03/14/2019. Scope of the Problem. Objectives
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1 Cardiac Consideration During and After Breast Cancer Treatment Indu G. Poornima M.D Division of Cardiology Scope of the Problem 1 in 8 women will develop breast cancer 3.3 million women are survivors CVD is the leading cause of death among hormonereceptor positive postmenopausal women and exceed cancer mortality Shared risk-factors for cancer and cardiovascular disease, chemotherapy, targeted and endocrine therapy and radiation, may directly or indirectly affect cardiac function and cardiovascular homeostasis during and after cancer treatment. Objectives Identification of patients at risk for cardiovascular adverse effects, while receiving treatment for breast cancer. Understanding the optimal cardiac surveillance techniques for patients undergoing treatment for breast cancer. Discuss the current strategies that can be employed prior to, during and after breast cancer treatment that can mitigate the cardiovascular adverse effects. 1
2 Goals of Cardiooncology Prevent and manage CVD, to facilitate the delivery of optimal oncology treatment to improve overall outcomes. Management of Cardiovascular Disease in Women With Breast Cancer, Volume: 139, Issue: 8, Pages: , DOI: ( /CIRCULATIONAHA Medical Oncology Approaches to Breast Cancer Treatment Chemotherapy and Targeted Therapy for Breast cancer: Anthracycline-based regimen: ddac-t, TAC, FEC Anthracycline+targeted HER2 therapy: ACTH, ACTHP, FEC-DH Non-anthracycline regiemn+targeted HER-2 therapy: TCH, TCHP, TH, THP Antibody-Drug conjugates-tdm1 LV dysfunction is the most common and significant CV adverse effect Medical Oncology approaches to Breast Cancer Treatment Endocrine therapy: SERM (Tamoxifen)- DVT Aromatase inhibitors (Arimidex)- Hyperlipidemia SERD (Falsodex)- No CV effect known CDK-4/6 inhibitors: Pablociclib, Ribociclib, Abemaciclib- Ribociclib associated with QT prolongation 2
3 Management of CV Risk and Complications in the Breast Cancer Treatment Continuum Minimizing Cardiac Risk Prior to Cancer Treatment Assess underlying cardiac risk factors and their optimal treatment Prior CAD or CHF HTN, Diabetes, obesity, smoking, hyperlipidemia (ASCVD score) Assess h/o prior cancer treatments Prior anthracycline use (?dose) Prior left sided radiation Assessment of Cardiac Risk Prior to Cancer Treatment: Imaging for Assessment of LVEF ERNA (MUGA) TTE (echo) MRI Availability Advantages Reproducible, ease of performance, quantitative Ease of performance, no radiation Disadvantages Radiation Inconsistency of image quality, subjective assessment of LVEF Reproducibility Cost Image quality, accuracy, reproducibility, no radiation Claustrophobia, devices 3
4 Monitoring for Anthracycline Use Normal EF Baseline (prior to 100 mg/m2) 2 nd study after 250 to 300 mg/m2 3 rd at mg/m2 Sequential studies prior to each additional dose EF 30-50% EF study prior to each dose EF < 30% - recommend against initiating Discontinue Doxorubicin for decrease in EF >10% or absolute < 30% Minimizing Cardiac Risk During Cancer Treatment Choose and modify chemotherapeutic regimens Choose and modify radiation strategies Use Cardioprotective Strategies 4
5 Trials of Cardioprotective Medications 5
6 Cardio-protective Interventions Cardio-protective Interventions Cardio-Protective Interventions Small single center trials Variable endpoints Duration of treatment variable Summary- Aggressive treatment of cardiovascular risk factors and use of studied cardioprotective strategies if LVEF drops- Carvedilol, Lisinopril, Candesartan 6
7 Is LVEF the Best Measure of LV Systolic Dysfunction? Global Longitudinal Strain by Speckle tracking echo Global Longitudinal Strain and Torsion by MRI Diastolic Parameters Biomarkers Troponin I and T probnp Global Longitudinal Strain by Transthoracic Echo-? Superior to LVEF Page 21 7
8 Strain Imaging Bland-Altman plots of EF and GLS-derived EF showing interobserver and intraobserver variabilities. Stanton Page T 23 et al. Circ Cardiovasc Imaging. 2009;2: Page 24 8
9 Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy J Am Coll Cardiol. 2000;36(2): doi: /s (00) Left ventricular ejection fraction (LVEF) at baseline and during the seven months of follow-up of troponin I positive (ctni+; solid circle) and negative (ctni ; solid square) patients. p < vs. baseline (month 0); p < vs. ctni group. Data are shown as mean ± 95% confidence interval. Page 25 Page 26 Serum Troponin T Levels after Treatment with Doxorubicin in Children with ALL Lipshultz S E et al. JCO 2012;30: Page 27 9
10 Page 28 Page 29 10
