Susan Dent

Overview:

Medical Oncologist with a focus on breast cancer
Associate Director of Breast Cancer Clinical Research
Co-Director Duke Cardio-Oncology Program

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1990

McMaster University (Canada)

Internal Medicine

Royal College of Physicians (United Kingdom)

Medical Oncology

Royal College of Physicians (United Kingdom)

Grants:

CardiovAscular Risk profile and Treatment patterns in ER+HER2 - Advanced Breast Cancer: A retrospective cohort study (CAREB)

Administered By
Duke Cancer Institute
Awarded By
Novartis Pharmaceuticals Corporation
Role
Principal Investigator
Start Date
End Date

A PHASEIB/III STUDY OF IPATASERTIB PLUS PALBOCICLIB AND FULVESTRANT VERSUS PLACEBO PLUS PALBOCICLIB AND FULVESTRANT IN HORMONE RECEPTOR POSITIVE AND HER2 NEGATIVE LOCALLY ADVANCED UNRESECTABLE OR METASTATIC BREAST CANCER

Administered By
Duke Cancer Institute
Awarded By
F. Hoffmann-La Roche Ltd
Role
Principal Investigator
Start Date
End Date

Publications:

Cardiovascular Toxicity of Novel HER2-Targeted Therapies in the Treatment of Breast Cancer.

PURPOSE OF REVIEW: HER2-targeted therapies have led to improved clinical outcomes in early and advanced breast cancer (BC). We review the long-term cardiotoxicity of HER2-targeted therapy in early and advanced BC, our current knowledge of cardiotoxicity of novel HER2-targeted therapies, and propose a cardiac monitoring (CM) strategy for this population. RECENT FINDINGS: Long-term data from studies with HER2-targeted therapy in the adjuvant setting have failed to demonstrate an increase in cardiotoxicity over time, and rates of cardiotoxicity seen with novel HER2 agents remain low. Despite over a decade of experience with HER2-targeted therapy, CM in clinical practice is inconsistent in patients with early BC and almost non-existent in advanced BC. Long-term follow-up of clinical trials with HER2-targeted agents in early and advanced BC has failed to demonstrate increased rates of cardiotoxicity over time, attesting to the long-term safety of this class of drugs for the majority of patients, although the long-term cardiac safety of newer HER2 agents in the non-clinical trial setting is largely unknown. We propose CM incorporating clinical history, cardiac imaging, and biomarkers.
Authors
Dent, SF; Morse, A; Burnette, S; Guha, A; Moore, H
MLA Citation
Dent, Susan F., et al. “Cardiovascular Toxicity of Novel HER2-Targeted Therapies in the Treatment of Breast Cancer.Curr Oncol Rep, vol. 23, no. 11, Aug. 2021, p. 128. Pubmed, doi:10.1007/s11912-021-01114-x.
URI
https://scholars.duke.edu/individual/pub1495121
PMID
34453232
Source
pubmed
Published In
Current Oncology Reports
Volume
23
Published Date
Start Page
128
DOI
10.1007/s11912-021-01114-x

Recognition, Prevention, and Management of Arrhythmias and Autonomic Disorders in Cardio-Oncology: A Scientific Statement From the American Heart Association.

With the advent of novel cancer therapeutics and improved screening, more patients are surviving a cancer diagnosis or living longer with advanced disease. Many of these treatments have associated cardiovascular toxicities that can manifest in both an acute and a delayed fashion. Arrhythmias are an increasingly identified complication with unique management challenges in the cancer population. The purpose of this scientific statement is to summarize the current state of knowledge regarding arrhythmia identification and treatment in patients with cancer. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. Despite increased recognition, dedicated prospective studies evaluating true incidence are lacking. Moreover, few studies have addressed appropriate prevention and treatment strategies. As such, this scientific statement serves to mobilize the cardio-oncology, electrophysiology, and oncology communities to develop clinical and scientific collaborations that will improve the care of patients with cancer who have arrhythmias.
Authors
Fradley, MG; Beckie, TM; Brown, SA; Cheng, RK; Dent, SF; Nohria, A; Patton, KK; Singh, JP; Olshansky, B
MLA Citation
Fradley, Michael G., et al. “Recognition, Prevention, and Management of Arrhythmias and Autonomic Disorders in Cardio-Oncology: A Scientific Statement From the American Heart Association.Circulation, vol. 144, no. 3, July 2021, pp. e41–55. Pubmed, doi:10.1161/CIR.0000000000000986.
URI
https://scholars.duke.edu/individual/pub1490006
PMID
34134525
Source
pubmed
Published In
Circulation
Volume
144
Published Date
Start Page
e41
End Page
e55
DOI
10.1161/CIR.0000000000000986

Clinical experience of patients referred to a multidisciplinary cardio-oncology clinic: an observational cohort study.

