Challenge in Breast imaging: volumetric analysis of tumor/breast ratio Catherine Appleton, MD Chief, Breast Imaging Section Mallinckrodt Institute of Radiology

Background Breast Cancer is very common Mastectomy versus Breast Conservation Therapy (BCT) Patients must be carefully selected for BCT Breast size Tumor size Multi-focal? Quantitative vs. Qualitative?

The Problem Variable outcomes in aesthetic results Some patients more “motivated” than others Judgment varies among surgeons Radiation may contribute to unpredictable results

Proposed Solution Develop formula to better select patients for BCT Tumor size/volume::Breast size/volume Density Limitations Mammography compression Some tumors easier to measure than others Mammographic density Tumor type Discrepancy between imaging/pathology

Clinical Need Software/programming solution Automate (or partially automate) breast and tumor volumes from a mammogram Select ROI  calculate What we know… Breast thickness from compression Clear margins of breast tissue based on anatomy Variables Tumor size may not be reproducible Density** Could use 2D or 3D (tomosynthesis)

Image Samples

BILATERAL DIAGNOSTIC FULL-FIELD DIGITAL MAMMOGRAM BILATERAL BREAST ULTRASOUND. DATE: 07/21/08 HISTORY: Palpable mass on the right. This patient has a strong family history of breast cancer. She has three cousins who died of breast cancer and a sister who died of breast cancer. She has not had a mammogram in seven years. She feels something palpable on the right. A radiopaque marker was placed overlying the area of patient concern and standard images of both breasts were obtained. A focal asymmetry was identified inferior and slightly medial to where the patient indicated and spot magnification views of this region were performed. The patient has scattered fibroglandular tissue bilaterally. In the upper outer right breast is a 16 mm spiculated mass. Ultrasound of this region disclosed the presence of a hypoechoic, irregular mass with shadowing. This is highly suggestive for malignancy. Interrogation of the right axilla showed the normal appearing lymph nodes. The opposite breast is negative. Computer-aided detection was used for interpretation. OVERALL FINAL ASSESSMENT: BI-RADS Category 5: Highly suggestive of malignancy. The patient is being referred for ultrasound-guided core needle biopsy. Her primary care physician will be contacted and an appointment will be made with the Breast Surgeon.

EXAMINATION: 1. MRI EXAMINATION OF THE BREASTS WITH AND WITHOUT CONTRAST 2. 3D POST PROCESSING ON A DEDICATED 3D WORKSTATION DATE OF EXAMINATION: 08/07/2008 HISTORY: 66-year-old female who presented with a palpable abnormality in the right breast on 07/21/2008. Mammography demonstrated an irregular, spiculated mass in the right upper-outer quadrant. Biopsy on 07/28/2008 revealed invasive mammary carcinoma and DCIS. Breast MRI is performed to evaluate extent of disease. DATE OF LAST MENSTRUAL PERIOD: Postmenopausal TECHNIQUE: MRI examination of the breasts per breast tumor protocol with and without gadolinium contrast. The images were transferred to a breast CAD system for 3D post processing and contrast kinetics analysis. Estimated GFR: 30-60 ml/min/1.73 square meters Creatinine: 1.1 mg/dL on 08/07/2008 Contrast: Multihance, 20 cc (single dose) COMPARISON: Mammogram 07/21/2008 and postbiopsy mammogram 07/28/2008. BACKGROUND ENHANCEMENT: Mild: 25-50%. FINDINGS: Exam is limited by patient motion. Left breast: No evidence of suspicious mass or suspicious abnormal enhancement. No abnormally enlarged left axillary lymph nodes. Right breast: In the upper-outer quadrant at 10-11:00, there is an irregular mass with spiculated margins measuring 18 x 22 x 27 mm. The mass is 3 cm from the nipple, demonstrates homogeneous enhancement and predominantly washout kinetics. There is a smaller satellite lesion which is 2 cm posterior to the larger mass. This is an irregular mass with irregular margins measuring 11 x 11 x 15 mm at 10-11 o'clock, 7 cm from the nipple. This mass also demonstrates homogeneous enhancement and prominently washout kinetics. There may be nonmasslike enhancement surrounding these masses, but this is difficult to assess due to motion. Total extensive disease is approximately 59 mm. No abnormally enlarged right axillary lymph nodes. IMPRESSION/RECOMMENDATIONS: Left breast: Negative. Right breast: BI-RADS Category 6: Known biopsy-proven malignancy. 1. Irregular mass at 10-11 o'clock measures 18 x 22 x 27 mm, roughly correlating with size on mammogram. 2. Satellite lesion 2 cm posterior to the larger mass measures 11 x 11 x 15 mm. If breast conservation therapy is desired, then targeted ultrasound and biopsy of this lesion can be performed. OVERALL FINAL ASSESSMENT: BI-RADS Category 6: Known biopsy-proven malignancy.

