Breast MRI: Friend or Foe?

Transcription

1 Breast : Friend or Foe? APPLEGATE HAS DOUBLE MASTECTOMY IN CANCER SCARE DIAGNOSED WITH CANCER IN ONE BREAST Comments: 0 ASSOCIATED PRESS 8/19/2008 UCSF Postgraduate Course March 19, 2009 E. Shelley Hwang MD, MPH Associate Professor UCSF Department of Surgery Applegate's cancer was detected early through a doctorordered. She said she's starting a program to help women at high risk for breast cancer to meet the costs of an, which is not always covered by insurance. Breast : background First performed nearly 30 years ago as one of the first applications for body 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 (low specificity) 1

2 A brief statistical digression ACS Guidelines for Breast Sensitivity: the probability that the test will be positive in someone with the a / (a + c) ( PID: positive in ) SnOUT=Sensitive tests, when Negative, rule OUT Specificity: the probability that the test will be negative in someone who does not have the d / (b + d) ( NIH: negative in health ) SpPIN=Specific tests, when Positive, rule IN a test a true positives c false negatives b false positives d true negatives 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 NOT recommended for: Personal history of breast cancer Mammographically dense breast tissue ADH or LCIS Average-risk women Accuracy: (a + d) / (a + b + c + d) Bilateral screening high risk patient (BRCA-1) Axial MIP 2

3 Right breast screening Invasive lobular carcinoma (occult on clinical examination, mammo) Early post Late post Screening Studies in High Risk Women Study Year % Cancers Sensitivity (%) detected/#screened MMG U/S % Biopsies recommended based on Tilanus- Linthorst, Netherlands Podo, Italy Morris, USA Kriege, Netherlands Warner, Canada Kuhl, Germany Lehman, USA Leach, UK Lehman, USA Sardanelli, Italy Occult Ipsilateral Cancer Impact of on Ipsilateral Surgical Management* Study Year n % with additional ipsilateral Orel Fischer Tan Tillman Bedrosian Shelfout Berg R breast post Gd subtracted images TOTAL *BCT to wider excision or mastectomy 3

4 Right ILC Occult Contralateral Cancer Left DCIS -detected Contralateral Cancer in Patients with Diagnosis of Breast Cancer Study Year n % with additional contralateral Rieber Fischer Slanetz Liberman Lee Viehweg Berg Lehman Pediconi Lehman TOTAL Breast for Unknown Primary Rare; <1% of reported breast cancers Outcome may be better than in those with known primary and axillary metastasis Breast identified the primary cancer in the breast in 60% of cases Has allowed breast conservation in patients presenting with unknown primary allows more accurate measure of response to neoadjuvant therapy Pre-chemotherapy Post-chemotherapy (AC, 4 cycles) LD=47 mm LD=16 mm 4

5 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 A BIO- MARKER BEGIN- ING WITH X.... I SPY 1 TRIAL Design Neoadjuvant Chemotherapy Serial Core Biopsies Serial MR Imaging Surgery Outcomes Residual Disease Recurrence I SPY 2 Protocol Breast for DCIS Her-2 (+) Her-2 (-) Bx Hormonal Rx Chemo Herceptin qweek x3 Hormone Rx Trial (ACOSOG) Bevacizumab 10mg/kg Day1 OpenTrial H+Chemo or Standard H+Chemo OpenTrial Bev+Chemo or DDAC Bev DDT Bev Surgery Targeted agent x 1 year ACRIN study 6667 (Lehman, NEJM 2007) Contralateral breast cancer study 30 occult cancers diagnosed; 12 were DCIS Prospective observational study (Kuhl, Lancet 2007) 167 women diagnosed with DCIS (MMG and ) Sensitivity of MMG compared to that of : MMG All DCIS 56% 92% High grade DCIS 52% 98% 5

6 assessment of letrozole response in DCIS assessment of letrozole response baseline treated baseline treated Responder: ER-positive, postmenopausal pathological CR Responder: ER-positive postmenopausal assessment of letrozole response CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS baseline treated 6-months Inclusion criteria: Postmenopausal Pure ER and/or PR (+) DCIS on core biopsy DCIS visible on Non high-grade Mixed Responder: ER-positive postmenopausal MMG core bx MMG Surgery (only if progression) MMG Surgery Exclusion criteria: Suspicion of invasive cancer on core biopsy or Palpable DCIS Extent >5 cm Current exogenous hormone use 6

7 contrast injection (gradual) (stabilized) (washout) CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS Serial DCIS tumor volumes decrease with neoadjuvant AI treatment primary study endpoints: 3-month and 6-month radiographic response of -measured tumor volume V3: defined as the difference in tumor volume between baseline (pre-treatment) and 3-month V6: defined as the difference in tumor volume between baseline and 6-month Post contrast slice baseline volume=3.125 cc 3-month volume=1.631 cc 6-month volume=0.990 cc primary measurements: Mean of V3 for all patients Mean of V6 for all patients Simple linear regression of V6 on V3 S 0 SI S 1 t 0 = 0 t 1 = 2.7 t2= 8.1 Signal Enhancement Ratio (SER) as a measure of lesion enhancement characteristics. The total volume of lesion enhancement is calculated for 4 thresholds of SER value ranges. The total tumor volume (volser) is computed by calculating the total volume of pixels with SER>1.0 S2 SER = 1 SER > 1 TIME (min) SER < 1 Corresponding slice from SER map CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS CALGB Proposal: Single Arm Phase II Trial of Neoadjuvant letrozole for DCIS 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 Change in biomarkers as a surrogate of drug effect Accrual considerations Accrual goal: 96 subjects/3 years Limited access trial in which five CALGB institutions are expected to participate Projected annual accrual: 8 patients per site Dropout rate: 10% due to non-visualization of tumor on Therefore, the expected annual accrual rate is 7 patients with assessable tumors per site, for an annual total of 35 7

8 Summary Recommended for: Screening patients at high risk Work up of patients with unknown primary Evaluation of extent of in newly diagnosed breast cancer Monitoring treatment response in neoadjuvant setting (invasive cancer, DCIS) Consideration of potential benefits and harms important to appropriate use of this technology 8