Introduction: Cardiovascular disease is the 2nd leading cause of long-term morbidity and mortality in cancer survivors. Cardio-oncology clinics (cocs) have emerged to address the issue; however, there is a paucity of data about the demographics and clinical outcomes of patients seen in the coc setting. Methods: Cancer patients referred to The Ottawa Hospital coc were included in this retrospective observational study. Data collected were patient demographics, cancer type and stage, reason for referral, cardiac risk factors, cardiac assessments and treatment, and clinical outcomes. Results: Between 2008 and 2015, 779 patients (516 women, 66%; 263 men, 34%) were referred to the coc. Median age of the patients at cancer diagnosis was 60 years (range: 18-90 years). The most frequent reasons for referral were decreased left ventricular ejection fraction (33%), pre-chemotherapy assessment (14%), and arrhythmia (14%). Treatment with cardiac medication was given in 322 patients (41%), 181 (56%) of whom received more than 2 cardiac medications, with 57 (18%) receiving an angiotensin-converting enzyme inhibitor (acei), 46 (14%) receiving an acei and a beta-blocker, and 38 (12%) receiving a beta-blocker. Of 163 breast cancer patients, 129 (79%) were able to complete targeted therapy with coc co-management. Most of the 779 patients (n = 643, 83%) were alive at the time of the last data collection. Conclusions: This cohort study is one of the largest to report characteristics and clinical outcomes of patients referred to a coc. Collaboration between oncologists and cardiologists resulted in completion of cancer therapy in most patients. Ongoing analysis of referral patterns, management plans, and patient outcomes will help to guide the cardiac care of oncology patients, ultimately optimizing cancer and cardiac outcomes alike.
Authors
Kappel, C; Rushton, M; Johnson, C; Aseyev, O; Small, G; Law, A; Ivars, J; Dent, S
MLA Citation
Kappel, C., et al. “Clinical experience of patients referred to a multidisciplinary cardio-oncology clinic: an observational cohort study.Curr Oncol, vol. 26, no. 3, June 2019, pp. e322–27. Pubmed, doi:10.3747/co.26.4509.
URI
https://scholars.duke.edu/individual/pub1397863
PMID
31285675
Source
pubmed
Published In
Current Oncology (Toronto, Ont.)
Volume
26
Published Date
Start Page
e322
End Page
e327
DOI
10.3747/co.26.4509

Effect of obesity, dyslipidemia, and diabetes on trastuzumab-related cardiotoxicity in breast cancer.

Background: Clinical trials have demonstrated an increased risk of cardiotoxicity in patients with breast cancer (bca) receiving trastuzumab-based therapy. Diabetes, dyslipidemia, and obesity are known risk factors for cardiovascular disease. Studies have yielded conflicting results about whether those factors increase the risk of cardiotoxicity in patients with bca receiving trastuzumab. Methods: In this retrospective cohort study, data were collected for 243 patients with bca positive for her2 (the human epidermal growth factor receptor 2) who were receiving trastuzumab and who were referred to The Ottawa Hospital Cardio-oncology Referral Clinic between 2008 and 2013. The data collected included patient demographics, reason for referral, cardiac function, chemotherapy regimen (including anthracycline use), and 3 comorbidities (diabetes, dyslipidemia, obesity). Rates of symptomatic cancer treatment-related cardiac dysfunction (sctcd) and asymptomatic decline in left ventricular ejection fraction (adlvef) were calculated for patients with and without the comorbidities of interest. Results: Of the 243 identified patients, 104 had either diabetes, dyslipidemia, or obesity. In that population, the most likely reason for referral to the cardio-oncology clinic was adlvef. The combination of 2 or 3 comorbidities significantly increased the incidence of sctcd in our population, reaching a rate of 67% for patients with obesity and dyslipidemia [relative risk (rr): 2.2; p = 0.04], 69% for patients with obesity and diabetes (rr: 2.3; p = 0.02), and 72% for patients with all 3 risk factors (rr: 2.4; p = 0.08). Conclusions: The combination of 2 or 3 comorbidities significantly increases the incidence of symptomatic cancer treatment-related cardiotoxicity. Patients with bca experiencing cancer treatment-related cardiotoxicity who have a history of diabetes, dyslipidemia, and obesity might require more proactive strategies for prevention, detection, and treatment of cardiotoxicity while receiving trastuzumab-based treatment.
Authors
Kosalka, P; Johnson, C; Turek, M; Sulpher, J; Law, A; Botros, J; Dent, S; Aseyev, O
MLA Citation
Kosalka, P., et al. “Effect of obesity, dyslipidemia, and diabetes on trastuzumab-related cardiotoxicity in breast cancer.Curr Oncol, vol. 26, no. 3, June 2019, pp. e314–21. Pubmed, doi:10.3747/co.26.4823.
URI
https://scholars.duke.edu/individual/pub1397864
PMID
31285674
Source
pubmed
Published In
Current Oncology (Toronto, Ont.)
Volume
26
Published Date
Start Page
e314
End Page
e321
DOI
10.3747/co.26.4823

