Trial Information

Involvement of Endogenous Digitalis-like Compounds in Breast Cancer

To pursue this question about endogenous DLC metabolism in cancer patients we intend to
start with the measurement of DLC plasma levels in breast cancer patients at the time of
first diagnosis and compare them to women with benign breast disease as well as healthy
women.

Aim of the Study

- To evaluate the basal DLC plasma concentrations in cancer patients at the time of first
diagnosis and the function of the HPA axis, with focussing on breast cancer patients.

- To analyze a potential change of HPA function and, in parallel, DLC plasma
concentrations in the course of therapy, with special respect to treatment failure.

- To establish a potential correlation between DLC plasma concentrations and risk factors
in BC.

Patients and Methods

Patients:

I. 50 - (100) patients with breast cancer at the time of first diagnosis

II. 50 - (100) patients with a benign disease of the breast

III. 50 - (100) women undergoing plastic surgery of the breast

IV. 50 - (100) women who need no further exploration after visit in ambulance (=normal
population)

V. additionally a group of 25 - 50 students (age 20-40) will be analyzed in a pilot study

Methods:

Time-schedule for Group I (Group II. - IV. alike, according to disease and/or situation)

- Day of first presentation of the woman at the clinic

- Day of first diagnosis, i.e. biopsy/FNA

- Day of start of treatment: operation, chemo-/radiotherapy (tst = 0)

- Day + 30, + 60, + 90

- 6 month and 1 year after start of treatment

The Group V. (students) will be analyzed in a special schedule, preceding the study 1-2
months:

- 4 weeks before an important exam

- a day before the exam (-3 days)

- a day after the exam (+ 3 days)

- 2 weeks after the exam

- 6 weeks after the exam

Parameters

Biochemistry (Group I. - V.)

- Basal DLC plasma concentration

- Basal serum Cortisol concentration

- Basal plasma ATCH concentration

- Basal Aldosterone/Renin concentration

- Electrolytes (potassium, sodium, calcium, chloride)

Pathology/Immunohistochemistry (Group I. + II., when benign, including last 4 points)

- Tumor size

- lymph node status

- E/P receptors

- Grade

- HER2/neu

- Bcl-2

- Ki67

- p53

Radiology (Group I.)

If abdominal CT available measurement of size of the adrenal glands

Endocrinologic tests (Group I. - IV.)

- Dexamethasone-test (low dose):

- 2 mg Dexamethasone p.o. at 24:00

- measurement of Cortisol and DLC at 8:00 the next morning

- ACTH-test:

- basal plasma concentrations of Cortisol, DLC and ACTH

- administration of 250 µg ACTH (Synachten®) i.v.

- measurement of Cortisol and DLC after 30 min. and 60 min.

- Facultative: Metapyrone test

at following time intervals:

1. Dexamethasone-test

- around the time of first presentation (± 5 days)

- around the time of start of treatment (± 5 days); corresponding times for Group
II.- IV.

- Day + 30, +60, +90

- 6 month and a year after start of treatment

2. ACTH-test

- On the day of first presentation

- On the day of start of treatment; corresponding times for Group II.- IV.

- Day + 30, +60, +90

- 6 months and one year after start of treatment

Psychometric test for Stress Evaluation (Group I. - V.)

- at the day of first presentation (Students: in between the last 2 weeks before an exam)

- at the end of the study