ADULT FEMALE, 40 YEARS OF AGE OR OLDER, PALPABLE BREAST MASS:

Variant 1: Initial imaging.

1. Mammography diagnostic:

In women 40 years of age or older with palpable breast mass, mammography is the initial diagnostic imaging modality of choice. Both breasts should be imaged in two views; craniocaudal and mediolateral oblique views enabling the entire breast to be completely screened for any additional lesions. The exam should be done under the supervision of a radiologist and a small radiopaque marker can be placed at the site of the palpable abnormality to assess in localizing the lesion.

Remarks: If the patient had a recent mammogram within the last six months, examination of the ipsilateral breast may be considered. Spot compression with or without magnification and supplementary views like exaggerated craniocaudal, cleavage and  90^o medio-lateral views may be needed to clarify the nature or the location of the palpable abnormality.

Strong recommendation

High-Quality Evidence (systematic review of guidelines and cross-sectional studies with a consistent reference standard) [1, 12].

2. Digital breast tomosynthesis diagnostic:

Diagnostic digital breast tomosynthesis (DBT) is recommended as an initial diagnostic tool. A radio-opaque marker can be applied to the skin to indicate its location.

Remarks: Previous studies have demonstrated that DBT is as accurate as digital mammography (DM) in the workup of women presenting with palpable breast lumps aided by its thin section multiplanar capabilities using combined DM and DBT or DM alone.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [13, 14].

3. Ultrasound breast:

Ultrasound of the breast is used following DBT or DM in this age group particularly if the patient has had a negative DM or DBT in the previous six months.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [1, 15]

Variant 2: Mammography findings are suspicious or highly suggestive of malignancy (BI-RADS 4 or 5). Next imaging study.

1. Ultrasound breast:

Breast ultrasound is the next imaging modality of choice to characterize suspicious findings detected by DM or DBT. The ultrasound should be performed using a high-resolution linear transducer with a minimum frequency of 12 MHz and an adjustable focal zone.  Examination of the remainder of the breast and the contralateral breast is recommended to search for any additional suspicious findings.

Remarks: A negative ultrasound examination necessitates stereotactic or tomosynthesis guided biopsy of the suspicious mammographic or DBT finding respectively.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [1, 15, 16]

2. Contrast studies (contrast enhanced mammography/contrast MRI):

In women with dense breasts, contrast mammography (CEM) or contrast MRI are recommended for proper staging and to exclude multicentricity/bilaterality.

Remarks: CEM provides superior imaging performance compared to standard mammography and is considered a relatively affordable accessible imaging tool with a sensitivity approaching MRI.

Conditional recommendation

Moderate-Quality Evidence (observational studies and guidelines) [17-22]

3. Image guided core biopsy:

Core biopsy should be done for assessment and histological evaluation of suspicious palpable breast abnormalities allowing for tumor receptor status. If a suspicious finding seen by mammography of DBT correlates with the palpable abnormality, biopsy is warranted even with a negative ultrasound.  If the lesion is detected by ultrasound, ultrasound-guided biopsy is the preferred approach as it is and more tolerated by the patient as it avoids breast compression and may allow biopsy for difficult to reach locations by stereotactic biopsy. A radio-opaque clip is placed and a  post-biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [1, 23]

4. Image guided fine needle aspiration:

Fine needle aspiration biopsy (FNAB) can be done for the assessment and histological evaluation of suspicious palpable breast abnormalities allowing for faster pathology results but with no difference in therapy timing. A radio-opaque clip is placed and a  post aspiration biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

Remarks: Core biopsy is considered a superior highly sensitive and specific diagnostic method compared to image guided FNAB allowing for tumor receptor status.

Conditional recommendation

Moderate-Quality Evidence (observational studies and guidelines)  [1, 24]

Variant 3: Diagnostic mammography, DBT, and US findings are probably benign (BI-RADS 3). Next imaging study.