Anthracycline-induced cardiotoxicity in patients with early-stage breast cancer: the Canadian Cancer Trials Group (CCTG) MA.21 experience.

<h4>Purpose</h4>Anthracyclines are frequently used in adjuvant treatment for early-stage breast cancer (ESBC). The purpose of this study was to evaluate cardiotoxic effects in the first five years after treatment with different anthracycline-based regimens.<h4>Methods</h4>CCTG MA.21 (NCT000142) was a phase III trial in ESBC that compared cyclophosphamide (75 mg/m<sup>2</sup>) orally for 14 days, epirubicin (60 mg/m<sup>2</sup>) and fluorouracil, IV days one and eight (CEF) for six cycles; dose-dense epirubicin (120 mg/m<sup>2</sup>) and cyclophosphamide, IV every 2 weeks for six cycles with concurrent G-CSF then paclitaxel every 2 weeks for four cycles (ddEC/T); doxorubicin (60 mg/m<sup>2</sup>) and cyclophosphamide (600 mg/m<sup>2</sup>) every 3 weeks for four cycles then four cycles q3 weekly paclitaxel (175 mg/m<sup>2</sup>) (AC/T).<h4>Endpoints</h4>LVEF decline; LV function changes (heart failure), or Grade 3-4 cardiac ischemia/infarction. A competing risk analysis was performed with endpoints of cardiotoxicity or recurrence in first 5 years after completion of chemotherapy.<h4>Results</h4>2104 women were randomized. Compliance with cardiac LVEF assessments was 70% at 5 years in all arms. The 5-year cumulative risks of any cardiac event for CEF, ddECT, and AC/T were 22.3% (95%CI 18.9 to 25.7), 14.2% (95%CI 11.0 to 17.3), and 8.1% (95%CI 5.8 to 10.4), respectively, p < 0.0001. At 5 years, women in the ddEC/T and AC/T group had significantly lower risk of cardiotoxicity than those given CEF (HR 0.599 and 0.371, respectively). Most events were asymptomatic drop in LVEF.<h4>Conclusions</h4>Asymptomatic changes in LVEF accounted for most of the cardiotoxicity. The majority of cardiac events occurred in year one although occurrence of cardiotoxicity over time highlights the need for improved risk stratification to guide cardiac surveillance strategies.
Authors
Dent, SF; Botros, J; Rushton, M; Aseyev, O; Levine, MN; Parulekar, WR; O'Brien, P; Burnell, M; Pritchard, KI; Chen, BE; Shepherd, LE
MLA Citation
Dent, S. F., et al. “Anthracycline-induced cardiotoxicity in patients with early-stage breast cancer: the Canadian Cancer Trials Group (CCTG) MA.21 experience.Breast Cancer Research and Treatment, vol. 184, no. 3, Dec. 2020, pp. 733–41. Epmc, doi:10.1007/s10549-020-05887-w.
URI
https://scholars.duke.edu/individual/pub1460898
PMID
32940847
Source
epmc
Published In
Breast Cancer Research and Treatment
Volume
184
Published Date
Start Page
733
End Page
741
DOI
10.1007/s10549-020-05887-w