Danish Centre for Translational Breast Cancer Research (DCTB)

• The Danish Cancer Society (Kræftens Bekæmpelse)
• The Danish State Hospital (Rigshospitalet)
• University of Aarhus (Aarhus Universitetshospital)
• University of Copenhagen, LIFE (Københavns Universitet)
• University of Southern Denmark (Syddansk Universitet)

The major cancer among women in the Western World

Breast cancer is the major cause of death from cancer among women in the Western World, and there is an alarming increase in the number of new cases diagnosed every year – in the past 40 years alone the number of cases has tripled.

According to official statistics (2000), the numbers of new cases and deaths from breast cancer in Denmark is 3800 and 1200, respectively, and it is believed that in 2005 more than 4200 Danish women will be diagnosed with the disease. This corresponds to one in every 9 women.

Thus, it is evident that there exists an urgent need to re-access the current interventional efforts against breast cancer and in this context to think far past the traditional way of looking at and handling this disease.

This is the concept behind the Danish Centre for Translational Breast Cancer Research (DCTB).

Mammography today

At present, routine mammography is the most widely used tool for the early detection of breast cancer, and public screening programs have reduced breast cancer-related mortality.

To be detected, however, the tumour must be at least a few millimetres in size, a situation that potentially influences the odds of survival and cure.

In addition, mammography misses about 10% of all patients, gives a number of false positives as well as false negatives, and is inadequate for detecting non-calcified, pre-malignant and non-invasive disease. Early detection increases survival rate and represents a first line of defence.

Selection criteria for treatment

Parameters such as axillary lymph node status, tumour size, histological malignancy grade and age, in combination with predictive factors such as estrogen and progesterone receptors, are currently used for selecting the appropriate systemic therapy.

Patients with primary breast cancer are offered a combination of treatment options such as surgery, often followed by adjuvant irradiation, chemotherapy, and/or endocrine therapy.

Early detection can improve survival

Approximately 60% of patients with lymph-node positive disease will experience a recurrence, and most of them will die from disseminated breast cancer.

For patients with lymph-node negative disease, the 5-year recurrence rate is approximately 25%, suggesting that the risk of relapse and mortality is closely related to the stage of the disease at the time of primary surgery.

Presumably then, the survival rate of breast cancer can be improved if the number of patients being diagnosed with early-stage disease, that is node-negative disease, is increased.

In this context it would be important to develop new diagnostic tools to detect breast cancer at a very early stage, as this will provide one way to minimize disease-related mortality.

A need for predictive indicators and signatures

Currently, adjuvant systemic therapy is offered to patients with different risks of recurrence and death, i.e. to a prognostically heterogeneous group that constitutes about 70% of all new breast cancer patients.

Although adjuvant systemic therapy has led to a major improvement of the prognosis of the breast cancer population, it also carries the significant adverse effect of over-treatment.

It is known that response to a specific treatment is related to specific characteristics of the tumour and therefore, there is an urgent need to develop predictive indicators or signatures in primary breast cancer in order to stratify patients for tailored treatment.

New technologies

Today, the completion of the human genome project as well as the explosion of new technologies within genomics, proteomics and functional genomics ('omic' technologies) have brought much expectation in clinical practice as these technologies promise to revolutionise the way in which cancer will be diagnosed, treated and managed in the n future.

Available technologies range from tools that allow the analysis of mutations at single gene loci, to high-throughput expression profiling technologies that scan the whole genome. The integrated output of these technologies will lead to a better understanding of cancer pathogenesis and to a more effective translation of basic discoveries into the clinic for the benefit of the patient.

The main challenge, however, is how best to apply these technologies to clinically relevant samples such as tissue biopsies and bio-fluids in a well defined pathological and clinical framework.

Multidisciplinary research

Being a patient oriented organisation, The Danish Cancer Society catalysed in 2002 the creation of a multidisciplinary research environment, The Danish Centre for Translational Breast Cancer Research (DCTB), to spearhead the fight on breast cancer.

DCTB brings together scientists working in various areas of pre-clinical cancer research (cell cycle control, invasion and microenvironmental alterations, apoptosis, cell signalling, and immunology) with clinicians (surgeons, oncologists), pathologists and epidemiologists in an integrated, mission-oriented discovery-driven translational research environment.

DCTB places the patient at the centre, and its ultimate goal is to improve survival and quality of life of breast cancer patients.

Cooperation to benefit the patient

The underlying concept behind the mission-oriented approach is the use of multiple experimental paradigms to the prospective analysis of clinically relevant fresh samples obtained from the same patient, along with the systematic integration of the biological and clinical data sets.

The Centre efforts are supported by the Danish Breast Cancer Cooperative Group (DBCG), a consortia that manages a world-class tumour repository bank containing frozen tissue samples and fluids from approx. 10.000 breast cancer patients with clinical follow-up of up to 10 years.

DCTB has the following objectives:

• The elucidation of biochemical pathways, the relation and interrelation of individual proteins and their involvement in one or more pathways /biological systems.
• Development of new molecular non-invasive diagnostics able to detect breast cancer in the very early stages.
• Development of improved methodology to determine the various stages of breast cancer and to predict the outcome.
• Make better use of existing medicines through more effective targeting of high cost therapeutics, i.e., molecular classification (signatures) to identify best responders to treatment.
• To aid the discovery of new targeted therapies that are tailored for individuals rather than entire populations.