Breast Cancer



Breast Cancer


Todd M. Blodgett, MD

Alex Ryan, MD

Barry McCook, MD





Key Facts


Imaging Findings



  • Lesions < 1 cm difficult to detect on whole-body PET/CT or scintigraphy


  • Primary lesion: Focal increased activity on PET/CT corresponding to suspicious mammographic lesion or lesion on ultrasound


  • Metastatic disease: Axillary, internal mammary, and distant lymph nodes (LN); bone, liver, and lung most common metastatic locations


  • PET/CT: Optimal detection of distant metastases in high risk patients; more sensitive for detecting osteolytic bone metastases


  • Recent evidence suggests can proceed to full axillary lymph node dissection when multiple nodes positive in the axilla


  • Refinement of locoregional assessment and detection of occult distant metastases in stage II/III disease


  • Dual time point imaging not universally accepted or used but may be helpful in certain patient populations


Top Differential Diagnoses



  • Infection/Inflammation


  • Trauma and Surgery


  • Lactating Breast


  • Nonmalignant Tumors


Diagnostic Checklist



  • PET/CT excellent for staging patients with potentially aggressive breast cancers and for monitoring response to treatment


  • PET/CT demonstration of osseous metastases usually precludes need for bone scan






Coronal PET shows a focal area of intense FDG activity in the right breast image, which is compatible with this patient’s known history of recently diagnosed breast cancer.






Graphic shows the most common areas of metastatic involvement from breast cancer.


TERMINOLOGY


Abbreviations and Synonyms



  • Ductal carcinoma


  • Lobular carcinoma


  • Breast cancer


  • Breast carcinoma


  • Inflammatory breast cancer


  • Paget disease


Definitions



  • Primary malignancy of breast tissue


IMAGING FINDINGS


General Features



  • Best diagnostic clue



    • Primary



      • Correspondence between suspicious lesion on mammography/ultrasound (US) and focal uptake on FDG PET


      • Incidental focal FDG activity on PET or PET/CT should be further evaluated with mammography/US and biopsy


    • Metastasis



      • Uptake and morphologic changes in axillary, internal mammary, and distant lymph nodes


      • Most common metastatic locations are bone, liver, and lung


  • Location



    • Primary



      • Within breast parenchyma, sometimes including contiguous skin or intramammary lymph nodes


    • Metastasis



      • Location by relative frequency: Axillary lymph node (LN) > internal mammary LN > bone > liver


      • Metastases may be seen in any location, often unpredictable


  • Size



    • Range from microscopic calcifications to large mass


    • Lesions may grow to several centimeters


    • Many smaller lesions not visible on CT or PET


  • Morphology



    • Range of morphologies



      • Microcalcifications



      • Spiculated mass


      • Ill-defined mass


      • Well-circumscribed mass (less common)


Imaging Recommendations



  • Best imaging tool



    • Mammography



      • Still the gold standard for screening


      • Most cases of breast cancer detected on screening exam are stage I; therefore, PET/CT is not cost effective in this group


    • For patients with suspected advanced disease or otherwise deemed “high risk”, consider PET/CT for overall staging evaluation


    • Ultrasound (US)



      • Preferred modality for determining cystic vs. solid nature of suspicious lesions found on mammography


    • Image-guided biopsy



      • US, stereotactic devices, and MR are employed to sample tissue for pathologic evaluation


    • CT



      • Dynamic contrast-enhanced CT for detection of intraductal extension of breast cancer


      • Generally more useful for assessment of spread than for imaging of the primary lesion


      • 3D CT imaging can provide useful information for surgical planning


    • PET/CT: Lymph nodes



      • Twice the sensitivity of CT for abnormal nodal findings in internal mammary and mediastinal regions


      • Improved detection of disease in internal mammary, sub- and interpectoral, supra- and infraclavicular, and Berg level III nodes


      • Although its sensitivity is lower, the PPV of PET is nearly 100% for detecting malignant nodes


      • When axillary lymph nodes are positive on PET/CT, may obviate the need for sentinel lymph node scintigraphy


    • PET/CT: Locoregional disease



      • May help detect multiple primary tumor sites


      • Location of primary in patients with breast cancer metastases and indeterminate mammography


    • Replaces biopsy in patients for whom this is undesirable



      • Increases confidence of locoregional assessment in stage II/III disease


    • PET/CT: Distant disease



      • Whole-body staging is improved, helping to avoid unnecessary surgery


      • Early detection of bony involvement to help avoid fracture


      • Best for detection of osteolytic bone mets (bone scan preferred for detection of osteoblastic mets)


    • PET/CT: Treatment monitoring



      • Baseline tumor SUV can be established for accurate assessment of therapy response


    • MR



      • Modality of choice to evaluate for brain metastases and confirmation of hepatic metastases


      • Also used in some patients to look at bilateral breast involvement in high risk patients


      • Used as a problem solving tool in other patients with dense breasts or other processes in which mammography is less sensitive


