Gene expression signature of TP53 but not its mutation status predicts response to sequential paclitaxel and 5-FU/epirubicin/cyclophosphamide in human breast cancer

Oshima, Kazuteru; Naoi, Yasuto; Kishi, Kazuki; Nakamura, Yukiko; Iwamoto, Takashi; Shimazu, Kenzo; Nakayama, Takahiro; Kim, Seung Jin; Baba, Yosuke; Tamaki, Yasuhiro; Noguchi, Shinzaburo

doi:10.1016/j.canlet.2011.03.027

Cited by 27 publications

(32 citation statements)

References 27 publications

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“…[18][19][20][21][22][23] Considering primary (pre-surgical) treatment of breast cancer, TP53 mutations have been associated with anthracycline and mitomycin resistance, 12,[24][25][26] but not with taxane resistance; 26,27 similarly, one study evaluating efficacy of taxanes in the adjuvant setting 28 and two studies evaluating anthracyclines and taxanes administered in concert, or sequentially, found no effect of TP53 mutation status on response. 29,30 Yet, there is evidence at variance. Thus, de The and colleagues 31 found TP53 mutations to predict improved response to chemotherapy in breast cancer; this effect, however, was observed among patients receiving cyclophosphamide at high doses in concert with anthracyclines.…”

Section: Tp53mentioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

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Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

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Section: Tp53mentioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

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“…HER2 amplification was determined by means of fluorescence in situ hybridization (FISH) as previously described. (26) For FISH scoring, a tumor was considered to be HER2 amplified when the FISH ratio was ! 2.0.…”

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confidence: 99%

GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER‐negative breast cancer

et al. 2012

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The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/ epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors. (Cancer Sci 2012; 103: 913-920) N eoadjuvant chemotherapy (NAC) for primary breast cancer patients is known to enhance the operability of patients with advanced tumors previously considered inoperable, as well as making breast-conserving surgery more feasible for patients for whom such surgery was previously not feasible due to large tumor size. In addition, it is well established that patients who show a pathological complete response (pCR) to NAC can have a better prognosis than those who do not, (1)(2)(3) so the response to NAC can provide valuable information regarding patient prognosis. These advantages of NAC have led to its widespread use including recently for a growing number of breast cancer patients. However, pCR rates for NAC of only 20-30% of patients are still rather low. (4) Because adverse effects of various degrees of severity are seen in virtually all patients, it seems to be very important to develop predictive factors for the response to NAC to avoid the unnecessary use of NAC for patients who are unlikely to derive benefits from such therapy.Among predictive factors, estrogen receptor (ER), progesterone receptor (PR), HER2, histological grade (HG) and Ki-67 have been most extensively studied and significant associations of ER negativity, PR negativity, HER2 amp...

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“…For example, some findings suggest that HER2 overexpression or gene amplification together with Topo IIα positive or negative status could collectively predict the response to anthracycline-based chemotherapy; however, this finding has been questioned by other studies (Di Leo et al, 2002;Järvinen et al, 2003;Arpino et al, 2005;Fritz et al, 2005;Harris et al, 2009;Munro et al, 2010). Moreover, an increasing number of factors, such as Ki67, oncoprotein K-RAS, and tumor suppressor p53, have been proposed to affect neoadjuvant chemotherapy in breast cancer, but the overall consensus remains inconclusive (Bonnefoi et al, 2011;Dowsett et al, 2011;Generali et al, 2011;Oshima et al, 2011;Petrarca et al, 2011). However, a few studies conducted at major breast cancer centers in China have indicated that the HER2 and Topo IIα status together may have a predictive role in breast cancer therapy (Zhu et al, 2008;Li et al, 2011).…”

Section: Introductionmentioning

confidence: 43%

Predictive Factors Determining Neoadjuvant Chemotherapy Outcomes in Breast Cancer - a Single Center Experience

Xiang²,

He³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo IIα status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo IIα status. Based on our findings, we propose that HR, HER-2 and Topo IIα are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo IIα expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.

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Gene expression signature of TP53 but not its mutation status predicts response to sequential paclitaxel and 5-FU/epirubicin/cyclophosphamide in human breast cancer

Cited by 27 publications

References 27 publications

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER‐negative breast cancer

Predictive Factors Determining Neoadjuvant Chemotherapy Outcomes in Breast Cancer - a Single Center Experience

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