Understanding and predicting fatigue, cardiovascular (CV) decline & events after breast cancer treatment (UPBEAT): A prospective multi-center wake forest NCORP research-base study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS602-TPS602
Author(s):  
Susan Faye Dent ◽  
Kerryn Reding ◽  
Glenn Jay Lesser ◽  
Heidi D. Klepin ◽  
Lynne I. Wagner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Time Course ◽  
Early Stage ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Exercise Intolerance

TPS602 Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients, treated with modern anticancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and the future development of CV events. The comprehensive assessment includes: ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, expanded short physical performance battery), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO2 peak via cardiopulmonary exercise test), and fatigue (via FACT-F). Eligibility criteria: age > 18 years; ECOG 0-2, able to walk without symptoms; receiving chemotherapy +/- HER2 targeted agent(s). To date, 244 participants are enrolled through 12 NCORP or ECOG-ACRIN sites. An additional 7 sites are onboarding and will be enrolling later in the year. Participants will be followed for 9 years with active surveillance of CV events (i.e., heart failure, myocardial infarction, stroke, all-cause and CV death). EA NCORP Grant: 2 UG1 CA189828 06; Research Base Grant: 2UG1 CA189824; R01: 1R01CA199167. Clinical trial information: NCT02791581 .

Understanding and predicting fatigue, cardiovascular (CV) decline, and events after breast cancer treatment (UPBEAT): A prospective cardio-oncology study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS11634-TPS11634
Author(s):  
Kerryn Reding ◽  
Ralph D'Agostino ◽  
Glenn Jay Lesser ◽  
Heidi D. Klepin ◽  
Lynne I. Wagner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Time Course ◽  
Early Stage ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Exercise Intolerance

TPS11634 Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients,treated with modern cancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and future development of CV events. The comprehensive assessment of factors includes ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, Expanded SPPB), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points, include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO2peak via cardiopulmonary exercise test), fatigue (via FACT-F). Eligibility criteria are: age >18 years; ECOG 0-2, able to walk without symptoms; and for BC patients, treatment with chemotherapy. 143 participants are accrued and currently enrolling through ECOG and NCORP sites. Participants will be followed for 9 years with active surveillance of CV events, i.e., heart failure, myocardial infarction, stroke, all-cause and CV death. Clinical trial information: NCT02791581.

scholarly journals Identification and Management of Lymphedema in Patients With Breast Cancer

2019 ◽  
Vol 15 (5) ◽  
pp. 255-262 ◽  
Author(s):  
Pavankumar Tandra ◽  
Avyakta Kallam ◽  
Jairam Krishnamurthy
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Treatment ◽  
Early Stage ◽  
Financial Burden ◽  
Breast Cancer Treatment ◽  
Initial Diagnosis ◽  
Axillary Surgery ◽  
Incidence Risk ◽  
End Stage

Breast cancer–related lymphedema (BCRL) is a potentially debilitating and often irreversible complication of breast cancer treatment. Risk of BCRL is proportional to the extent of axillary surgery and radiation. Other risk factors include obesity and infections. Given the 5-year survival rate of 90% and its potential impact on the quality of life of survivors of breast cancer, BCRL has become a significant financial burden on the health care system. Minimizing axillary surgery and radiation has been proven to reduce the risk of BCRL. Comprehensive multidisciplinary assessment at the time of initial diagnosis; early referral to physical therapy after surgery; and patient education regarding weight loss, skin, and nail care are cornerstones of the management of early-stage lymphedema. End-stage lymphedema may benefit from referral to a plastic surgeon specializing in lymphedema surgery. In this review, we attempt to review the incidence, risk factors, staging, prevention, and management of this complication of breast cancer treatment. We also describe our multidisciplinary approach for the prevention of this complication at the time of initial diagnosis.