11 Surveillance After Completion of Cancer Treatment 90% 5-year survival rate for breast cancer leads to a large population of survivors Late onset cardiomyopathy reported with anthracycline and HER-2 antagonist use ASCO and NCCN guidelines recommend one echo in those with >2 cardiovascular risk factors and prior anthracycline use about 3-5 year F/U. Radiation related complications rare with contemporary doses but still likely in those with repeated treatments Cardiac Effects of Radiation Treatments Heart dose >4Gy associated with excess cardiac mortality of Darby SC; NEJM 2013 Linear increase in relative risk of major coronary events of 7.4% per Gray (Gy) increase in mean heart dose, without any threshold safe dose in which no events were observed -Taylor C; J Clin Oncol 2017 Noninvasive imaging in Detection of Radiation Associated Cardiovascular Disease 11
12 Case 1 52-year-old postmenopausal black woman:left breast invasive ductal carcinoma: clinical stage IIIA T2N2, ER-, PR-, HER2- HTN on 2 medications, obesity (BMI 36), sedentary lifestyle, no cardiac symptoms Exam:BP 150/90; Lipids: LDL 148, HDL 38, Triglycerides 168 Cancer Management: Neoadjuvant dose-dense dd-ac-t. followed by lumpectomy if surgically feasible and axillary lymph node dissection. Adjuvant left-sided whole breast and regional lymph node irradiation Cardiovascular Assessment and Management: Echocardiogram at baseline with myocardial strain Treatment of cardiovascular risk factors with BP control (ARB and beta blocker preferred) and cholesterol treatment during and after treatment Exercise program, nutrition counseling Echocardiogram within 1 y after completion of cancer treatment Case 2 41-year-old premenopausal white woman Right breast invasive ductal carcinoma: clinical stage IA T1c N0, ER+/PR+, HER2+ History of postpartum cardiomyopathy with HF at age 32 (LVEF 30%), Excellent functional capacity, no cardiac symptoms, On Carvedilol mg bid Recent Echo LVEF 45%, BP136/84, LDL 104, HDL 76, triglycerides 67 Cancer Management: Lumpectomy with sentinel lymph node biopsy, followed by Adjuvant paclitaxel and trastuzumab for 12 wk followed by trastuzumab for 1 year Right breast radiation, followed by Tamoxifen Cardiovascular Assessment and Management: Consider CMR for accurate LVEF assessment Continue HF therapy: increase carvedilol and add ARB, titrate as tolerated If LVEF on repeat imaging is less than 45%, discuss with the oncologist treatment choice weighing cardiac dysfunction and cancer risk. Establish a plan for follow-up LVEF assessment during treatment using echocardiogram with strain or CMR Baseline and on-treatment biomarkers based on symptoms Continue exercise, monitor symptoms 12
13 Case 3 43-year-old white female with BRCA1 germline deleterious mutation and history of Stage IIA T2N0 invasive left breast ductal carcinoma 3 at age 30, treated with lumpectomy and sentinel lymph node biopsy, ddac-t, postlumpectomy radiation. Echocardiogram in survivorship at 1 year showed mildly dilated LV, LVEF 45% (prior to treatment 60%) and moderate mitral regurgitation. Cardiovascular Assessment and Management: Evaluate other causes or contributing factors to cardiomyopathy including ischemia, infiltrative disease, myocarditis and hyperthyroidism CMR, CCTA, and laboratory assessment Initiate HF therapy with beta blockers, ACEinhibitors* Biomarkers such as NT-proBNP at baseline and subsequently to monitor volume status Establish a plan for following of LV function and mitral regurgitation Encourage exercise and refer to cardiac rehabilitation in patients who meet cardiac rehabilitation criteria) What Does a Dedicated Cardiooncologist Do? Assists the oncology team with a systematic approach to cardiovascular evaluation and management in patients undergoing cancer treatment Use patient-centered techniques for earlier detection of toxicity Be aware of the myriad of side effects from the different regimens including newer agents and drug interactions Maintain long-term cardiovascular health to prevent late sequelae Contribute to developing institutional guidelines for cardiac management in oncology patients. Unanswered Questions in Breast Cancer Cardiooncology 1. Cardiovascular prognosis in HER-2 positive metastatic breast cancer, on targeted therapy lifelong- SAFE-Heart 2. Role of strain measurement in initiating cardioprotective medications- SUCCOUR 3. Accurate Identification of patients at risk using genetic testing 4. Role of cardiac rehabilitation in mitigating adverse effects of cancer therapy. 13
14 Thank You! Page 40 14
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