Microtubule-Associated Parameters as Predictive Markers of Docetaxel Activity in Advanced Breast Cancer Patients: Results of a Pilot Study

Bernard-Marty, Chantal; Treilleux, Isabelle; Dumontet, Charles; Cardoso, Fátima; Fellous, Arlette; Gancberg, David; Bissery, Marie Christine; Paesmans, Marianne; Larsimont, Denis; Piccart, Martine; Leo, Angelo Di

doi:10.3816/cbc.2002.n.037

Cited by 72 publications

(48 citation statements)

References 20 publications

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“…As in the case of doxorubicin, most published studies contain significant weaknesses (retrospective and unplanned nature, and small sample size) and therefore, the real predictive values of HER2 [56,57], microtubule associated parameters [58][59][60], and ki-activity, while the remaining markers (PR, HER2, TOP2A gene alterations or topo2a protein expression, tau protein, p27, Ki67) were not.…”

Section: Discussionmentioning

confidence: 99%

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Martín

Romero

Cheang

et al. 2011

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 99%

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Martín

Romero

Cheang

et al. 2011

Breast Cancer Res Treat

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“…The observation that tau expression modulates response to paclitaxel is unique but consistent with previously reported data. Expression of tau outside the central nervous system, including in epithelial cells, is well documented (21)(22)(23). Tau contains an imperfect estrogen response element upstream of its promoter and is an estrogen-induced protein in cultured neurons and in MCF-7 cells (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Microtubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer

Rouzier

Rajan

Wagner

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

378

301

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Breast cancers show variable sensitivity to paclitaxel. There is no diagnostic test to identify tumors that are sensitive to this drug. We used U133A chips to identify genes that are associated with pathologic complete response (pCR) to preoperative paclitaxelcontaining chemotherapy in stage I-III breast cancer (n ‫؍‬ 82). Tau was the most differentially expressed gene. Tumors with pCR had significantly lower (P < 0.3 ؋ 10 ؊5 ) mRNA expression. Tissue arrays from 122 independent but similarly treated patients were used for validation by immunohistochemistry. Seventy-four percent of pCR cases were tau protein negative; the odds ratio for pCR was 3.7 (95% confidence interval, 1.6 -8.6; P ϭ 0.0013). In multivariate analysis, nuclear grade (P < 0.01), age <50 (P ϭ 0.03), and taunegative status (P ϭ 0.04) were independent predictors of pCR. Small interfering RNA experiments were performed to examine whether down-regulation of tau increases sensitivity to chemotherapy in vitro. Down-regulation of tau increased sensitivity of breast cancer cells to paclitaxel but not to epirubicin. Tubulin polymerization assay was used to assess whether tau modulates binding of paclitaxel to tubulin. Preincubation of tubulin with tau resulted in decreased paclitaxel binding and reduced paclitaxelinduced microtubule polymerization. These data suggest that low tau expression renders microtubules more vulnerable to paclitaxel and makes breast cancer cells hypersensitive to this drug. Low tau expression may be used as a marker to select patients for paclitaxel therapy. Inhibition of tau function might be exploited as a therapeutic strategy to increase sensitivity to paclitaxel. adjuvant therapy ͉ drug resistance

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“…A previous study on advanced breast cancer patients 38 showed the ability of Class II b tubulin to predict docetaxel cytotoxic activity. The only other available study 39 on breast cancer patients treated with neoadjuvant docetaxel reported that Class III b tubulin mRNA increase was associated with a poorer probability of clinical response to docetaxel.…”

Section: Discussionmentioning

confidence: 99%

Cytoskeleton and paclitaxel sensitivity in breast cancer: The role of β‐tubulins

Tommasi¹,

Mangia²,

Lacalamita³

et al. 2007

Intl Journal of Cancer

139

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The antineoplastic effect of paclitaxel is mainly related to its ability to bind the b subunit of tubulin, thus preventing tubulin chain depolarization and inducing apoptosis. The relevance of the Class I b-tubulin characteristics have also been confirmed in the clinical setting where mutations of paclitaxel-binding site of b-tubulin Class I have been related to paclitaxel resistance in non small cell lung and ovarian cancers. In the present study, we verified the hypothesis of a relationship between molecular alterations of b-tubulin Class I and paclitaxel sensitivity in a panel of breast cell lines with different drug IC 50 . The Class I b-tubulin gene cDNA has been sequenced detecting heterozygous missense mutations (exon 1 and 4) only in MCF-7 and SK-BR-3 lines. Furthermore, the expression (at both mRNA and protein level) of the different isotypes have been analyzed demonstrating an association between low cell sensitivity to paclitaxel and Class III b-tubulin expression increasing. Antisense oligonucleotide (ODN) experiments confirmed that the inhibition of Class III b-tubulin could at least partially increase paclitaxel-chemosensitivity. The hypothesis of a relationship between b-tubulin tumor expression and paclitaxel clinical response has been finally verified in a series of 92 advanced breast cancer patients treated with a first line paclitaxel-based chemotherapy. Thirty-five percent (95% CI: 45-31) of patients with high Class III b-tubulin expression showed a disease progression vs. only 7% of patients with low expression (35% vs. 7%, p < 0.002). Our study suggests that Class III b-tubulin tumor expression could be considered a predictive biomarker of paclitaxel-clinical resistance for breast cancer patients. ' 2007 Wiley-Liss, Inc.

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Microtubule-Associated Parameters as Predictive Markers of Docetaxel Activity in Advanced Breast Cancer Patients: Results of a Pilot Study

Cited by 72 publications

References 20 publications

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Microtubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer

Cytoskeleton and paclitaxel sensitivity in breast cancer: The role of β‐tubulins

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