Olga Oikonomidou: Clinical Translational Research in Breast Cancer

Image

Breast cancer is the most common cancer in women worldwide with more that 1.1 million women diagnosed annually. The pre-operative setting (neo-adjuvant chemotherapy) could provide an opportunity to study the impact of systemic therapies on breast cancer biology. As a research tool neo-adjuvant chemotherapy is useful because of the availability of tumour response as an end point and the availability of tissue for biopsy and biomarker development.

It is impossible to identify early during treatment those patients whose tumours will respond and those who will gain no apparent benefit in that their cancer either does not reduce appreciably, or even increases in size. There is an urgent need to determine on an individual basis whether treatment is producing a worthwhile effect. Treatments are not without undue toxicity and continuing with a therapy that is not beneficial reduces the potential to introduce other treatments.

With the advent of gene expression profiling it is now possible to analyse thousands of genes using small tissue samples from patient’s tumours. The predictive value of tumour phenotypes incorporating thousands of genes offers a more comprehensive approach for predicting response and benefit to treatment compared to testing a single gene. Thus we hypothesize that comprehensive molecular profiling of clinical samples, both diagnostic and on treatment may reveal alterations that are associated with drug resistance, metastatic recurrence and disease progression. Therefore we will be able to better characterize those cancers that receive insufficient benefit from current therapies and predict which alternate therapies and drug combination strategies may cure those patients that do not respond to current therapies.

Also in recent years a wealth of information indicating the potential use of circulating DNA for cancer screening, prognosis and monitoring of the efficacy of anticancer therapies has emerged. Detecting cfDNA in plasma or serum could serve as a 'liquid biopsy', which would be useful for numerous diagnostic applications and would avoid the need for tumour tissue biopsies. Use of such a liquid biopsy delivers the possibility of taking repeated blood samples, consequently allowing the changes in cfDNA to be traced during the natural course of the disease or during cancer treatment. cfDNA yields are higher in patients with malignant lesions than in patients without cancer. The events that lead to the increase of cfDNA during cancer development and progression are still not well understood. Recent data has shown that analyses of circulating DNA allow the detection of tumour-related genetic alterations that are relevant to cancer development and progression. Dr Oikonomidou’s group is developing non-invasive analyses of breast cancer in order to identify potential therapeutic targets in cancer and identify early a patient’s response to treatment. 

Biography