  • Protocol advice



    • 10-15 mCi (370-550 MBq) F18-FDG IV


    • Supine whole-body PET/CT, usually with arms up


    • Prone imaging



      • May increase sensitivity when performed following supine study


      • Improved sensitivity for evaluation of breast, axilla, and mediastinum


    • Time point of imaging is controversial



      • Standard is 30-60 minutes after FDG injection


      • Inflammatory lesions can take up FDG more quickly and intensely than tumor, obscuring evaluation of malignant foci


      • Increased uptake of tumor over 1-3 hours


      • Decreasing nonmalignant tissue uptake at these time points


      • Dual-time point imaging may help avoid inaccuracies imposed by several factors



      • Serum glucose, insulin, injection-acquisition interval variability, and partial volume effects may all affect image quality and FDG uptake by cells


      • Use of dual-time point imaging recommended for patients whose breast masses show mild uptake on initial PET images


      • Dual-time point imaging not routinely used


CT Findings



  • NECT



    • Useful for lung & pleural metastases


    • Can also detect lymphangitic spread


    • Suboptimal for organ evaluation


  • CECT



    • Useful for evaluating mediastinal & organ metastases, particularly in the liver


    • Lesions appear attenuating compared with fatty background


    • May show early enhancement on arterial phase on dynamic contrast-enhanced CT


    • Tumors appear as dense lesions on CT and usually show early contrast enhancement similar to that seen with dynamic MR


    • CT performance parameters



      • Sensitivity, specificity, and accuracy in detecting intraductal spread or DCIS: 71.9%, 83.3%, and 76.0%


      • Sensitivity, specificity, and accuracy for diagnosing muscular invasion: 100%, 99%, and 99%


      • Sensitivity, specificity, and accuracy in diagnosing skin invasion: 84%, 93%, and 91%


      • Sensitivity rate for microcalcifications: 59%


      • 3D CT shown to depict and define extent of nearly all tumors in most patients


Nuclear Medicine Findings



  • PET/CT: General



    • Sensitivities for PET and PET/CT range from 80-90% for evaluation of primary tumors



      • Lower sensitivity for smaller primary lesions


      • 60-80% sensitivity for lesions ≥ 2 mm


      • Prone PET/CT may allow detection of smaller lesions (5-7 mm)


    • Superior resolution may be afforded by positron emission mammography (PEM), which can detect lesions as small as 2 cm



      • Sensitivity 90% and specificity 86%


      • Still investigational


    • High lesion SUV seen in



      • Larger invasive tumor


      • Higher histologic grade, mitotic counts, and nuclear atypia


      • Absence of hormone receptors


      • Presence of c-erbB-2 expression


      • Metastasis to lymph nodes


      • Infiltrating ductal type (vs. infiltrating lobular type)


  • Initial Diagnosis



    • PET/CT is not recommended for initial diagnosis but may be helpful in select patient populations or when standard modalities are ineffective



      • Consider for occasional use in patients with implants


      • Dense breast tissue can render mammography nondiagnostic


      • Cross-sectional morphologic imaging may be equivocal


    • Lower FDG uptake seen in well differentiated and lobular carcinomas compared to other breast cancers



      • Normal-range SUV in these malignancies can lead to false negatives


      • If CT shows a spiculated enhancing mass with low level FDG activity, may represent non-FDG-avid malignancy


    • Tubular cancer may also have have low FDG uptake


    • High grade DCIS may be positive on PET if > 1.5-2.0 cm


    • Tumors with higher tendency to relapse often have SUV above 3.3-4.0


  • Staging



    • Overall, whole-body PET/CT limited in detection of < 8 mm lesions


    • Although not currently recommended for axillary nodal evaluation, positive axillary lymph node on PET/CT has high PPV for malignancy


    • Characterization of axillary metastases depends on several factors



      • Size and number of lymph nodes


      • PET/CT has lower sensitivity of 60-80% for axillary mets


      • FDG PET can provide resolution only to level of 6-8 mm lesions


      • Optimal axillary staging depends on sentinal LN biopsy


    • Evaluation of internal mammary and mediastinal lymph nodes



      • PET/CT superior for detection and localization (vs. CT and MR)


      • Accurate staging of these lymph node stations is crucial for prognosis and therapy


    • PET/CT has 80-95% sensitivity for detecting distant metastases at the time of initial diagnosis



      • NPV > 70-90%


      • PPV lower due to confounding factors such as infection, inflammation, etc.


    • NPV and PPV both benefit from combined modality PET/CT or MR fusion


    • Detection of hepatic metastases



      • Combination of low density lesion on CT and increased uptake on FDG PET is highly suggestive of malignancy


      • MR can clarify cases with positive FDG PET and negative CT


      • False negatives may be seen with subcentimeter lesions and low density lesions with nonelevated FDG uptake


      • False positives most often due to infection/inflammation or interposed colon


      • Occasionally seen incidentally on bone scan


    • Detection of osseous metastases



      • Consideration should be given to performing both bone scan and FDG PET/CT at initial staging in high risk patients


      • Information complementary in breast cancer osseous metastatic assessment



      • Lytic and trabecular metastases are detected with high sensitivity > 90% on FDG PET


