1. Curing Cancer and Caring for the Heart: Advancing the Care of Our Patients
Bonnie Ky, MD, MSCE
Assistant Professor of Medicine and Epidemiology
Senior Scholar, Center for Epidemiology and Biostatistics
Director, Penn Cardio-Oncology Research Program
Director, Penn Center for Quantitative Echocardiography
Perelman School of Medicine at the University of Pennsylvania

2. Patient Presentation
The patient is a 58 year old female with Her2+ left sided breast cancer undergoing therapy with doxorubicin and cytoxan, followed by taxol and herceptin.
She has no past medical history and is not taking any medications.
Her family history is significant for cardiac disease in her father. Her social history is unremarkable.
Her baseline and post-doxorubicin echocardiograms demonstrate a normal heart function, as assessed by left ventricular ejection fraction.

3. Patient Presentation
After 4 cycles of taxol and herceptin, her echo reveals a significant decline in heart function.
She denies any symptoms, except for fatigue.
Her physical exam is also fairly unremarkable, except for a BP of 142/85.

4. She Asks… Why did this happen? Is it common?
Is there any way we could have known earlier – before treatment – that her heart was going to be damaged?
Could this have been prevented?
What will happen to heart?
How could this affect her children - is her daughter also at risk for cancer and heart disease?

5. CV Disease and Cancer are Two Leading Causes of Death in the US
Intersection between cardiovascular (CV) disease and cancer
Common biologic basis
Common risk factors
Necessary cancer therapies can also adversely affect the CV system
CV Disease
Cancer
Number of deaths
Year
Koene, et al. Circulation

6. Cancer Treatments Can Affect the Heart in Many Ways
Arrhythmia
(“Abnormal rhythm”)
Heart Failure/
Cardiac Dysfunction
(“Weak or stiff heart muscle”)
Atherosclerosis
(“Heart blockages”)
Hypertension
(“Stiff Arteries” or Blood Pressure Increases)

7. Cancer Patients and Survivors are at Increased CV Risk
Growing burden of CV disease in cancer patients
In survivors with prior CV disease, risk of CV mortality (16.9%) exceeds cancer (14.6%) at 10 years
N = 12,500
Doxorubicin
Herceptin
Doxorubicin & Herceptin
Other
None
Doxorubicin
Herceptin
Doxorubicin & Herceptin
Other
None
20.1
20.1
HF or Cardiomyopathy Incidence
12.1
12.1
4.3
4.3
Years
Aiello Bowles, et al. JNCI
Abdel-Qadir, et al. JAMA Cardiol

8. What are our Priorities in the Cardiovascular Care of Cancer Patients?
Prior to Cancer Therapy
During Cancer Therapy
After Cancer
Therapy
How can we prevent CV disease?
How can we identify high risk patients?
How can we protect the heart?

9. Penn Cardiotoxicity of Cancer Therapy Cohort (CCT) Study
Inclusion criteria: Breast cancer, receiving doxorubicin +/- trastuzumab
Current N = 462
Baseline months months months year years ••• 10 years
* Echocardiogram; Blood samples obtained at baseline, and standardized intervals
between echocardiograms, and annually
Narayan…Ky. JACC Imaging

10. Cardiotoxicity of Cancer Therapy (CCT) Study Objectives
To understand what is the epidemiology of CV disease (how many, who, when?)
To develop a “risk score” using state-of-the-art imaging, blood markers, genetics (to identify CV disease before overt symptoms)
To develop innovative strategies to protect the heart (and understand who will derive the most benefit)
To ensure our patients can successfully be treated for their cancer while protecting their heart (in the short and long-term)

11. Novel CV Imaging Techniques
Baseline
Shortening
Strain = L1-L0 L0

12. Modest, sustained changes with doxorubicin
Most pronounced changes in CV function (ejection fraction) with doxorubicin & trastuzumab
Modest, sustained changes with doxorubicin
Major driver of decline (and recovery) in cardiac function is blood pressure
N = 1,255 echocardiograms
Maximum follow-up time for this analyses = 3.5 years
Narayan…Ky. Circulation

13. Circumferential Strain, %
Ventricular-Arterial Coupling
Yes Cardiac Dysfunction
No Cardiac Dysfunction

14. Additional Discoveries: Blood Markers Can Predict Risk
IgE
IgE
IgE
Control
Control
Case
ImmunoglobulinE (IgE) levels at baseline and throughout therapy consistently higher in controls, 5 to 58-fold, as compared to cases

15. Penn Cardio-Oncology Collaborative & Multi-Disciplinary Research
Breast Cancer
Protection Strategies
Pediatrics (Sarcoma, Leukemia)
Lymphoma
Multiple Myeloma
Prostate Cancer
Radiation Therapy
Sunitinib Therapy
Develop Mouse Model
Genetics of CV Disease
Penn
Cardio-Oncology

16. Penn Cardio-Oncology Translational Center of Excellence
Launching a Cardio-Oncology Translational Center of Excellence in 2017 with support of the Abramson Cancer Center, Department of Medicine, and Cardiology
Goals:
Build a premier, multi-disciplinary cardio-oncology program at the forefront of basic, translational, and clinical research and care
Bring together scientists and clinicians across basic, translational and clinical science to catalyze and accelerate new discoveries
Paired with clinical mission of delivering state-of-the-art, evidence-based medicine to oncology patients and survivors regionally and nationally

17. THANK YOU