&lt;i&gt;TP53&lt;/i&gt; Status and Response to Chemotherapy in Breast Cancer

Bertheau, Philippe; Espié, Marc; Turpin, Elisabeth; Lehmann, Jacqueline; Plassa, Louis-François; Varna, Mariana; Janin, Anne; Thé, Hugues de

doi:10.1159/000123851

Cited by 96 publications

(84 citation statements)

References 128 publications

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“…In parallel all clinicopathological variables available from patient records were statistically evaluated in relation to p53 status. The frequency of p53 mutations in our cohort of breast cancer patients was 25.7% which is consistent with other reports (10). Cases with mutations that did not change the resulting AA (silent mutations) were counted as wt p53.…”

Section: Resultssupporting

confidence: 91%

Influence of mutation type on prognostic and predictive values of TP53 status in primary breast cancer patients

et al. 2014

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Abstract. High rates of mutation in the TP53 tumor suppressor gene have been found in many human cancers, including breast tumors, making p53 one of the most studied proteins in oncology. However, the prognostic and predictive value of alterations in this gene remains ambiguous. To analyze the clinical value of somatic TP53 mutations, we collected clinical and molecular data on 210 women with primary breast cancer. We found significant associations of p53 mutations with tumor grade, metastasis, molecular subtype, Her2 status and inverse correlations with estrogen and progesterone receptor status. Cox proportional hazard analysis confirmed a strong prognostic value of p53 mutation for overall survival rate and highlighted significant interactions with lymph node involvement and tumor size. In relation to treatment options, TP53 mutations were associated with poor response to anthracyclines and radiotherapy. Categorization of TP53 mutations according to their type and location revealed that patients with nonsense mutation have the poorest prognosis in comparison with wild-type cases and other types of mutations in this gene. Classification of TP53 mutations with respect to the degree of disturbance of protein structure showed association of disruptive mutations with poorer patients' outcome in contrast to wild-type and non-disruptive mutations. In conclusion, the present study confirms p53 as a potential predictive and prognostic factor in oncology practice and highlights the growing evidence that distinct types of mutations have different clinical impacts.

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Section: Resultssupporting

confidence: 91%

Influence of mutation type on prognostic and predictive values of TP53 status in primary breast cancer patients

et al. 2014

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“…Earlier studies by Bertheau et al (2008) and Agrawal et al (2009) showed results ranging from 14-58% of p53 (+) protein overexpression in breast cancer tissues. The findings from this present study reported that overexpression of p53 (+) protein was found in 40% (44/111) of the overall breast cancer cases.…”

Section: Discussionmentioning

confidence: 90%

Expression of p53 Protein in Premenopausal Women as Risk Factors for Breast Cancer

Saad¹

2016

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ABSTRAK Mutasi telah dikenalpasti berlaku sebelum pembentukan pelbagai jenis kanser. Mutasi di dalam gen p53 boleh dijumpai dalam kanser payudara. Objektif kajian ini adalah untuk menentukan korelasi antara protein p53 dengan wanita dalam usia pra-menopaus. Sebanyak 111 tisu kanser payudara telah dikaji untuk ekspresiGenetic factors in the pathogenesis of breast cancer can be ascribed to be inherited susceptibility. Three genes (p53, BRCA1, and BRCA2) were identified, which may alter the formation of tumour suppressor genes. In breast cancer p53 mutation/alteration are reported in 50% of primary carcinomas (Callahan 1992;Muller & Vousden 2013;Bertheau et al. 2013). in premenopausal age. A total of 111 breast cancer tissues were examined for p53 protein expression by IHC. The results showed that majority (36.9%; n=41/111) who were more than 41 yrs, overexpressed positive p53 (+) protein category and 2.7% (n=3/111) aged 41 yrs and less, showed less positive p53 (+) protein category. However, the Fishers exact test, indicated that, there was no significant correlation between participant's age group with p53 protein category (χ 2 (1) = 0.78; p =0.52) and no correlation strength was indicated (Cramer's V coefficient = 0.08; p =0.37), respectively. The risk estimate showed probability of p53 (+) protein being overexpressed in the age group < 41 yrs was 0.66 times less likely compared to the age group > 41 yrs. In conclusion, with or without overexpression of p53 protein, women above 41 yrs were found to have greater risk.

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“…The explanation behind these findings is likely to be complex and further investigations of the triad relationship between HAGE, TILs, and response to chemotherapy are warranted. The higher rate of response to a given chemotherapy could probably result from an accumulation of DNA damage, abnormal mitoses, and subsequent mitotic catastrophe (30,31). The mechanisms of mitotic catastrophe are unknown, but it likely results from a combination of deficient cell-cycle checkpoints and cellular damage.…”

Section: Discussionmentioning

confidence: 99%

HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis

Abdel-Fatah

McArdle

Agarwal

et al. 2016

Clinical Cancer Research

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Purpose: The expression of HAGE as a novel prognostic and predictive tool was assessed in 1,079 triple-negative breast cancers (TNBC).Experimental Design: HAGE protein expression was investigated in an early primary TNBC (EP-TNBC; n ¼ 520) cohort who received adjuvant chemotherapy (ACT) and in a locally advanced primary TNBC cohort who received anthracycline combination Neo-ACT (n ¼ 110; AC-Neo-ACT). HAGE-mRNA expression was evaluated in the METABRIC-TNBC cohort (n ¼ 311) who received ACT and in a cohort of patients with TNBC who received doxorubicin/cyclophosphamide Neo-ACT, followed by 1:1 randomization to ixabepilone (n ¼ 68) or paclitaxel (n ¼ 64) as part of a phase II clinical trial. Furthermore, a cohort of 128 tumors with integrated HAGE gene copy number changes, mRNA, and protein levels were analyzed.Results: In patients with EP-TNBC, who were chemotherapy-na€ ve, high HAGE protein expression (HAGE þ ) was associated with a higher risk of death [HR, 1.3; 95% confidence interval (CI), 1.2-1.5; P ¼ 0.000005] when compared with HAGE À cases. Patients who received ACT and expressed mRNA-HAGE þ were at a lower risk of death than those who were mRNA-HAGE À (P ¼ 0.004). The expression of HAGE was linked to the presence of tumor-infiltrating lymphocytes (TIL), and both features were found to be independent predictors for pathologic complete response (pCR, P < 0.001) and associated with prolonged survival (P < 0.01), following AC-Neo-ACT. In patients with residual disease, HAGE þ had a 2-fold death risk increase (P ¼ 0.018) compared with HAGE À .Conclusions: HAGE expression is a potential prognostic marker and a predictor of response to anthracycline treatment in TNBC. A prospective clinical trial to examine the therapeutic value of HAGE for TNBC cases is warranted.

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<i>TP53</i> Status and Response to Chemotherapy in Breast Cancer

Cited by 96 publications

References 128 publications

Influence of mutation type on prognostic and predictive values of TP53 status in primary breast cancer patients

Influence of mutation type on prognostic and predictive values of TP53 status in primary breast cancer patients

Expression of p53 Protein in Premenopausal Women as Risk Factors for Breast Cancer

HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis

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