Expression of Drug Resistance Markers in Breast Carcinomas - Impact on Adjuvant and Induction Chemotherapy

Hertha Firnberg Position T 71 Drug Resistance Markers in Breast Carcinomas Gudrun POHL 29.06.1999 Chemotherapy plays a major role in the treatment of breast cancer. Adjuvant and palliative chemotherapies are well established and neoadjuvant chemotherapy is increasingly becoming important. Because not all patients respond to chemotherapy, predictive tests in order to select those patients who may benefit from chemotherapy are urgently needed. Drug resistance factors which affect response to chemotherapy might be suitable candidates for predictive markers. Several drug resistance mechanisms are present in primary breast carciomas, but little is known on the exact impact of these resistance mechanisms on the outcome of adjuvant chemotherapy and induction chemotherapy. The aim of the present research project is to assess three drug resistance factors (MDR1/P-gp, MRP, LRP) for their predictive value with regard to response of breast cancers to either adjuvant chemotherapy or induction chemotherapy. Frequency and intensity of expression of resistance factors in primary breast carcinomas prior to any treatment, expression of resistance markers in lymph node metastases as compared to primary tumors, and expression of resistance markers in tumor tissues obtained by surgery after induction chemotherapy will be determined on a large patient population. Correlations between expression of resistance factors and known prognostic factors (e.g. tumor size, lymph node metastases, distant metastases, estrogen and progesterone receptor) will be evaluated. The association between expression of resistance markers and response to induction chemotherapy will be studied in detail. The impact of expression of resistance markers on overall survival and disease-free survival in patients receiving adjuvant chemotherapy will also be studied in detail. The results of these studies will clarify the clinical relevance of drug resistance factors in breast carcinomas, and, in particular, might help to determine whether these factors are of predictive or prognostic significance. If so, these factors might help to select those patients who benefit from adjuvant or induction chemotherapy.