Breast MRI: Friend or Foe? Comments: 0 ASSOCIATED PRESS 8/19/2008 - PowerPoint PPT Presentation

APPLEGATE HAS DOUBLE MASTECTOMY IN CANCER SCARE DIAGNOSED WITH CANCER IN ONE BREAST Breast MRI: Friend or Foe? •Comments: 0 ASSOCIATED PRESS 8/19/2008 Applegate's cancer was detected early UCSF Postgraduate Course through a doctor- May 18, 2013 ordered MRI. She said she's starting a program to help Cheryl Ewing, MD women at high risk Clinical Professor of Surgery for breast cancer to meet the costs of an UCSF Department of Surgery MRI, which is not always covered by insurance. Breast MRI: background Breast MRI • First performed nearly 30 years ago � The breast is scanned in an MRI device before and as one of the first applications for after the intravascular injection of a contrast agent body MRI (Gadolinium DTPA). • Provides both spatial and temporal resolution � The pre-contrast images are "subtracted" from the – Morphology post-contrast images, and any areas that have – Kinetic characteristics increased blood flow are seen as bright spots • Advantages: (enhancements) on a dark background. – High sensitivity – Ability to detect occult cancers � Since breast cancers generally have an increased • Disadvantages blood supply, the contrast agent causes these lesions – Lower, more variable specificity to "light up” (enhance) on the images. – Overlap in the imaging of benign and malignant lesions 1

MRI, normal study Breast MRI Sagittal MIP (maximum intensity projection) Normal nipple enhancement Sensitivity and Specificity ACS Guidelines for Breast MRI disease • MRI screening recommended for: • Sensitivity: the probability that the test will be positive in someone with – Patients with known genetic mutation + - the disease ( “ PID: positive in disease ” ) – First-degree relative with known mutation a / (a + c) = a b – 20-25% lifetime risk of breast cancer + true false – History of chest wall radiation between ages 10 and 30 SnOUT=Sensitive tests, when test positives positives Negative, rule OUT disease – Two first degree relatives with breast cancer c d - • Specificity: the probability that the • NOT recommended for: false true test will be negative in someone negatives negatives – Personal history of breast cancer (unless ( “ NIH: negative in health ” ) who does not have the disease mammographically occult) d / (b + d) = – Mammographically dense breast tissue – ADH or LCIS SpPIN=Specific tests, when Positive, rule IN a disease – Average-risk women • Accuracy: (a + d) / (a + b + c + d) 2

Bilateral screening MRI MRI Screening Studies in high risk patient (BRCA-1) High Risk Women Axial MIP Study Year % Cancers Sensitivity (%) % Biopsies detected/#screened MMG U/S MRI recommended based on MRI Tilanus- 2000 2.8 0 -- 100 4.6 Linthorst, Netherlands Podo, Italy 2002 7.6 13 13 100 8.6 Morris, USA 2003 3.8 0 -- 100 16.1 Kriege, 2004 2.4 40 -- 71 2.9 Netherlands Warner, Canada 2004 9.3 36 33 77 15.7 Kuhl, Germany 2005 8.1 33 40 91 14.7 Lehman, USA 2005 1.1 25 -- 100 6.3 Leach, UK 2005 5.1 40 -- 77 -- Lehman, USA 2007 3.5 33 17 100 8.2 Sardanelli, Italy 2007 6.5 59 65 94 9.0 Right breast screening MRI Invasive lobular carcinoma (occult on PE, Occult Ipsilateral Cancer mammo) Early post Late post R breast MRI post Gd subtracted images 3

BIRAD 4 Dense Breast Breast MRI Dense Breast ACR recommendations: • Breast MRI for women with a breast cancer diagnosis for extent of disease and to rule occult disease in both breast • Not recommended for women with no risk factors. Impact of MRI on Ipsilateral Occult Contralateral Cancer Surgical Management Dense Breast Right ILC Left DCIS Study Year n % with additional ipsilateral disease Orel 1995 64 11 Fischer 1999 336 15 Tan 1999 83 6 Tillman 2002 207 9 Bedrosian 2003 267 18 Shelfout 2004 170 25 Berg 2004 111 26 TOTAL 1238 16 *BCT to wider excision or mastectomy 4

