Sequential assessment of multidrug resistance phenotype and measurement of S-phase fraction as predictive markers of breast cancer response to neoadjuvant chemotherapy.
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.
Chevillard
S
S
Département de Transfert, Institut Curie, Paris, France.
Pouillart
P
P
Beldjord
C
C
Asselain
B
B
Beuzeboc
P
P
Magdelénat
H
H
Vielh
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001483:Base Sequence; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D017931:DNA Primers / Q000737:chemistry; D018432:Drug Resistance, Multiple; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics; D016196:S Phase
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D012334:RNA, Neoplasm