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Ref Type Journal Article
PMID (16243804)
Authors Xu Y, Yao L, Ouyang T, Li J, Wang T, Fan Z, Lin B, Lu Y, Xie Y
Title p53 Codon 72 polymorphism predicts the pathologic response to neoadjuvant chemotherapy in patients with breast cancer.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 11
Issue 20
Date 2005 Oct 15
URL
Abstract Text Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer.One hundred and ten operable breast cancer patients received anthracycline-based neoadjuvant chemotherapy and p53 codon 72 polymorphism status was analyzed by PCR-RFLP.The distribution of initial clinical stage, tumor size, estrogen receptor or progesterone receptor status, menopausal status, or erbB2 expression was not significantly different among the polymorphic variants. However, we found that only 13% (3 of 23) of patients with the Pro/Pro variant had a good pathologic response, defined as a complete pathologic response or minimal residual disease. In comparison, 40% (22 of 55) or 37.5% (12 of 32) of patients with the Pro/Arg or Arg/Arg variant had a good pathologic response (P = 0.019). Moreover, patients with the Pro/Pro variant were more likely to have a positive axillary lymph node status than those with the Pro/Arg or Arg/Arg variant (P = 0.007). Furthermore, in multivariate analysis, p53 codon 72 polymorphism was found to be a strong predictor of pathologic response (odds ratio 6.7, 95% confidence interval, 1.4-31.2; P = 0.016).Our study indicates that breast cancer patients with the Pro/Pro variant may be less sensitive to anthracycline-based treatment than those with the Pro/Arg or Arg/Arg variant and suggests that analysis of p53 codon 72 polymorphism may provide a simple predictive marker for selecting the right breast cancer patients to anthracycline-based neoadjuvant chemotherapy in clinical setting.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 P72R estrogen-receptor negative breast cancer sensitive Cyclophosphamide + Doxorubicin + Fluorouracil Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R who were estrogen receptor negative had a more favorable response to Doxil (doxorubicin) in combination with Adrucil (fluorouracil) and Cytoxan (cyclophosphamide) (PMID: 16243804). 16243804
TP53 P72R breast cancer predicted - sensitive Pegylated liposomal-doxorubicin Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations were reported to have a better response to anthracycline-based neoadjuvant therapies (PMID: 16243804). 16243804
TP53 P72R breast cancer predicted - sensitive Daunorubicin Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations were reported to have a better response to anthracycline-based neoadjuvant therapies (PMID: 16243804). 16243804
TP53 P72R breast cancer predicted - sensitive Daunoxome Phase I Actionable In a Phase I clinical trial, breast cancer patients harboring TP53 P72R mutations were reported to have a better response to anthracycline-based neoadjuvant therapies (PMID: 16243804). 16243804