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Acknowledgements Radiology • Scott Graham Breast Cancer Advocates • Nola Hylton • Chloee Wendorf • Susie Brain • Dian Heditsian • Bonnie Joe • Michael White • MRI and PET Imaging Markers For Kim Ray • Jim Slater Funding Support • Deep Hathi • Salma Javin • Mt. Zion Health Fund Prediction of Treatment Response in • Margarita Watkins • Henry VanBrocklin • Breast Oncology Program • Wen Li Breast Care Center • Breast Cancer Patients • David Newitt Give Breast Cancer a Boot • Laura Esserman • Youngho Seo • Susan G. Komen SAC110017 Ella F. Jones, PhD • Rita Mukhtar • Ben Franc • NIH/NCI U01CA151235 [email protected] • Jo Chien • Rob Flavell • NIH/NCI P01CA210961 • Ruby Gao 4/20/2021 • Miguel Pampaloni • NIH/NCI R01CA227763 • Julissa Melina‐Vega • Courtney Lawhn‐Heath • DOD W81XWH‐18‐1‐0671 Breast cancer patients and their families 4/20/2021 2 Learning objectives Neoadjuvant chemotherapy (NAC) in breast cancer National Surgical Adjuvant Breast and Bowel Project (NSABP): protocol B‐18 and B‐27 . How imaging markers are used in the neoadjuvant treatment trial . No difference in disease‐free survival or overall survival in patients . MRI markers for the prediction to treatment response and recurrence receiving neoadjuvant chemotherapy with AC or AC + taxane compared to free survival those receiving adjuvant therapy . Use of PET molecular imaging markers to inform assess early treatment . Opportunities Clinical Trial Model response and drug selection • Assess the intact primary tumor and refine treatment • Understand tumor biology in responseAdjuvant to treatment Neoadjuvant • DevelopEndpoint new tools for prognosticSurvival assessment Primary tumor • Accelerate new drug development response Timeline Years (5‐20) Months Rastogi et al., JCO, 2008 3 4 1 4/20/2021 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] Contrast‐enhanced MR Imaging I‐SPY 1/ACRIN 6657 PI: Esserman and Hylton Pre‐contrast (t ) t Functional tumor volume 0 1 t2 . Functional tumor volume (FTV) has been used to pCR and RCB monitor treatment response in breast cancer patients Anthracycline (AC) Taxane (T) . Using a three‐time point acquisition strategy (t0,t1 MR1 MR2 MR3 MR4 and t2) at the time of contrast injection, a signal‐ enhancement‐ratio (SER) map is generated . FTV is the sum of all the voxels meeting the FTV1 FTV2 FTV3 FTV4 enhancement threshold in the SER map pCR = pathologic complete response RCB = residual cancer burden Hylton, Magn Reson Imaging Clin N Am. 1999 Hylton et al., Radiology, 2012 5 6 I‐SPY 1/ACRIN 6657 Key Findings I‐SPY 2 TRIAL PI: Esserman & Berry . MRI volume (FTV) was a strong Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And MoLecular Analysis predictor of pCR and RCB at all FTV2 time point • I‐SPY 2 is a response‐ adaptive phase II trial testing . FTV was a stronger predictor of novel agents for breast recurrence free survival (RFS) cancer than pCR • Drugs “graduate” from I‐SPY 2 when they reach a . FTV2 had the highest overall C Bayesian predictive statistic when combined with probability of achieving 85% RCB success in a subsequent 300‐ patient phase III trial . FTV (highest quartile cut point) >3000 patients registered • MRI response is used to discriminate differences in >1500 patients completed surgery adjust patient randomization 14 agent combinations completed survival outcomes and the ratio and to estimate the 7 drug graduated FTV4 predictive probabilities optimal timing of MR imaging Hylton et al., Radiology, 2012 measurement differ by subtype Hylton et al., Radiology, 2016 7 8 2 4/20/2021 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] Forego chemo for Dedicated breast PET (Db‐PET) I‐SPY 2.2 Schema excellent responders . Imaging of the primary breast tumor during