Medical School Lecture Breast Imaging Medical School Lecture November 18, 2015 Susan Peddle, MD Assistant Professor University of Ottawa introduction and overview of the WBHC

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Overall Objectives Review the background and evidence supporting the use of screening mammography, ultrasound (US) and magnetic resonance imaging (MRI) Describe Canadian population‐based screening programs, their performance indicators and their costs Provide an overview of mammographic abnormalities and their work‐up

Objectives Screening versus Diagnostic mammography BI-RADS Review of mammographic abnormalities that warrant further work-up Diagnostic work-up Features of benign versus malignant lesions on ultrasound Breast Intervention Role of MRI in breast imaging Current recommendations for breast screening

Objective 1 Screening versus Diagnostic mammography

Screening MG versus Diagnostic MG Screening MG: to find cancers smaller than those detected at BSE or CBE Sensitivity of BSE: Unknown Sensitivity of CBE: Unknown Sensitivity of screening MG: 75-90% Diagnostic MG: to further evaluate a screen detected abnormality, symptom or clinical finding Pain Palpable lump Nipple Discharge Others (skin changes, nipple inversion, shrinking breast, enlarging breast) BSE = breast self exam CBE = clinical breast exam as performed by a medical professional

subareolar lactiferous ducts Mammographic Anatomy lymph node skin pectoralis muscle vessel glandular tissue subareolar lactiferous ducts Every breast has different a composition and relative amounts of fat versus more dense fibroglandular tissue Our ability to detect abnormalities is dependent on composition fat inframammary fold Cooper’s ligaments

Typical Mammography Unit

Routine Mammographic Views MLO CC

We have to apply maximal compression, which only lasts momentarily, to obtain the best view and minimize overlap

MLO CC Outer quadrant Upper quadrant Inner quadrant Lower quadrant goal of CC is to maximize visibility of medial breast  techs document if patient anxious or would not allow compression Inner quadrant Lower quadrant

O’clock Position used for Localization Right Breast Left Breast 12:00 12:00 Lat 9:00 3:00 Med Med 3:00 Lat 9:00 6:00 6:00

Technical Limitations Breast Density Patient anxiety, discomfort, physical limitations Post-therapeutic changes goal of mammo to pull out breast tissue - these things prevent that

Breast Density fatty replaced 0-25% scattered 25-50% heterogeneous discuss how x-rays work the reason we see things is because two tissues or variable densities are adjacent to each other the best we have, but far from perfect all MG reports comment on breast density to set the stage heterogeneous 50-75% extremely dense 75-100%

Objective 2 BI-RADS

BI-RADS Breast Imaging Reporting and Data System Helps achieve uniformity in breast imaging reports which improves their clinical utility by communicating findings in a standardized way Help determine clear management

BI-RADS 0: Needs further evaluation 1: Normal 2: Benign finding 3: Probably benign 4: Suspicious abnormality 5: Probable cancer 6: Biopsy proven cancer

0: Needs further evaluation - additional mammographic views, +/- US, +/- MRI 1: Normal - Return to screening 2: Benign finding - Return to screening 3: Probably benign - > 98% likelihood of being benign. Short interval follow-up recommended in 6 months. 4: Suspicious abnormality - Biopsy needed 4A - 10-50% likelihood of being malignant 4B - 50-95% likelihood of being malignant 5: Probable cancer - Biopsy and surgical consultation needed (> 95% likelihood of being malignant) 6: Biopsy proven cancer

Objective 3 Review of mammographic abnormalities that warrant further work-up

4 Main Mammographic Abnormalities Microcalcifications Architectural distortion Mass Asymmetries

Microcalcifications

Microcalcifications image Microcalcifications can be an indicator of cancer, although they are often benign Detected mammographically Characterized by morphology (appearance), distribution, and change over time Analysis helps radiologist determine the likelihood of underlying benign versus malignant pathology image

Terminal Ductal Lobular Unit (TDLU) Basic functional unit in the breast Consists of 10-100 acini that drain the terminal duct Terminal ducts drain to larger and larger ducts, and eventually to the nipple

