SEQUENTIAL ASSESSMENT OF MULTIDRUG-RESISTANCE PHENOTYPE AND MEASUREMENT OF S-PHASE FRACTION AS PREDICTIVE MARKERS OF BREAST-CANCER RESPONSETO NEOADJUVANT CHEMOTHERAPY

BACKGROUND. The authors examined the relevance of S-phase fraction (SP F) and multidrug resistance (MDR) phenotype as predictive tests of bre ast cancer response in a series of patients treated by conventional do ses of neoadjuvant chemotherapy with (FAG) or without (FTC) doxorubici n. METHODS. Fine needle samplings of tumors were used to measure SPF b y now cytometry before treatment (Day 0), and to assess the MDR phenot ype using semiquantified reverse transcriptase polymerase chain reacti on and immunocytochemistry, before and after (Days 8 and 28) the first cycle of chemotherapy. RESULTS. Measurement of SPF before treatment w as significantly associated with clinical response, but sequential ass essment of MDR phenotype identified three groups of tumors with distin ct outcomes: (1) tumors with a positive and constant expression of MDR 1, in which prediction of resistance was restricted to patients treate d by FAG; (2) tumors without any detectable expression, in which resis tance to FAC or FTC treatments was rarely observed; and (3) tumors wit h an early (Day 8) acquired or increased MDR1 gene expression, which w ere always resistant to therapy to both treatment regimens. These resu lts were confirmed at the protein level. CONCLUSIONS. Sequential asses sment of MDR phenotype is a relevant tool for monitoring breast cancer response in neoadjuvant chemotherapy. Cancer 1996; 77:292-300. (C) 19 96 American Cancer Society.