      • Blastic lesions poorly seen on PET but can be detected on CT


      • Bone scan is preferred for detection of cortical blastic metastases but has poor sensitivity for lytic or trabecular metastases (75-80% and < 50%)


    • Effect on management: FDG PET or PET/CT may change patient management up to 51% of the time


    • PET/CT plays an increasingly important role in radiation therapy planning



      • Pre-treatment planning or follow-up with PET/CT benefits 40-60% of patients in multiple studies


  • Restaging



    • Overall, FDG PET has equal or better accuracy for restaging compared to conventional imaging


    • Combined PET/CT offers higher sensitivity and specificity than PET alone


    • False positives due to prior lymphadenectomy



      • Surgical site may remain positive for 3-12 months


      • Inflammation may persist surrounding clips or sutures


    • FDG PET is superior to conventional imaging for diagnosis of metastatic disease (87-90% vs. 50-78%)



      • In patients with rising serum tumor markers and asymptomatic breast cancer


  • Response to Therapy



    • SUV response has proven an accurate indicator of treatment response


    • Major criterion for good treatment response is approximately 50-60% reduction in SUV following 2 cycles of chemotherapy



      • > 55% reduction after 1 cycle portends good clinical response


      • Increase in SUV 7-10 days after antiestrogen therapy may occur due to a metabolic flare


      • Typically associated with good response


    • Detection of poor response is equally valuable



      • Early institution of alternate therapy


      • Side effects are minimized from inadequate treatments


Other Modality Findings



  • Positron emission mammography (PEM)



    • Investigational modality


    • F-18 used as radiotracer


    • Improves accuracy for primary lesion detection


  • F-18 fluoride PET/CT



    • Superior to traditional bone imaging agents (Tc-99m MDP)


    • Pending resolution of reimbursement and FDA issues


  • F-18 estradiol compounds demonstrate whether malignant lesions are estrogen receptor (ER) positive (investigational)


  • F-18 L-thymidine demonstrates tissue with high DNA turnover (investigational)


DIFFERENTIAL DIAGNOSIS


Infection/Inflammation



  • Generally lower SUV-to-background ratio than equalsized tumors


  • Granuloma-producing disease (e.g., sarcoidosis)


  • Soft tissue infection (e.g., esophagitis, abscess)


  • Atherosclerosis


  • Sites of surgical intervention (e.g., resection, ostomy sites)


  • Intramuscular injection sites


  • Degenerative bone disease


  • Non-puerperal mastitis


Trauma and Surgery



  • Inflammatory uptake related to surgical procedures last 3-6 months


  • Uptake can be due to hematoma


  • Scar tissue may demonstrate uptake indefinitely


  • Traumatic fracture and soft tissue injuries (e.g., lytic bone metastases)


Fibrocystic Disease



  • Low level FDG uptake may be seen in multiple focal sites


Nonmalignant Tumors



  • Fibroadenoma, papilloma, and others


  • Characterized by low level FDG uptake



    • Hypercellular benign tumors may show increased uptake


Lactating Breast



  • Glandular tissue may show intense FDG uptake


  • May see patchy areas of intense FDG activity


  • History is critical to reduce misinterpretation


Normal Breast



  • FDG uptake more intense with increasing breast density


Other Malignancy



  • Second primary neoplasm (e.g., thyroid, lung, colon, etc.)


  • Primary breast lymphoma


Implants



  • Inflammatory response to silicone or saline leakage can produce positive PET



    • Silicone > saline


  • Calcifications can produce inflammatory uptake or AC artifact (in the case of bulky calcification)


PATHOLOGY


General Features



  • General path comments: Higher SUV correlates with higher density of viable cancer cells


  • Genetics



    • Increased incidence with close family history (e.g., mother, sister)


    • > 80-85% breast cancer occurs in absence of family history



    • BRCA-1, BRCA-2



      • Genetic mutations present in ˜ 0.5% of population


      • Confer 3-7x risk of developing breast cancer compared to women without these mutations


      • BRCA-2 may increase breast cancer risk in men


  • Etiology



    • Risk factors



      • Age


      • Family history


      • Personal history


      • Early menarche


      • Late menopause


      • Postmenopausal obesity


      • Radiation exposure (greatest risk with external beam)


      • Alcohol ingestion


      • Hormone replacement therapy


    • Full-term pregnancy at early age reduces risk


  • Epidemiology



    • Most common cancer in women



      • Second to lung as most common cause of cancer death


    • Lifetime risk in women for breast cancer: 13.2%



      • With BRCA mutation: Up to 85%


Microscopic Features



  • Ductal cancers (arising from ductal cells)



    • In situ: Ducts containing tumor cells with no stromal invasion


    • Invasive: Tumor penetrates ductal epithelium and invades stroma


  • Lobular cancers (arising from lobule cells)



    • In situ: Lobules containing tumor cells with no lobule wall penetration


    • Invasive: Stromal invasion by tumor cells


Staging, Grading, or Classification Criteria

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Sep 22, 2016 | Posted by in MAGNETIC RESONANCE IMAGING | Comments Off on Breast Cancer

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