Breast MRI: Friend or Foe?

Transcription

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

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

3 Bilateral screening MRI high risk patient (BRCA-1) Axial MIP MRI Screening Studies in High Risk Women Study Year % Cancers Sensitivity (%) detected/#screened MMG U/S MRI % Biopsies recommended based on MRI Tilanus- Linthorst, Netherlands Podo, Italy Morris, USA Kriege, Netherlands Warner, Canada Kuhl, Germany Lehman, USA Leach, UK Lehman, USA Sardanelli, Italy Right breast screening MRI Invasive lobular carcinoma (occult on PE, mammo) Early post Late post Occult Ipsilateral Cancer R breast MRI post Gd subtracted images 3

4 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 Surgical Management Dense Breast Study Year n % with additional ipsilateral disease Right ILC Occult Contralateral Cancer Left DCIS Orel Fischer Tan Tillman Bedrosian Shelfout Berg TOTAL *BCT to wider excision or mastectomy 4

5 MRI-detected Contralateral Cancer in Patients with Diagnosis of Breast Cancer Breast MRI for Unknown Primary Study Year n % with additional contralateral disease Rieber Fischer Slanetz Liberman Lee Viehweg Berg Lehman Pediconi Lehman Rare; <1% of reported breast cancers Outcome may be better than in those with known primary and axillary metastasis Breast MRI identified the primary cancer in the breast in 60% of cases Has allowed breast conservation in patients presenting with unknown primary or Radiation therapy alone if negative. TOTAL MRI allows more accurate measure of response to neoadjuvant therapy Pre-chemotherapy LD=47 mm Post-chemotherapy (AC, 4 cycles) LD=16 mm CALGB INTERSPORE ACRIN NCICB Investigation of Serial studies to Predict Your Therapeutic Response with Imaging and And molecular analysis I SPY WITH MY LITTLE EYE..... MARKER.. A BIO- BEGIN- ING WITH X.... 5

6 MRI Reveals Several Phenotypes I SPY 1 TRIAL Design Neoadjuvant Chemotherapy Serial Core Biopsies Serial MR Imaging Surgery Outcomes Residual Disease Recurrence : Single predominant mass with identifiable rim, displacing 2: Nodular pattern, irregular borders 3: Diffuse infiltrative pattern 4: Patchy enhancement 5: Septal spread Breast MRI for DCIS MRI assessment of letrozole response in DCIS ACRIN study 6667 (Lehman, NEJM 2007) 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: baseline treated All DCIS High grade DCIS MMG MRI 56% 92% 52% 98% Responder: ER-positive, postmenopausal pathological CR 6

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

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

9 Breast Cancer Risk Terminology BRCA Reports (Myriad) Loss of Heterozygosity (LOH) the functional allele become non functional (environmental hit). Loss of tumor suppression. Deleterious Mutation- germline frame shift mutation in both allele. Impact on protein production for DNA repair. Varying penetrance. Variant of Unknown Significance (VUS) mutation identified but unknown if harmful. Variant favor polymorphism is variation believed to be harmless. Benign 33 polymorphism-no mutations 34 Breast Cancer Risk Special Risk for being a mutation carrier for the BRCA 1 and 2 gene. 1.Any women diagnosed with breast cancer under the age of 40 years or multifocal, bilateral breast cancer under the age of 60 years. 2.Any women under the age of 60 and triple Negative ER(-), PR(-), HER-2 (-). 3.Any women of Jewish Ancestry (Ashkenazi), Hispanic, Mediterranean, Norwegian diagnosed with breast cancer under the age of 60 years. 4.Breast cancer diagnosis and family history of breast and ovarian cancer including 2 nd degree relatives. 5.Recurrent breast cancer in women under the age of 60 years. Breast Cancer Risk Breast Cancer Risk Women with a strong family history for breast cancer ( 2 or more first degree relatives with breast). 1 first degree relative with bilateral breast cancer. 2. Women with a family history of premenopausal breast cancer and/or Ovarian cancer All men with a breast cancer diagnosis should be tested for the BRCA 1 and 2 gene. Special attention for TP53 mutation in melanoma families and colon carcinoma. Others to screen are Cowden s and Li Fraumeni families. Li-Fraumeni strong family history of Leukemia, brain cancer, sarcoma, skin cancers. Cowden s Disease (multiple hamatomas) multiple hamatomas on nose by age 20 and in nasal and oral mucosa. Lifetime risk for breast cancer is 81%. Other associated cancers are thyroid, renal, uterine. Benign disorders multinodular goiters and fibroadenomatosis. 9

10 Thank you 10