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

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.

• Authors: Seiichi Hasegawa, Yasuo Miyoshi, Chiyomi Egawa, Makoto Ishitobi, Tetsuya Taguchi, Yasuhiro Tamaki, Morito Monden, Shinzaburo Noguchi
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 8 Pg. 2992-7 (Aug 01 2003) ISSN: 1078-0432 [Print] United States
• PMID: 12912947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Base Sequence
• Breast Neoplasms (drug therapy, 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)