onset, continuous or intermittent, nature of change), other symptoms (e.g., inflammation) and whether the discharge is pathological (28).

In K2, U2 (BI-RADS 2–3) cases, patient at normal risk (no multiple positive family history or confirmed gene mutation), with a sharp-edged, ovoid lesion not larger than 3 cm, having homogeneous structure and a longitudinal axis parallel to the skin surface, containing less than four (macro) lobulations, and displaying no hyperechoic halo sign (81–84).

• Physical examination

Core biopsy is the preferred method. If, however, for any reason, cytology is performed and yields a C2 result but the report does not clearly state a definite diagnosis (e.g., fibroadenoma) the result is not acceptable. For a growing lesion, or if lesion diameter is greater than 3 cm, a core biopsy is recommended.

• If an increase in diameter of more than 20% is observed within 6 months, a core biopsy is mandatory and surgical excision should also be considered, due to the suspicion of a phyllodes tumour (85).

• Physical examination (86–88).

• Physical examination (11).

• For the analysis of questionable calcifications seen on a mammographic image, targeted zoomed or open zoomed images are suitable; there may also be a great need for these in digital mammography or synthetic 2D images (23, 89, 90).

• Physical examination: radial scar/complex sclerosing lesion is almost never palpable, no skin thickening/retraction is seen.

• Physical examination, careful medical history (prior surgery, etc) (23, 90).

• Physical examination, medical history (92).

• Physical examination, medical history.

• In cases of multiple axillary adenopathy, number and size range of lymph nodes showing abnormal morphology should be stated in the radiology report.

• A promising technique for breast cancer is focused ultrasound (FUS, HIFU), a method that can be used with both ultrasound and MRI guidance. Ablation success ranges from 20% to 100%, depending on the type of the FUS system, imaging technique, ablation protocol, and patient selection (102).

• Lesions with uncertain malignant potential (B3 lesions) represent an extremely heterogeneous group with a 9.9–35.1% risk of developing a malignant process (115–117).

Table 2 presents the care protocol based on the “Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions)”. Table 3 shows proposed treatments for the most common lesions under the NHS (UK) protocol.

Before cosmetic surgery (implantation, reduction, etc.): an age-appropriate imaging study should be performed to rule out a space-occupying process.

After breast augmentation for cosmetic reasons: age-appropriate screening/diagnostic tests; the same as for the normal population: mammography (with modified technique for implants: Eklund views, if technically possible), ultrasound scanning and, if necessary, guided sampling. MRI is not required by default for implanted breasts for either screening or diagnostic purposes. The most accurate method for assessing implant integrity is breast MRI. MRI scanning is also the most suitable method when imaging of the space behind the implant is required, but this is considered only in exceptional indications. Axillary silicone lymphadenopathy can be detected reliably by ultrasound, but for the assessment of other lymphatic regions (internal mammary), MRI is the suitable method.

In the event of symptoms, the male breast assessment algorithm is the same as for the female breast. If a breast cancer is present, follow-up after treatment is also the same as for the female breast. Ultrasound scanning is sufficient for instrumental examination of pubertal gynaecomastia. When examining gynaecomastia in adults over the age of 30, mammography should also be performed, complemented by sampling, in doubtful cases.

Breast screening is not required in men without symptoms. Some recommendations suggest regular mammography screening for men at high risk for breast cancer (e.g., carrying BRCA gene mutation) (119–121).

Breast cancer revealed during pregnancy or within 1 year after delivery is called gestational breast cancer.

• For multidisciplinary cooperation, it is desirable to use the following codes in radiology reports: R (1–5), K (1–5), U (1–5). The BI-RADS (0–6) code can also be entered as an option. It should be clearly indicated whether the coding is according to RKU or BI-RADS (Table 4, 5). If the two sides are not identical, the code should be entered separately (right, left) (23).

• Sample handling, cooperation between radiology and pathology.

Aspiration cytology sampling should be performed using a syringe with a rubber stopper. The radiologist performing the sampling should consult the evaluating cytopathologist about the method of smear preparation and fixation, considering that the type of staining used for smear evaluation determines method of fixation, and inadequate smearing may lead to a non-evaluable sample.

• The test order attached to biopsy specimens (preferably a complex radiology report) should include the radiologist’s opinion, as well as relevant clinical data available to the radiologist (e.g., any other tumour disease the patient may have).

After each biopsy, regardless of whether the radiological/pathological/clinical opinions are consistent or contradictory, a written diagnostic “Summary Report” must be prepared. This will be issued by the radiologist performing the biopsy and summarizing tests (after consulting with the pathologist, in questionable cases). The purpose of the diagnostic “Summary Report” is to synthesize the results of different (radiological and pathological) diagnostic methods to facilitate further action and/or a therapeutic decision. Based on the results of the assessment, the breast oncology team gives a therapeutic recommendation, possibly proposing complementary tests; all these are recorded in writing in the “Opinion of the Breast Oncology Team”.

• Ultrasound scanning (35, 65, 66).

• Chest, lungs: chest X-ray, CT.

