The impact of 18 weeks of chemotherapy-treatment with Taxotere/Adriamycin/Cyclophosphamide (TAC) on skeletal muscle composition of female breast cancer patients

Recent population demographics of the Netherlands show that an increasing
number of people are diagnosed with cancer each year. In 2007 86.800 people
were diagnosed with cancer, and this number is expected to increase to 123.000
in 2020. This progression is a result of the growing number of people aged 65
years and over, together with a general aging of the population. Fortunately,
during the past few decades, the detection and treatment of cancer has made
substantial progress, leading to improved survival. The 5-year survival in male
cancer patients has increased from 41% in 1993 to 54% in 2007, and similar
increases are reported for female patients. Consequently, by 2020 the number of
cancer survivors in the Netherlands will be ~666.000, which represents ~4% of
the entire population. As both the number of cancer survivors and the length of
their survival increases, long-term health issues related to cancer and its
treatment are becoming more important.
A very serious side effect of cancer and its treatment concerns cachexia.
Cancer cachexia is defined as a multifactorial syndrome characterized by an
ongoing loss of skeletal muscle mass (with or without loss of fat mass) that
cannot be fully reversed by conventional nutritional support and leads to
progressive functional impairment. It is associated with reduced physical
function, reduced tolerance to anticancer therapy, and reduced survival.
Furthermore, loss of skeletal muscle mass is accompanied by an increased risk
of developing chronic metabolic diseases like obesity and type 2 diabetes.
To counteract these catabolic effects of cancer and its treatment, it is
important to identify the specific changes that occur in skeletal muscle
composition and function during cancer treatment. Research on skeletal muscle
composition during cancer treatment is very limited. Previous studies have
shown that cancer patients have lower endurance capacity and muscle strength
compared with healthy controls, and that this is accompanied by a decrease in
muscle fiber size and an increase in intramyocellular lipid content. However,
in order to get more insight into the pathophysiology of cancer cachexia, it is
important to study the specific changes in skeletal muscle tissue of cancer
patients that occur during treatment, and moreover to investigate these changes
in much more detail than described previously.

The aim of this study is to define the specific changes in skeletal muscle
composition and function, systemic inflammation and nutritional intake and
physical activity levels, during cancer treatment. To investigate this, we will
include 13 female breast cancer patients and assess body composition, skeletal
muscle composition, strength, and endurance capacity before and after 18 weeks
of chemotherapy. In addition we will measure markers of metabolism and systemic
inflammation in venous blood samples and determine changes in nutritional
intake and physical activity with different questionnaires.

The study is designed as an observational trial, comparing skeletal muscle
characteristics, body composition, aerobic capacity, muscle strength, metabolic
and inflammatory profile, and physical activity, diet and quality of life in
patients with breast cancer before and immediately after 18 weeks of
chemotherapy-treatment. An overview of the study design is shown in Figure 1 at
page 8 of the research protocol. Patients will be selected for participation by
their surgeon and oncologist in the period between surgery and start of
chemotherapy-treatment (usually 4 weeks). After informed consent is obtained,
the baseline tests will be performed on 2 separate occasions. The first tests
(T1) will be conducted 2 weeks before the start of chemotherapy at Máxima
Medical Centre Veldhoven, consisting of measurements of body composition,
maximal cycling exercise with respiratory gas analysis, and a muscle strength
assessment. The second part of testing (T2) will be conducted 1 week later at
Máxima Medical Centre Veldhoven, and includes a muscle biopsy from the vastus
lateralis muscle, blood sampling from an antecubital vein, filling out the
questionnaires under supervision of the researcher, and a muscle strength
confirmation test. Questionnaires will be repeated by mail in the week before
the 4th chemotherapy session (Q). After 18 weeks of chemotherapy-treatment all
subjects will undergo the same tests again (T1 and T2) in weeks 19 and 20.

Time investment:
- 4 visits to the hospital for the first and seconds assessments (body
composition, DEXA scan, strength test, endurance test, venous blood sampling,
muscle biopsy, questionnaires) before and after chemotherapy: each visit will
last 3 hours
- questionnaires will be repeated after 9 weeks of chemotherapy: 30-60 min of
patients' time

Participation in this study will provide the patients with detailed information
about their body composition, and endurance- and strength capacity. We will
provide this information at the end of the study, since individual outcomes may
influence patients* behaviour regarding diet and exercise during the study.
Participation in this study has no major health risks. The endurance- and
strength testing may evoke some muscle discomfort. The venous blood sampling
and the muscle biopsy can result in a local haematoma, which will resolve
within a week.