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Sequential assessment of multidrug resistance phenotype and measurement of S‐phase fraction as predictive markers of breast cancer response to neoadjuvant chemotherapy
Author(s) -
Chevillard Sylvie,
Pouillart Pierre,
Beldjord Chérif,
Asselain Bernard,
Beuzeboc Philippe,
Magdelénat Henri,
Vielh Philippe
Publication year - 1996
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19960115)77:2<292::aid-cncr11>3.0.co;2-x
Subject(s) - medicine , chemotherapy , breast cancer , multiple drug resistance , cancer , oncology , doxorubicin , phenotype , drug resistance , pathology , gene , biology , biochemistry , microbiology and biotechnology
BACKGROUND The authors examined the relevance of S‐phase fraction (SPF) and multidrug resistance (MDR) phenotype as predictive tests of breast cancer response in a series of patients treated by conventional doses of neoadjuvant chemotherapy with (FAC) or without (FTC) doxorubicin. METHODS Fine needle samplings of tumors were used to measure SPF by flow cytometry before treatment (Day 0), and to assess the MDR phenotype using semiquantified reverse transcriptase polymerase chain reaction and immunocytochemistry, before and after (Days 8 and 28) the first cycle of chemotherapy. RESULTS Measurement of SPF before treatment was significantly associated with clinical response, but sequential assessment of MDR phenotype identified three groups of tumors with distinct outcomes: (1) tumors with a positive and constant expression of MDR1, in which prediction of resistance was restricted to patients treated by FAC; (2) tumors without any detectable expression, in which resistance to FAC or FTC treatments was rarely observed; and (3) tumors with an early (Day 8) acquired or increased MDR1 gene expression, which were always resistant to therapy to both treatment regimens. These results were confirmed at the protein level. CONCLUSIONS Sequential assessment of MDR phenotype is a relevant tool for monitoring breast cancer response in neoadjuvant chemotherapy. Cancer 1996;77:292‐300.