EXAM: RIGHT BREAST BRACKET WIRE LOCALIZATION UTILIZING DIGITAL MAMMOGRAPHIC GUIDANCE AND SURGICAL SPECIMEN RADIOGRAPH. DATE: Sep 18, 2008 8:58:00 AM HISTORY: 66-year-old female who presented with a palpable 16 mm mass in the upper-outer quadrant of the right breast, status post ultrasound guided biopsy on 07/28/2008, which revealed invasive mammary cancer and ductal carcinoma in situ. A possible satellite lesion was identified on the breast MRI. The patient underwent MR guided biopsy on 09/11/2008 of the satellite lesion which revealed ductal carcinoma in situ. Right breast bracket needle localization is requested prior to surgical excision of both lesions. PROCEDURE AND FINDINGS: The procedure was discussed with the patient. After sterile preparation of the skin, the breast was placed in a compression grid, and 1% lidocaine was utilized for local anesthesia. Two hook-wire systems were advanced into the areas of interest in the breast from a lateral approach utilizing digital mammographic guidance. Orthogonal views were obtained to confirm appropriate needle/wire position. The patient tolerated the procedure well and there was no evidence of immediate complication. The images were marked for the surgeon, and the patient was transferred to the operating suite for surgical excision. A surgical specimen was subsequently received from the operating room and digital radiography was performed. The lesions of interest with microclips are included within the surgical specimen. These findings were communicated to the surgeon. The attending radiologist, Dr. Lee, was present throughout the entire procedure. Addendum # 1 by Michelle Lee, M.D. on 09/23/2008 11:49 AM ADDENDUM: For clarification in the history provided above, the MR guided biopsy of the possible satellite lesion 09/11/2008 reportedly demonstrated PRELIMINARY pathologic diagnosis of ductal carcinoma in situ. However, the final pathology report demonstrated intraductal papilloma (small/peripheral subtype; extensive and multifocal; unusual cribriform appearance), usual ductal hyperplasia, microcysts, microcalcifications, and no atypical or malignant findings. This is a high risk lesion which warranted surgical excision at the time of the patient's lumpectomy.

EXAM: BILATERAL FULL FIELD DIGITAL DIAGNOSTIC MAMMOGRAM WITH CAD AND BILATERAL BREAST SONOGRAM DATE: Sep 9, 2008 HISTORY: 54-year-old female who reports trauma to the right breast 2 months ago and a palpable abnormality in the right breast subareolar region for approximately 6 weeks. COMPARISON: This is the patient's baseline mammogram. BREAST PARENCHYMAL COMPOSITION: There are scattered fibroglandular densities. FINDINGS: Full field digital craniocaudal and mediolateral oblique views of both breasts were obtained. Computer Aided Detection was performed with R2, version 8.3. Right breast: There is an irregular mass with spiculated margins and associated heterogeneous microcalcifications in the subareolar region. The mass is associated with nipple retraction and measures 21 x 21 mm. Ultrasound examination was subsequently performed for further evaluation. Ultrasound of the right breast periareolar region and right axilla were performed. In a subareolar region at 2:00, there is an irregular, hypoechoic mass with posterior acoustic shadowing and antiparallel orientation. There is nipple retration on clinical exam. The mass extends to the under-surface of the nipple. The mass measures at least 20 x 18 x 16 mm on ultrasound. In the low right axilla, there are multiple abnormal lymph nodes with thickened cortices; these are highly suspicious for metastatic disease. Left breast: There is a circumscribed and partially obscured, equal density, oval mass at 3:00 measuring approximately 9 mm. Ultrasound examination was subsequently performed for further evaluation. Ultrasound of the left outer breast was performed. No focal abnormal solid or cystic lesion is seen in the vicinity of the mammographic mass. OVERALL ASSESSMENT: BI-RADS Category 5: Highly suggestive of malignancy. 1. There is an irregular, spiculated mass in the right breast subareolar region. There are multiple abnormal lymph nodes in the right axilla. Ultrasound guided core needle biopsy of the mass and fine needle aspiration of the axillary lymph nodes is recommended. The patient underwent a same-day biopsy which is dictated seperately; please see that report for details. 2. There is a benign-appearing oval mass in the left breast seen on the mammogram. There is no sonographic correlate. Pending histologic resolution of the highly suspicious RIGHT breast mass, this lesion can be evaluated with MRI (should the patient undergo MRI following a diagnosis of breast cancer.) Alternatively, this lesion can be subjected to serial 6 month follow-up given it benign features, and the lack of prior studies to document stability. OVERALL FINAL ASSESSMENT: BI-RADS Category 5: Highly suggestive of malignancy. The patient has been given an appointment with Dr. Margenthaler in surgery on 9/16/08. Addendum # 1 by Catherine M.D. Appleton on 09/10/2008 5:45 PM Findings and recommendations were discussed with Dr. Michael Johnson, MD at the People's Health Center by Mary Ellen Swatske, RN on 9/10/08 at 3pm.

MIP

MIP

First post-contrast subtraction

Conclusion Currently have acceptable results but there is room for improvement Would a pre-operative tumor/breast ratio optimize patient selection/surgical management? Study protocol will follow women with 3D photographic imaging to correlate with radiology imaging Automated software solution needed…