TDLU - site of origin of most cancers

Lobular Calcifications - form in acini - Intraductal Calcifications - form in ducts - Due to calcified cellular debris or secretions Almost always benign Suspicious for malignancy

Benign Calcifications Skin Coarse or “Popcorn” Vascular Rim or “Eggshell”

Suspicious Microcalcifications “Variable in size, density and shape” Fine Pleomorphic

Suspicious Microcalcifications “Thin, linear or curvilinear irregular” Fine linear or branching

Architectural Distortion

Architectural Distortion Normal architecture is distorted with no definite visible mass Look for abnormal straight lines or spiculations radiating from a point Differential diagnosis: Carcinoma vs scar tissue

Right - recurrence with IDC Left - IDC prior lumpectomy on right compare to previous very important scar - increasing in density or changing in any way - further evaluation essential

Right - recurrence with IDC Left - IDC

Mass

Mass A space occupying 3D lesion seen in two different projections 3 important descriptive terms: Shape Margin Density

Benign features Suspicious features Round or oval Circumscribed Low density Suspicious features Irregular Microlobulated, indistinct, spiculated High density

Typically Benign

Typically Malignant

Asymmetries

Asymmetries Unilateral deposits of fibroglandular tissue with NO mirror-image correlate in the opposite breast A discrete mass is not seen on the initial MLO and CC views True pathology versus overlapping normal tissue?

Asymmetry ??

Rt MLO Lt MLO

Focal Asymmetry

Global Asymmetry

Objective 4 Diagnostic work-up

“Work-up” Refers to additional testing required to determine the origin of an imaging or clinical abnormality Comprised of additional mammographic views, US, MRI and/or biopsy

Abnormal Mammogram ? True abnormality Additional mammographic views ? Mass +/- Ultrasound ? Suspicious +/- Biopsy

Additional Mammographic Views Straight lateral or 90 degree view Coned compression views Magnification views Pinched (Eklund) views Rolled view Extended CC view Cleavage view Tomosynthesis

Magnification Views Performed for better characterization of microcalcifications Focal spot = 1.6 times 2 views: CC and straight lateral (90 degree)

Lt MLO Magnification View Malignant Calcifications: Tightly clustered. Vary in size and shape. Bizarre branching irregular or linear forms Typically found in DCIS and Invasive Ductal When suspicious calcifications are the only sign of malignancy one may suspect DCIS but invasive ductal can not be excluded by mammography alone. LCIS and Invasive Lobular Cancer do not typically calcify.

Coned Compression Views Performed to differentiate normal overlapping parenchyma from a true abnormality

Coned Compression Lesion does not persist on coned compression views in keeping with normal fibroglandular tissue

Coned Compression Views Lesion persists on coned compression views in keeping with a true lesion

Ultrasound confirms the presence of a mass suspicious for malignancy

Tomosynthesis - New technique created to produce a 3D picture of the breast using X-rays - Designed to reduce overlapping tissues in mammography - Results in high-resolution images at mammographic doses

Tomosynthesis 3D 2D Breast Reconstructed planes If a 2 D image is taken the ovelapping structures, such as a cancer with normal breast tissue, will be difficult to differentiate from each other. X-ray tube moves in an arc across the breast This may lead to false positives and false negatives. With tomosnthesis, the exposures are obtained over a 15 degree arc , an exposure taken every 1 degree yielding 15 individual exposures You need small angle for rapid scan without motion artifact. Objects at different heights in the breast are projected differently at different angles. Projection images are reconstructed to show 1 mm slices of breast tissue. This allows for separation of overlapping structures, and allows for accurate separation of lesions, permitting differentiation of true lesions from underlying tissue. Reconstructed planes

Stationary breast platform X-ray tube swings during tomo Breast tomosynthesis is an imaging technology that acquires 2D projection images of a compressed breast at multiple angles during a sweep of the X-ray tube. ARC ABOVE THE BREAST

Tomosynthesis

Objective 5 Ultrasound features of benign versus malignant lesions

Ultrasound how US works - sound transmission real time visibility allows physical examination at time of imaging

Benign vs Malignant Features

Simple Cyst Always benign Features: Anechoic (black) No wall “Through transmission” talk