MRI-detected Contralateral Cancer in Breast MRI for Unknown Primary Patients with Diagnosis of Breast Cancer Study Year n % with additional contralateral • Rare; <1% of reported breast cancers disease • Outcome may be better than in those with known primary and axillary metastasis Rieber 1997 34 9 • Breast MRI identified the primary cancer in the breast Fischer 1999 463 3 Slanetz 2002 17 24 in 60% of cases Liberman 2003 223 5 • Has allowed breast conservation in patients Lee 2003 182 4 Viehweg 2004 119 3 presenting with unknown primary or Berg 204 111 3 • Radiation therapy alone if negative. Lehman 2005 103 4 Pediconi 2007 118 19 Lehman 2007 969 3 TOTAL 2339 4.4 MRI allows more accurate measure of response to neoadjuvant therapy C ALGB I NTER S PORE A CRIN N CICB Pre-chemotherapy Post-chemotherapy I nvestigation of S erial studies to P redict I SPY WITH MY Y our LITTLE T herapeutic EYE . . . . . . . A BIO- R esponse with MARKER BEGIN- I maging and ING WITH (AC, 4 cycles) X A nd . . . . mo L ecular analysis LD=47 mm LD=16 mm 5

MRI Reveals Several Phenotypes I SPY 1 TRIAL Design Neoadjuvant Chemotherapy Surgery 1 2 3 4 5 1: Single predominant mass with identifiable Serial Core Biopsies Outcomes rim, displacing Serial MR Imaging 2: Nodular pattern, irregular borders • Residual Disease 3: Diffuse infiltrative pattern • Recurrence 4: Patchy enhancement 5: Septal spread MRI assessment of letrozole Breast MRI for DCIS response in DCIS • ACRIN study 6667 (Lehman, NEJM 2007) baseline treated – Mammo occult contralateral breast cancer study- 969 women, 135 recommended for bx, 121 underwent sampling (needle bx or mastectomy) – 30 (3.1%) occult cancers diagnosed; 12 were DCIS • Prospective observational study (Kuhl, Lancet 2007) – 167 women diagnosed with DCIS (MMG and MRI) – Sensitivity of MMG compared to that of MRI: All DCIS High grade DCIS MMG 56% 52% Responder: ER-positive, postmenopausal MRI 92% 98% pathological CR 6

MRI assessment of letrozole MRI assessment of letrozole response response baseline treated baseline treated Responder: ER-positive Mixed Responder: ER-positive postmenopausal postmenopausal CALGB Proposal: Single Arm Phase II CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS Trial of Neoadjuvant letrozole for DCIS primary study endpoints : 3-month and 6-month radiographic • Inclusion criteria: response of MRI-measured tumor volume •Postmenopausal • V3 : defined as the difference in tumor volume between •Pure ER and/or PR (+) 6-months baseline (pre-treatment) and 3-month MRI DCIS on core biopsy • V6 : defined as the difference in tumor volume between •DCIS visible on MRI •Non high-grade baseline and 6-month MRI disease primary measurements: • Exclusion criteria: • Mean of V3 for all patients •Suspicion of invasive MMG MMG MMG • Mean of V6 for all patients cancer on core biopsy MRI MRI MRI or MRI Surgery (only if Surgery core bx •Palpable DCIS progression) •Extent >5 cm •Current exogenous hormone use 7

CALGB Proposal: Single Arm Phase II Summary Trial of Neoadjuvant letrozole for DCIS Secondary study endpoints: • • Recommended for: • MMG change with treatment – Screening patients at high risk • Lumpectomy rate – Evaluation of extent of disease in newly diagnosed • Margin status (pos/neg, margin breast cancer size) – Monitoring treatment response in neoadjuvant setting • Prevalence of invasive cancer – Work up of patients with unknown primary • Prevalence of pathologic CR – Planning size of lumpectomy to improve margin status • Treatment-related adverse events • Consideration of potential benefits and harms important to appropriate use of this technology. Stress and unnecessary biopsies/mastectomies. BRCA2 -Associated Cancers: BRCA1 -Associated Cancers: Lifetime Risk Lifetime Risk Breast Cancer 85% breast cancer Male Second Primary Breast (56% − 85%) Breast Cancer male breast cancer Cancer 3% per year ?% (6-8%) Ovarian Cancer ovarian cancer 30-54% Prostate (20% − 30%) Cancer 30 to 50% 8