1. Mammography:

Breast masses with mammographic features of BIRADS III morphology should undergo 6-, 12- and 24-month surveillance provided that the benign feature of the mass is persistent and there is no upgraded to BIRADS IV or V. Following a 24-month stabilization, the patient will be categorized as definitively benign BIRADS II and resume her normal screening.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [25, 26]

2. Ultrasound breast:

Breast masses with ultrasound features of BIRADS III morphology should undergo 6-, 12- and 24-month surveillance provided that the benign feature of the mass is persistent and there is no upgraded to BIRADS IV or V. Following a 24-month stabilization, the patient will resume her normal screening. If the mass reduces in size or disappear during the 24-month surveillance, it can be downgraded to BIRADS II

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [25, 27]

3. Image guided core biopsy:

Core biopsy is recommended if the mass is newly developed or has shown a 20%  increase in volume or single diameter size. If the lesion is detected by ultrasound, ultrasound-guided biopsy is the preferred approach as it is and more tolerated by the patient as it avoids breast compression and may allow biopsy for difficult to reach locations by stereotactic biopsy. A radio-opaque clip is placed and a  post-biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

Remarks: In some situations, biopsy may be recommended even in probably benign lesions like high-risk patients, patients waiting for organ transplantation, individuals with known synchronous malignancies, or patients attempting to conceive. Moreover, circumstances where a biopsy could relieve a patient's acute anxiety could lead to tissue sampling.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [25, 28]

4. Image guided fine needle aspiration:

Fine needle aspiration biopsy (FNAB) can be done if the mass is newly developed or has shown a 20%  increase in volume or single diameter size allowing for faster pathology results but with no difference in therapy timing. A radio-opaque clip is placed and a  post aspiration biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

Remarks: Core biopsy is considered a superior highly sensitive and specific diagnostic method compared to image guided FNAB.

Conditional recommendation

Moderate-Quality Evidence (observational studies and guidelines) [1, 24]

Variant 4: Mammography findings are benign (BI-RADS 2) at the site of palpable mass. Next imaging study.

1. Ultrasound breast:

When the mammogram shows a benign finding, ultrasound is not necessary considering that there is a certain correlation between the mammographic finding and the clinically palpable abnormality. 

If the correlation is uncertain, a targeted ultrasound examination is recommended.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [1, 29-31]

2. Image guided core biopsy:

If a suspicious finding is detected by ultrasound, biopsy is recommended. A suspicious clinical examination should warrant biopsy irrespective of the imaging findings.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [1, 31, 32]

Variant 5: Mammography findings are negative (BI-RADS 1). Next imaging study.

1. Ultrasound breast:

Ultrasound breast should be done in women with a palpable abnormality and a negative mammogram.

Remarks: Ultrasound increases the detection of both malignant and benign etiologies. In the assessment of a palpable breast mass, the negative predictive value is quite high—more than 97%—when both mammography and US are negative or benign.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [29, 33, 34]

2. Image guided core biopsy:

If a suspicious finding is detected by ultrasound, biopsy is recommended, A suspicious clinical examination should warrant biopsy irrespective of the imaging findings.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [31, 32, 34]

ADULT FEMALE,  30 YEARS OF AGE OR YOUNGER, PALPABLE BREAST MASS:

Variant 1: Initial imaging.

1. Ultrasound breast

Ultrasound is the initial imaging modality of choice preferably targeted to the palpable abnormality.

      Strong recommendation

                  High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference         

             Standard) [35, 36]

Variant 2: US findings are suspicious or highly suggestive of malignancy (BI-RADS 4 or 5). Next imaging study.

1. Mammography diagnostic:

Mammography is indicated if the suspicious ultrasound finding correlates with the clinically palpable abnormality.

       Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [1, 31]

2. Digital breast tomosynthesis diagnostic:

DBT is indicated if the suspicious ultrasound finding correlates with the clinically palpable abnormality. DBT demonstrates the true extent of the lesion and exclude contralateral abnormalities particularly in young women with dense breasts.

       Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [31, 37]

3. Contrast studies (contrast mammography/contrast MRI):

In women with dense breasts, contrast mammography (CEM) or contrast MRI should be recommended for proper staging and to exclude multicentricity/bilaterality.

Remarks: CEM provides superior imaging performance compared to standard mammography and is considered a relatively affordable accessible imaging tool with a sensitivity approaching MRI.