Ultrasound Features of Solid Masses benign - slow growing, so smooth, pushing borders Classic benign Classic malignan t

Benign Breast Lesions Well circumscribed - doesn’t invade Wider than tall - obeys normal tissue planes Thin echogenic pseudocapsule - compresses adjacent tissue Gentle macrolobulations Intensely echogenic - contains fat

Malignant Breast Lesions Angular margins Spiculations Microlobulations Taller than wide Posterior shadowing Ductal extension/Branch pattern Microcalcifications

Margins: Angulated

Margins: Microlobulated

Ductal extension

Shadowing

Can we make the diagnosis of cancer based on ultrasound features only?

Case 1: 83 yo, palpable mass medial left breast Case 2: 88 yo, palpable mass UOQ left breast

Case 1: 83 yo, palpable mass medial left breast Case 2: 88 yo, palpable mass UOQ left breast Cancer Fibroadenoma

Invasive ductal carcinoma Involuted calcified fibroadenomas

Always start with a MG in women 35 years old and greater!

Objective 6 Breast Intervention

Breast Intervention Tissue diagnosis mandatory for diagnosis of breast cancer In the US, 1 million breast biopsies are performed annually to diagnose 200,000 breast cancers Avoids unnecessary benign surgical excisions and allows surgeons to plan appropriate surgery in the setting of cancer Extremely beneficial for patients and for the health care system in general old school - patient had a lump and it was surgically removed Not so now as our goal is to do the right surgery once to minimize the need for re-excision and to deal with the axilla ( a very hot topic) the first time expedites adjuvant treatment - ie chemo or radiation post-operatively cost of one biopsy is far less than the cost for a surgical excision in the OR

Breast Intervention How do we perform breast biopsies? Ultrasound guided biopsy Solid and complex solid-cystic masses Stereotactic biopsy Suspicious or indeterminate microcalcifications seen on MG Persisting suspicious asymmetries on MG with no sonographic correlate MRI guided biopsy Lesions identified only on MRI with no mammographic or sonographic correlate preference is US biopsy - fast, relatively cheap, more comfortable for patient and allows real-time visibility

Ultrasound Guided Biopsy

Fine needle aspiration FNA (uncommon) CNB VAD Fine needle aspiration Core Needle Biopsy Vacuum-assisted Device

Core Biopsy

Vacuum Assisted Biopsy

Stereotactic Guided Biopsy

Technique Scout image taken to locate lesion in biopsy window “Stereo Pair” obtained after moving x-ray tube +15° and −15° relative to 0° position X, Y and Z (depth) coordinates calculated by computer Lots of vendors are needles Key - understand the basic physics of your device

Specimen radiograph confirms microcalcifications in the specimen Final diagnosis: DCIS

Persisting focal asymmetry Pre biopsy Persisting focal asymmetry Post biopsy

Deploy marker clip at the site of biopsy

Preoperative Image Guided Localizations

Preoperative Image Guided Localizations Pre-operative localization is used to ensure complete excision of nonpalpable breast lesions Localization device is inserted pre- operatively using mammographic or ultrasound guidance Helps guide the surgeon in the OR, improving clear margin and breast conservation rates

MG or Ultrasound Guidance

46 yo - Multifocal Disease UOQ

2 wires inserted to guide surgical excisions

Radioactive Seed Localization Low-dose I125 titanium prostate seed is placed at the target using mammographic or ultrasound guidance Surgeon uses radioactivity probe to localize, dissect and remove breast lesion Image courtesy of The Mayo Clinic

X-ray of lumpectomy specimen to confirm excision Post-procedure mammogram confirms accurate seed placement adjacent to clip X-ray of lumpectomy specimen to confirm excision

Objective 7 Role of MRI in breast imaging

Role of MRI in Breast Imaging MRI has a high sensitivity Main roles include: High risk screening: BRCA 1 and 2 mutation carriers > 25% lifetime risk of developing breast cancer Radiation to anterior chest wall for treatment of lymphoma Local staging of breast cancer Assess response to chemotherapy Problem solving