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

2019 ◽  
Vol 26 (3) ◽  
Author(s):  
P. Kosalka ◽  
C. Johnson ◽  
M. Turek ◽  
J. Sulpher ◽  
A. Law ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Treatment ◽  
Growth Factor Receptor ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Obesity And Diabetes ◽  
Increased Risk ◽  
Symptomatic 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. 

scholarly journals Association between global longitudinal strain and cardiopulmonary fitness in patients with breast cancer

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Bonsignore ◽  
E Amir ◽  
T.H Marwick ◽  
B Thampinathan ◽  
C Brezden-Masley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Cardiac Risk ◽  
Left Ventricular ◽  
Funding Source ◽  
Cardiopulmonary Fitness ◽  
End Of Treatment

Abstract Background Anthracycline and trastuzumab therapies improve survival in the cancer population, but are limited by treatment induced cardiotoxicity. Echocardiography derived global longitudinal strain (GLS) permits more sensitive detection of cardiotoxicity than left ventricular ejection fraction (LVEF). However, the clinical implication of a reduction in GLS in cancer survivors is unknown. Purpose To define the association between GLS and cardiopulmonary fitness in women with breast cancer immediately post cancer therapy. Methods Women with HER2+ early stage breast cancer (EBC, Stage I-III) receiving anthracyclines followed by trastuzumab were recruited prospectively and followed between January 2015 and December 2019 with echocardiography during therapy. Left ventricular peak systolic GLS (GE EchoPAC, 3 apical views) and 3D-LVEF were measured prior to anthracyclines, and after completion of trastuzumab at 12 months. Exercise capacity was measured using a supine bicycle cardiopulmonary exercise test. Results of exercise testing at end of treatment were compared between patients with and without reduced GLS (absolute value ≤18% vs >18%) at the end of therapy. Results Amongst 128 women, 43 (34%) had a GLS ≤18% at the end of trastuzumab therapy. Baseline patient demographics including tumor characteristics and cardiac risk factors were similar between those with normal and abnormal GLS. During treatment 33 (25.8%) participants developed cardiotoxicity defined by the CREC criteria based on 3D-LVEF. Significant baseline (pre-cancer treatment) differences were found between groups for GLS (GLS 21.2±1.8 vs 19.6±2.2, p<0.001) and 3D LVEF (61.8±3.5 vs 60.2±3.7%, p=0.02) for those with GLS >18% and GLS ≤18% respectively at the completion of trastuzumab. Compared to those with GLS >18% those with GLS ≤18% had lower VO2peak (17.4±3.8 mL.kg-1.min-1 versus 20.2±4.9 mL.kg-1.min-1, p=0.001) despite similar effort (respiratory exchange ratio 1.14 versus 1.12, p=0.30). GLS following therapy (β coefficient: −0.596, SE 0.255; p=0.02) and age (β coefficient: −0.115, SE 0.057; p=0.047) were the only parameters associated with VO2peak after adjusting for relevant confounding factors. Conclusion A significant proportion of women receiving cancer therapy for HER2+ EBC had reduced GLS at end of treatment. Abnormal GLS at the end of cancer treatment was associated with lower VO2peak. Reduced VO2peak is strongly associated with late-occurring cardiovascular events and should prompt closer cardiac monitoring, cardiac risk factor management, and referral to exercise rehabilitation programs. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Canadian Institute of Health Research

scholarly journals Clinical and Sociodemographic Risk Factors Associated With the Development of Second Primary Cancers Among Postmenopausal Breast Cancer Survivors

2021 ◽  
Author(s):  
Stacyann Bailey ◽  
Charlotte Ezratty ◽  
Grace Mhango ◽  
Jenny Lin
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Treatment ◽  
Early Stage ◽  
Postmenopausal Breast Cancer ◽  
Second Primary ◽  
Study Cohort ◽  
Second Primary Cancers ◽  
Factors Associated ◽  
Increased Risk

Abstract Introduction: Advances in breast cancer (BC) diagnosis and treatment have increased the number of long-term survivors. Consequently, survivors of primary BC are at a greater risk of developing second primary cancers (SPCs). The risk factors for SPCs among BC survivors including sociodemographic, cancer treatment, comorbidities, and other medications have not been comprehensively examined. The purpose of this study is to assess the incidence and clinicopathologic factors associated with risk of SPCs. Methods: We analyzed 170, 639 women with early-stage primary BC diagnosed between January 2000-December 2015 from the Medicare-linked Surveillance Epidemiology and End Results (SEER-Medicare) database. SPC was defined as any diagnosis of malignancy occurring within the study period and at least two months after primary BC diagnosis. Univariate analyses compared baseline characteristics between those who developed a SPC and those who did not. We evaluated the cause-specific hazard of developing a SPC in the presence of death as a competing risk.Results: Of the study cohort, 20,838 (12%) of BC survivors developed a SPC and BC was the most common SPC type (32%). The median time to SPC was 42 months. Women who were white, older, and with fewer comorbidities were more likely to develop a SPC. While statins [hazard ratio (HR) 1.060 (1.016 - 1.106)] and anti-hypertensives [HR 1.517 (1.461 – 1.575)] increased the hazard of developing a SPC, aromatase inhibitor therapy [HR 0.588 (0.542 – 0.638)] and bisphosphonates [HR 0.897 (0.848 – 0.949)] were associated with a decreased hazard of developing any SPC, including non-breast SPCs.Conclusion: Our study shows that specific clinical factors including type of cancer treatment, medications, and comorbidities are associated with increased risk for the development of SPCs among older BC survivors. These results can increase patient and clinician awareness, target cancer screening among BC survivors, as well as developing risk-adapted management strategies.