Conditional recommendation

Moderate-Quality Evidence (observational studies and guidelines) [17-22]

4.  Image guided core biopsy:

Core biopsy should be done for assessment and histological evaluation of suspicious palpable breast abnormalities allowing for tumor receptor status. If a suspicious finding seen by mammography of DBT correlates with the palpable abnormality, biopsy is warranted even with a negative ultrasound.  If the lesion is detected by ultrasound, ultrasound-guided biopsy is the preferred approach as it is and more tolerated by the patient as it avoids breast compression and may allow biopsy for difficult to reach locations by stereotactic biopsy. A radio-opaque clip is placed and a  post-biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

      Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [11, 24]

5. Image guided fine needle aspiration:

Fine needle aspiration biopsy (FNAB) can be done for the assessment and histological evaluation of suspicious palpable breast abnormalities allowing for faster pathology results but with no difference in therapy timing. A radio-opaque clip is placed and a  post aspiration biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

Remarks: Core biopsy is considered a superior highly sensitive and specific diagnostic method compared to image guided FNAB allowing for tumor receptor status.       

    Conditional recommendation

                Moderate-Quality Evidence (observational studies and guidelines) [11, 24, 25]

Variant 3: US findings probably benign (BI-RADS 3). Next imaging study.

1. Ultrasound breast:

Breast masses with ultrasound features of BIRADS III morphology should undergo 6-, 12- and 24-month surveillance provided that the benign feature of the mass is persistent and there is no upgraded to BIRADS IV or V. If the mass reduces in size or disappear during the 24-month surveillance, it can be downgraded to BIRADS II

       Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [25-27]

2. Image guided core biopsy:

Core biopsy is recommended if the mass is newly developed or has shown a 20%  increase in volume or single diameter size. If the lesion is detected by ultrasound, ultrasound-guided biopsy is the preferred approach as it is and more tolerated by the patient as it avoids breast compression and may allow biopsy for difficult to reach locations by stereotactic biopsy. A radio-opaque clip is placed and a  post-biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

Remarks: In some situations, biopsy may be recommended even in probably benign lesions like high-risk patients, patients waiting for organ transplantation, individuals with known synchronous malignancies, or patients attempting to conceive. Moreover, circumstances where a biopsy could relieve a patient's acute anxiety could lead to tissue sampling.       

      Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference standard) [11, 25, 26, 38]

3. Image guided fine needle aspiration:

Fine needle aspiration biopsy (FNAB) can be done if the mass is newly developed or has shown a 20%  increase in volume or single diameter size allowing for faster pathology results but with no difference in therapy timing. A radio-opaque clip is placed and a  post aspiration biopsy mammogram or DBT is done to confirm its location and correlation between the ultrasound and mammography/DBT findings.

Remarks: Core biopsy is considered a superior highly sensitive and specific diagnostic method compared to image guided FNAB.

      Conditional recommendation

Moderate-Quality Evidence (observational studies and guidelines) [11, 24, 25, 38]

Variant 4: US findings benign (BI-RADS 2). Next imaging study.

              No further imaging required.

               Strong recommendation

               High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference         

             Standard) [1, 35, 36]

Variant 5: US findings negative (BI-RADS 1). Next imaging study.

            No further imaging required.

Strong recommendation

             High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference         

             Standard) [1, 35, 36]

ADULT FEMALE, 30 to 39 YEARS OF AGE, PALPABLE BREAST MASS.

 Same guidelines as adult female 40 years or older.

Strong recommendation

High-Quality Evidence (systematic review of cross-sectional studies with a consistent reference         

             Standard) [1, 34]

Clinical indicators for monitoring:

Patient file review for the following:

· Proper imaging selection according to the age group.

· Timely initiation of core biopsy procedure in case of suspicious imaging or clinical findings.

· The physician should document follow-up of patients with BIRADS 3 lesions and educate the patient for the importance and the need for follow-up.

These indicators cover aspects such as documentation, diagnostic procedures, and patient education, providing a comprehensive approach to monitoring physician adherence to the clinical guidelines.

Updating the guideline

To keep these recommendations up to date and  ensure  its validity it will be periodically updated. This will be done whenever strong new evidence is available  and  necessitates updating.