43 yo – BRCA1 carrier June 20, 2012

Baseline Screening MRI Bilateral breast cancer not seen mammographically 08041733 BILATERAL BREAST CANCER IN BRCA 1 GENE BASELINE MRI

Click View then Header and Footer to change this footer Local Staging with MRI MLO CC Left breast Clinical: • Upper outer quadrant • Palpable abnormality MG: • Pleomorphic microcalcifications (BI-RADS 5) Stereotactic Biopsy: Final diagnosis: DCIS high grade Click View then Header and Footer to change this footer

2 min C+ MRI: • Non mass enhancement (arrow) • Additional retroareolar mass (circle) for which US guided biopsy was performed Mastectomy and SLNB were both performed Final pathology: Invasive ductal carcinoma and ductal carcinoma in situ (DCIS) (Total extent 8.0 cm) 2 min C+ 2 min MIP

Assess response to chemotherapy with MRI January 2012 July 2012 Post 6 cycles of chemotherapy

Objective 8 Current recommendations for breast screening

Current Recommendations for Screening Who should have mammograms? At what age should screening be initiated?

Benefits of Screening Mammography - Reduction in breast cancer mortality by 40% - Lower rate of mastectomy, radiation therapy and axillary lymph node dissection - Less expensive treatment and less time off work

Limitations of Screening Mammography...”Harms” False Negatives 10-20% of breast cancers are only detected at breast self-exam or physical exam False Positives Only 5-40% of lesions are detected at screening and recommended for biopsy Over-diagnosis 11% of cancers found never progress False positives - number of cases detected on screening which lead to biopsy but turn out to be benign 10% recalls per rad - 2% need biopsy of those 40 % cancer, 60% benign - so 1.2% “unnecessary biopsies”

CAR Guidelines – Screening Mammography Asymptomatic women 40-49 years - Annual screening MG Asymptomatic women 50-74 years - Every 1-2 years Women over 74 years - Every 1-2 years, if in good health in accordance with ACR

When to Start Screening? - CTFOPH recommends screening women 50-74 and having a discussion about screening with women 40-49 - OBSP screens women 50-74 - Canadian Association of Radiology, American Cancer Society, National Comprehensive Cancer Network, American College Radiology, College Obstetricians and Gynecologists, recommend screening women 40-74 + Canadian Task Force on Preventative Health - published in 2011 Extremely controversial and flawed - no breast cancer specialists; old, out-of -date machinery and single view mammograms used; epidemiologists implementation of the CTFOPH guidelines may save money each year on screening costs, the result will be thousands of unnecessary breast cancer deaths

Should I Screen after age 74? - For all ages, the mortality benefit from mammographic screening begins to be seen 5-7 years after the onset of screening - Mammographic screening can be continued as long as there is reasonable expectation of a life expectancy of at least seven years - Average life expectancy for an 80 year-old woman is 8.6 years which means that the healthiest quartile can be expected to live considerably longer

What is the Chance of Developing Cancer between 40-50 years old? - 1 in 69 women will be diagnosed with invasive breast cancer in their 40s - Breast cancer is the leading cause of cancer death in women < 50 years - There is a very low incidence of breast cancer below age 30 There is no abrupt change at age 50 Annual U.S. breast cancer incidence rates per 100,000 women as a function of age for invasive + in-situ cancers

Numbers of Breast Cancers by Age 5% < 40 yrs 18% 40-49 yrs 23% 50-59 yrs 26% 60-69 yrs 28% 70-79 yrs 18% 40 - 49 years 20% for every decade > 40 yrs 77% > 50 years SEER, 2010, http://seer.cancer.gov/csr/1975_2007/

No Role for Screening with Ultrasound Average risk women - Screen with mammography High risk patients - Screen with mammography and MRI

Objectives Screening versus Diagnostic mammography BI-RADS Review of mammographic abnormalities that warrant further work-up Diagnostic work-up Features of benign versus malignant lesions on ultrasound Breast Intervention Role of MRI in breast imaging Current recommendations for breast screening

Thank you a special thanks to all the technologists at the breast centre for their expertise I truly feel fortunate to work with such an incredible team