Utilizing Cancer - Functional Gene Set - Compound Networks to Identify Putative Drugs for Breast Cancer

2018 ◽  
Vol 21 (2) ◽  
pp. 74-83
Author(s):  
Tzu-Hung Hsiao ◽  
Yu-Chiao Chiu ◽  
Yu-Heng Chen ◽  
Yu-Ching Hsu ◽  
Hung-I Harry Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cancer Survival ◽  
Expression Profiles ◽  
Functional Gene ◽  
Gene Set Enrichment Analysis ◽  
Gene Set ◽  
Gene Sets

Aim and Objective: The number of anticancer drugs available currently is limited, and some of them have low treatment response rates. Moreover, developing a new drug for cancer therapy is labor intensive and sometimes cost prohibitive. Therefore, “repositioning” of known cancer treatment compounds can speed up the development time and potentially increase the response rate of cancer therapy. This study proposes a systems biology method for identifying new compound candidates for cancer treatment in two separate procedures. Materials and Methods: First, a “gene set–compound” network was constructed by conducting gene set enrichment analysis on the expression profile of responses to a compound. Second, survival analyses were applied to gene expression profiles derived from four breast cancer patient cohorts to identify gene sets that are associated with cancer survival. A “cancer–functional gene set– compound” network was constructed, and candidate anticancer compounds were identified. Through the use of breast cancer as an example, 162 breast cancer survival-associated gene sets and 172 putative compounds were obtained. Results: We demonstrated how to utilize the clinical relevance of previous studies through gene sets and then connect it to candidate compounds by using gene expression data from the Connectivity Map. Specifically, we chose a gene set derived from a stem cell study to demonstrate its association with breast cancer prognosis and discussed six new compounds that can increase the expression of the gene set after the treatment. Conclusion: Our method can effectively identify compounds with a potential to be “repositioned” for cancer treatment according to their active mechanisms and their association with patients’ survival time.

scholarly journals Fabry Cardiomyopathy: Current Practice and Future Directions

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1532
Author(s):  
Jeffrey Yim ◽  
Olivia Yau ◽  
Darwin F. Yeung ◽  
Teresa S. M. Tsang
Keyword(s):  
Fabry Disease ◽  
Early Stage ◽  
Point Of Care ◽  
Left Ventricular ◽  
The Body ◽  
Cardiac Biomarkers ◽  
Dried Blood Spot ◽  
Point Of Care Ultrasound ◽  
Enzyme Replacement ◽  
Blood Spot

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficient galactosidase A enzyme and subsequent accumulation of glycosphingolipids throughout the body. The result is a multi-system disorder characterized by cutaneous, corneal, cardiac, renal, and neurological manifestations. Increased left ventricular wall thickness represents the predominant cardiac manifestation of FD. As the disease progresses, patients may develop arrhythmias, advanced conduction abnormalities, and heart failure. Cardiac biomarkers, point-of-care dried blood spot testing, and advanced imaging modalities including echocardiography with strain imaging and magnetic resonance imaging (MRI) with T1 mapping now allow us to detect Fabry cardiomyopathy much more effectively than in the past. While enzyme replacement therapy (ERT) has been the mainstay of treatment, several promising therapies are now in development, making early diagnosis of FD even more crucial. Ongoing initiatives involving artificial intelligence (AI)-empowered interpretation of echocardiographic images, point-of-care dried blood spot testing in the echocardiography laboratory, and widespread dissemination of point-of-care ultrasound devices to community practices to promote screening may lead to more timely diagnosis of FD. Fabry disease should no longer be considered a rare, untreatable disease, but one that can be effectively identified and treated at an early stage before the development of irreversible end-organ damage.

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