Bone scintigraphy: a nuclear medicine method based on a radionuclide technique. Planar whole-body scanning is considered to be the standard procedure. Currently, bone scintigraphy may be complemented by single-photon emission tomography (SPECT) or hybrid SPECT/CT measurements, in order to increase diagnostic accuracy (37, 94).

^99mTc phosphonate analogues used for scintigraphy show good bone binding and are rapidly washed out from soft tissues. The sensitivity of the test is 90–100% and specificity is around 50–60%. Increased radiopharmaceutical accumulation can be seen in abnormal, metastatic areas due to increased osteoblast activity and enhanced blood perfusion. Bone scintigraphy usually shows lesions significantly earlier than conventional radiological methods. Due to the method’s relatively low specificity, 18F-NaF PET/CT (bone PET) is increasingly used in countries that are well-equipped with PET systems (35).

PET and SPECT (hybrid forms of PET/CT and SPECT/CT): The essence of these nuclear medicine techniques is that they map the temporal and spatial distribution of selected pharmaceuticals, molecules, drugs, etc. (biomarkers, radiopharmaceuticals, radioligands, tracers, etc.) labelled with PET or SPECT isotopes. Photons emitted from the patient are detected in three dimensions (3D) and quantified, or measured semi-quantitatively. Therefore, in addition to the technical development of these systems, use of various tracers and biomarkers is one of their theoretically unlimited strengths. Incorporation of PET and SPECT cameras and radiological imaging equipment (CT, MRI) into a single machine (PET/CT, PET/MRI, SPECT/CT) has significantly decreased examination time (whole body imaging takes 6–10 min) and amount of radioactivity, as well as enabling simultaneous data collection, accurate measurement and localization of quantitative data of functional molecular maps. As a result, diagnostic accuracy and reliability have significantly improved. As well as increasing the high sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of PET and SPECT tests, the use of hybrid techniques also proved to save time and money and allowed the use of significantly lower activities.

Whole-body-18F-FDG PET/CT: provides whole-body information in a single session at a lower radiation exposure than standard contrast-enhanced CT scan(s), identifies distant metastases with the highest sensitivity, and may help to detect possible second primary tumour(s). During evaluation of post-therapeutic lesions and identification of recurrences, as well as being a highly sensitive method, the extent of the disease and possible progression can be visualized using a lower radiation exposure and in a time-saving manner.

18F-NaF-PET/CT: also called “bone PET” may be chosen as an alternative to bone scintigraphy (29–35). In M-staging, a combined use of 18F-FDG and 18F-NaF tracers provides the highest sensitivity, specificity and diagnostic accuracy.

PET/Magnetic Resonance Imaging (PET/MRI): currently this is primarily used in research (37, 40, 41).

• According to the professional recommendations of the Breast Diagnostic Section of the Hungarian Society of Radiologists, breast imaging tests and image-guided breast interventions may only be performed by a radiologist who has passed the “Complex Radiological Breast Diagnostics” licensure exam (130), with the required minimum technical conditions.

Objective: to update the Hungarian screening model in every direction, to meet European standards and to maximize efficiency (144, 145).

Interdisciplinary National Screening Working Committee: in 2001, the task of the Interdisciplinary Working Committee, set up by the National Chief Medical Officer, was to give an opinion on the reports of screening centres, to participate in the periodic on-site inspection of centres and in inspections prior to licensing. The procedures of the Working Committee need to be renewed, it needs to operate continuously, and it needs to be granted stronger rights. Otherwise, the existence of personal and financial conditions of screening can be assessed only to a limited extent, its effectiveness can only be estimated, without statistical evidence, and the effectiveness of screening may diminish.

We recommend a reasonable adaptation of screening centres (a reduction in numbers, strict quality control), compliance with technical and radiation protection requirements, and support at organization level (regular condition and stability tests, dosimetry).

It is considered necessary to systematically monitorize the collection of statistical data (e.g., registration of prevalence/incidence screening cycles), to assess the effects of screening based on state-of-the-art breast cancer mortality statistics, to ensure follow-up of patients who have been recommended for surgery but who are lost to follow-up (approx. 34%) by possible merger of the EESZT (Electronic Health Service Space) system.

It is considered important to develop a strategy that is effective at increasing participation (reducing the disadvantages of selection bias), maintaining and verifying regular appearance, with the involvement of trained screening statisticians. This is based on rationally designed screening plans (coordinated activity of the screening centre and entity organizing the screening), specification of call lists, monitoring and correction of professional updates and changes.

Rationalization of calls to the same location and time (individual attendance at the same time of the screening interval ±1 month). Consideration of territorial characteristics, seasons, seasonal occupancy aspects, consultation with the creators of lists.

Arranging door-to-door transport via screening coordinators, using funded services of the local bus company. Expected benefit: more comfortable, cheaper travel, better attendance rate.

For conditions and expected results, see EU breast screening indicators and the earlier Hungarian screening-diagnostic protocol (1, 2, 90, 146–148). These previous materials are only partially up to date, and require constant updating by the Interdisciplinary Working Committee.