treatment can provide critical prognostic and predictive Randomization Surgery information . High sensitivity of dbPET can detects tumors at low dose of radiotracers (൑5 mCi) allowing longitudinal studies with minimum radiation exposure . A 39-year-oldHigh‐resolution breast imaging capability from dedicated breast PET, we will be able to captureDbPET early treatment was cancerresponse patient as well with as high quality imaging features that are of prognostic value able to resolve an agglomerate of the agglomerate Pre‐NAC (T0) Early‐NAC (T1)Mid‐NAC (T2) Post‐NAC (T3) ER+/PR+/HER2+ highlighting the tumors imaged by multifocality and 18 [ F]FDG-wbPET at heterogeneity of dbPET dbPET Randomize to targeted treatment the pre-treatment the primary for poor responders timepoint. tumor. 9 wbPET dbPET 10 Initial experience with FDG‐dbPET Initial experience with dbPET . Patient characteristics 32 yo female BRCA 1 carrier with a 2 lesions in the right and 1 in the left • 32 yo female BRCA 1 carrier with 3 biopsy confirmed lesions TN . 2 lesions in the right breast SUVmax • ER+/PR‐, HER2‐ Overall FTV TN: 19.5 73.2 cc ER+: 19.1 • Triple negative (TN) ER+ . 1 lesion in the left breast • Triple negative (TN) Overall FTV SUVmax . A dose of 5 mCi of FDG was administered and the patients was imaged in 89.5 cc TN: 15.3 the prone position at 45 min post‐injection MRI examinations at later time points showed a more dramatic response to therapy in the TN tumor and near complete 11 12pathologic response was documented at mastectomy Jones et al., Clinical Breast Cancer, 2017 3 4/20/2021 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] Results Early detection of treatment response dbPET DCE‐MRI Patient Characteristics 3 weeks of Tx 3 weeks of Tx 100 100 Pre‐treatment 30 30 Age 42.5 ABC mean (range) (29‐63) Subtype HR+/HER2‐ 4 _T0 _T1 HR+/HER2+ 2 Responder SUVmax SUVmax HR‐/HER2+ 1 %Chg MTV0_1 %Chg SUVmax0_1 TN 5 D E F Ki67 47.8 0 0 ‐100 -100 mean (range) (17.5‐80.0) ≤1 >1 ≤1 >1 ≤1 >1 ≤1 >1 RCB RCB RCB≤1 (pCR) 7 RCB RCB responder ‐ RCB>1 (non‐pCR) 3 Non 13 14 FES for imaging ER+ breast cancers Whole body FES‐PET of ER+ breast cancers ~70% breast cancers are ER+ 18F-FES PET imaging of 33 patients to evaluate • Equivocal lesions FDA APPROVED • ER status in metastatic disease Estradiol [18F]Fluoroestradiol • Origin of metastases A form of estrogen (FES) • 18F-FES PET improved diagnostic understanding in 88% of the patients and • FES was developed for PET imaging of ER status led to therapy change in 48% of the patients • Earlier clinical studies show that FES uptake in tumor correlates with the level of ER expression in biopsy samples and is predictive to endocrine treatment response Bone scan FES‐PET • These initial findings substantiate the utility of FES‐PET as an in vivo assay to select appropriate treatment for ER+ patients 15 16 Minturn et al., Radiology, 1988 Kruchten et. al JNM, 2012 4 4/20/2021 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] FES‐PET Imaging of ER+ Breast Cancer Initial experience of FES‐dbPET imaging Response to tamoxifen, fulvestrant, aromatase inhibitor (AI) . Patients with biopsy confirmed ER+ (>90%) and HER2‐ breast cancers were imaged with dbPET and standard breast dynamic contrast‐ enhanced magnetic resonance imaging (DCE‐MRI) . A dose of 5 mCi of FES was administered and patients were imaged in the prone position at 45 min post‐injection Linden et. al Clin. Cancer Res., 2011 Jones et al., NPJ Breast Cancer, 2019 17 18 Results Pre‐treatment ILC Pre‐treatment IDC FES‐dbPET Imaging of patients >90% ER+ . Todate,wehaveimaged DCE‐MRI FES‐dbPET DCE‐MRI FES‐dbPET 14 breast cancer patients with >90% ER+ and HER2‐ using [18F]FES‐dbPET ACABB Patient A Patient C . Patient age ranged from 23 to 76, with a range of Ki67 from 1 to 