A Study of the Value of p53, HER2, and Bcl-2 in the Prediction of Response to Doxorubicin and Paclitaxel as Single Agents in Metastatic Breast Cancer: A Companion Study to EORTC 10923

Hamilton, Anne; Larsimont, Denis; Paridaens, Robert; Drijkoningen, Maria; Vijver, Marc J. van de; Bruning, P.F.; Hanby, Andrew M.; Houston, Stephen; Treilleux, Isabelle; Guastalla, Jean Paul; Vreckem, A. Van; Sylvester, Richard; Piccart, Martine

doi:10.3816/cbc.2000.n.020

Cited by 43 publications

(18 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have also failed to show a significant association of p53 and BRCA-1 expression with a pathologic response. Actually, several conflicting results have been reported on the value of these biomarkers in the prediction of a response to taxanes (24,26,40,42). On the other hand, we have been able to show that negative ER status showed a significant association with a good pathologic response, being consistent with the previous studies (43,44).…”

Section: Discussionsupporting

confidence: 91%

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

Kim

Miyoshi

Taguchi

et al. 2005

Clinical Cancer Research

164

115

View full text Add to dashboard Cite

Purpose: Thioredoxin overexpression is suggested to be associated with resistance to several chemotherapeutic agents in vitro. In the present study, it has been studied whether or not high thioredoxin expression is associated with resistance to docetaxel therapy in breast cancer patients. Patients and Methods: Sixty-three primary breast cancer patients were treated with docetaxel (60 mg/m 2 , q3w) for four cycles in the neoadjuvant setting. Expression of thioredoxin, estrogen receptor (ER), p53, BRCA-1, and Bcl-2 in tumor tissues obtained before docetaxel therapy was studied by immunohistochemistry (thioredoxin, p53, BRCA-1, and Bcl-2) and enzyme immunoassay (ER), and relationship of expression of these biomarkers with a pathologic response was investigated.Results: There was no significant correlation between the expression of p53, BRCA-1, or Bcl-2 and a response to docetaxel. However, tumors with high thioredoxin expression showed a significantly lower response rate (0%) than those with low thioredoxin expression (30.6%; P = 0.018) and ER-negative tumors showed a significantly higher response rate (32.4%) than ER-positive tumors (10.7%; P = 0.043).Thioredoxin expression significantly increased after docetaxel therapy (mean, 56.1%) as compared with that before docetaxel therapy (mean, 28.6%; P < 0.0001) but there was no significant association between the extent of increase in thioredoxin expression and response. Conclusion: High thioredoxin expression in prechemotherapy tumor samples, but not the increase in thioredoxin expression induced by docetaxel, is associated with resistance to docetaxel in breast cancer.Thioredoxin and ER might be clinically useful in the prediction of a response to docetaxel. Docetaxel, which belongs to taxanes, is one of the most powerful anticancer drugs for breast cancer, and an increasing number of breast cancer patients have been treated with docetaxel not only in the metastatic setting but also in the adjuvant setting, and more recently, in the neoadjuvant setting. The response rate of docetaxel, however, is f50% even in the first-line chemotherapy and it decreases to 20% to 30% in the second-or third-line chemotherapy (1 -3). Therefore, it is of vital importance to select the patients who are very likely to respond to docetaxel to eliminate the unnecessary treatment.

show abstract

Section: Discussionsupporting

confidence: 91%

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

Kim

Miyoshi

Taguchi

et al. 2005

Clinical Cancer Research

164

115

View full text Add to dashboard Cite

show abstract

“…A few studies evaluated the association between HER-2 expression and response to taxanes but, more recentely, Hamilton et al 44 and Poznak et al 45 confirmed that HER-2 expression was not related with response to single-agent taxane therapy. Another tumor biomarker suggested as predictive of paclitaxel clinical response has been tumor apoptosis but, also in this case, Kandioler et al 46 recently reported negative results.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…[11][12][13][14][15][16] Our study demonstrates that HER2 overexpression is associated with a higher sensitivity to HDCT (conversion rate 87.5% in HER2-positive patients vs 37% in HER2-negative patients). However, this greater chemosensitivity is not translated into a positive impact on median PFS, since it was significantly shorter for HER2-positive patients (15.3 vs 21.3 months).…”

Section: Discussionmentioning

confidence: 94%

“…[11][12][13][14][15][16] In conclusion, patients with MBC overexpressing HER2 are not good candidates for HDCT. However, since these patients have an increased chemosensitivity, new treatment strategies, including HDCT and HER2 targeted therapies, should be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10] On the other hand, HER2 overexpression may correlate with a better response to doxorubicin and paclitaxel. [11][12][13][14][15][16] The efficacy of high-dose chemotherapy in metastatic breast cancer (MBC) is yet to be established. 17 Therefore, it is of interest to verify whether, among the heterogeneous MBC population, a subset of patients might benefit from more aggressive treatments.…”

Section: Metastatic Breast Cancermentioning

confidence: 99%

See 1 more Smart Citation

HER2 overexpression as a prognostic factor in metastatic breast cancer patients treated with high-dose chemotherapy and autologous stem cell support

Guarneri

Bengala²,

Orlandini³

et al. 2004

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:We retrospectively evaluated the predictive and prognostic role of HER2 expression in 44 metastatic breast cancer (MBC) patients treated with high-dose consolidation chemotherapy (HDCT) and autologous stem cell support after induction chemotherapy (IC) with six courses of epirubicin þ paclitaxel (22 patients) or gemcitabine þ epirubicin þ paclitaxel (22 patients). HER2 expression was evaluated by an immunohistochemical method (Herceptest, Dako). A total of 13 patients (29.5%) showed a HER2 overexpression (score 3 þ ). After IC, nine patients were in complete response (CR), 30 in partial response (PR), and five in stable disease (SD); after HDCT, 20 (45.5%) obtained a CR, and 23 were in PR, for a conversion rate of 48.5%. Conversion rate for HER2-positive patients was 87.5 vs 37% for HER2-negative patients (P ¼ 0.018). The median progressionfree (PFS) and overall survivals (OS) were 17.6 (95% CI 13.2-22.0) and 44 (95% CI 25.9-62.3) months, respectively. Patients with HER2 overexpression experienced a significantly (P ¼ 0.0042) shorter median PFS (15.3 months, 95% CI 11.1-19.5) compared to HER2-negative patients (21.3 months,). The median OS was 27.6 months (95% CI 4.5-50.7) in HER2-positive patients and 50.3 months (95% CI 38.7-62.0) in HER2-negative patients (P ¼ 0.345). These results indicate that HER2 overexpression predicts a worse outcome for patients with MBC treated with HDCT, despite the high CR rate obtained in this subset of patients.

show abstract

A Study of the Value of p53, HER2, and Bcl-2 in the Prediction of Response to Doxorubicin and Paclitaxel as Single Agents in Metastatic Breast Cancer: A Companion Study to EORTC 10923

Cited by 43 publications

References 21 publications

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

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

HER2 overexpression as a prognostic factor in metastatic breast cancer patients treated with high-dose chemotherapy and autologous stem cell support

Contact Info

Product

Resources

About