Prediction of response to docetaxel by quantitative analysis of class I and III beta-tubulin isotype mRNA expression in human breast cancers

Clin Cancer Res. 2003 Aug 1;9(8):2992-7.

Abstract

Purpose: The relationship of intratumoral mRNA levels of class I and III beta-tubulin isotypes with clinical response to docetaxel has been studied in breast cancer patients.

Experimental design: Expression of class I and class III beta-tubulin mRNA levels was determined by a real-time PCR in breast cancer tissues obtained from 39 patients with locally advanced breast cancers (n = 26) or locally recurrent breast cancers (n = 13) before docetaxel treatment.

Results: Class I beta-tubulin mRNA levels of responders [6.58 +/- 1.43 (x10(2)), mean +/- SE] were significantly (P = 0.002) lower than those of nonresponders [14.97 +/- 2.95 (x10(2))], and class III beta-tubulin mRNA levels of responders (1.38 +/- 0.40) were also significantly (P = 0.003) lower than those of nonresponders (7.43 +/- 2.77). Breast cancers were divided into four groups according to the expression status of class I and class III beta-tubulin isotype mRNA, i.e., the class I-high/class III-high group (n = 13), the class I-high/class III-low group (n = 7), the class I-low/class III-high group (n = 7), and the class I-low/class III-low group (n = 12). The class I-high/class III-high group showed a very low response rate (15%), whereas the class I-low/class III-low group showed a very high response rate (75%). The class I-high/class III-low group and the class I-low/class III-high group showed intermediate response rates of 57% and 43%, respectively.

Conclusions: These results demonstrate that high expression of class I and class III beta-tubulin isotype mRNA is significantly associated with docetaxel resistance, and determination of class I and class III beta-tubulin isotype mRNA levels would be useful in the prediction of response to docetaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Base Sequence
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • DNA Primers / chemistry
  • DNA, Complementary / metabolism
  • Docetaxel
  • Female
  • Humans
  • Middle Aged
  • Models, Genetic
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Postmenopause
  • Premenopause
  • RNA / metabolism
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Taxoids / therapeutic use*
  • Treatment Outcome
  • Tubulin / biosynthesis*

Substances

  • Antineoplastic Agents, Phytogenic
  • DNA Primers
  • DNA, Complementary
  • RNA, Messenger
  • Taxoids
  • Tubulin
  • Docetaxel
  • RNA