Anticancer Treatment of Breast Cancer Related to Cardiotoxicity and Dysfunctional Endothelium

Summary

Several cytotoxic regimens are related to endothelial cell damage and vascular toxicity. Endothelial dysfunction is implicated in the pathogenesis of all known cardiovascular diseases (CVD) and closely related to the metabolic syndrome. Both CVD and diabetes contributes importantly to total mortality and to breast cancer (BC) specific mortality.

In the epidemiological part of the project, the investigators will determine the prevalence and incidence of cardiovascular and metabolic morbidity/mortality in early BC patients compared to the Danish background population.

In the clinical part, the investigators will study the changes of endothelial function and metabolic parameters in BC patients receiving chemotherapy.

With increasing number of BC survivors, long-term consequences of curative cancer treatment should be studied. The investigators hypothesize that cytotoxic therapy worsens metabolic parameters possibly through endothelial dysfunction. If this is true, the next step will be to evaluate how strict metabolic control will affect prognosis.

Conditions

• Breast Neoplasms
• Endothelial Dysfunction
• Cardiovascular Disease
• Metabolic Syndrome

Interventions

PROCEDURE

Venous occlusion plethysmography

To characterize endothelial function in vivo the effect of vasodilatating substances is measured in the forearm circuit. The substances is administered via a thin catheter placed in the Brachial artery near the elbow in local anesthesia. Once the vessels dilate, the blood flow in the forearm will increase and the flow change is a measure of the vasodilatory capacity of that substance. The change is measured with classical venous occlusion plethysmography. The method described is established at Aarhus University Hospital and has been used for several decades to illustrate the effect of vasoactive drugs on the human circulation, meaning it is a proven and well documented method.

PROCEDURE

SphygmoCor

Applanation tonometry (pulse wave velocity and central blood pressure/arterial stiffness): The central blood pressure and the augmentation index is estimated from the shape of the radial pulse wave measured with a tonometer. Pulse wave velocity (PWV) is calculated from the average difference between the pulse pressure wave measured with a tonometer and the R in an ECG recorded simultaneously.

PROCEDURE

24hour blood pressure

24 hour blood pressure measurement

PROCEDURE

DEXA scan

Measurements of body composition: Total body fat and fat free mass is measured by Dual Energy X-ray Absorptiometry (DEXA).

BIOLOGICAL

Laboratory blood samples

Fasting blood tests are drawn from an antecubital placed catheter (albumin, ALAT/ASAT, alkaline phosphatase, bilirubin, gammaglutamyl transferase, coagulation factors, red and white blood cells, creatinin, potassium, sodium, fasting lipids, fasting glucose, hemoglobin A1C, insulin, sex hormones, von Willebrand factor, low grade inflammation markers, DNA and RNA for later analyses, including relevant coding genes). Further more urine samples to determine possible systemic impact of cardiovascular disease. We will create a biobank containing urine and blood samples from participants for future research, provided that the participant gives her permission. Responsibility for the biobank lies with the project responsible physician, Anders Bonde Jensen.

Sponsors & Collaborators

• Danish Cancer Society

  collaborator OTHER

• University of Aarhus

  lead OTHER

Principal Investigators

• Anders B. Jensen, Professor · Aarhus University Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-09-30

Primary Completion

2018-06-30

Completion

2018-06-30

Countries

• Denmark

Study Locations