30% Patient D . While all patients have Patient B >90% ER+, they exhibit Patient C: Well circumscribed Diffused FES uptake pattern in ILCs different imaging pattern pattern in IDC Patient D: No FES uptake due to SUVmax = 15.83 SUVmax = 5.02 prior treatment with tamoxifen 19 20 5 4/20/2021 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS] FES‐dbPET Imaging of Response Summary Patient #1 . MRI FTV is a reliable marker to monitor neoadjuvant treatment response A B C . The use of FDG‐dbPET along with breast MRI may present an opportunity to guide earlier treatment redirection . FES‐dbPET has varying FES uptake pattern in ILC and IDC ER+ breast cancer diseases . SUVmax = 15.83 SUVmax = 6.11 Baseline FES‐uptake may inform treatment planning for ER+ breast cancer. Treatment induced change of FES‐uptake can be used to inform response and Patient #2 F subsequent treatment DEF 21 SUVmax = 35.24 SUVmax = 6.35 22 Future directions . In addition to FTV, MRI background parenchymal enhancement and apparent THANK YOU diffusion coefficient from diffusion weighted imaging are currently being explored as multivariate predictors . Compare FDG‐dbPET with MRI for assessing the early detection of treatment response . FES uptake to inform treatment selection in ER+ breast cancers. FES‐dbPET will also be used assess the efficacy of new selective ER degrader (SERD) Montgomery Street . Invasive lobular carcinoma is mostly ER+, we believe that FES‐dbPET uptake will provide important information of this breast cancer subtype . The high spatial resolution of dbPET and MRI may afford high quality radiomic features to correlate with molecular signatures to inform tumor biology Women’s Imaging Center 23 6 4/20/2021 [ADD PRESENTATION TITLE: INSERT TAB > HEADER & FOOTER > NOTES AND HANDOUTS].
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  • Onsite Program | 1 Welcome to the 2019 SBI/ACR Breast Imaging Symposium

    Onsite Program | 1 Welcome to the 2019 SBI/ACR Breast Imaging Symposium

    Connect to the Mobile App NOTE TAKING & BOOKMARKING Annotate directly on presentation slides and bookmark specific slides to view at a later time. CREATE & SHARE SCHEDULES Attendees can schedule sessions and personal items, then sync with their own calendars! PERSONAL SUMMARY Notes and bookmarked slides can be viewed, exported as PDFs, or printed at any time. SOCIAL FEATURES Attendees can view and communicate with other app users, speakers, and exhibitors. 1. Download the SBI Meetings App • Search for “SBI Meetings” in the Apple App Store or Google Play Store. • INSTALL and OPEN the app then SELECT the event: “2019 SBI/ACR Breast Imaging Symposium” • CLICK the icon to launch your app. 2. Login to your event App To start using your event app, select “Create Account” and type your name and email address. If you already have an account, select “Login” and enter your username (your email) and password. 3. Take notes on presentation slides Find the presentation you need and interact with the presentation by drawing on slides or highlighting text. Use the note-taking mode to type your notes next to each slide. Access your notes and print them out by clicking the “My Notes” on the home screen or “Online Personal Summary” in the hamburger menu. No mobile device? No Problem. As long as you have an internet connection, you can take notes on presentations through your laptop via this link: http://bit.ly/SBIACR19 Welcome to the 2019 SBI/ACR Breast Imaging Symposium Welcome to the 2019 SBI/ACR Breast Imaging At the conclusion Symposium, the largest breast imaging conference in of the symposium, the world! This conference is designed to bring together attendees should be the best speakers presenting the most up-to-date able to: information about the most important breast imaging topics.