Association of p53 codon 72 polymorphism with resistance to adjuvant therapy in primary breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10520-10520
Author(s):  
T. Toyama ◽  
Z. Zhang ◽  
M. Hamguchi ◽  
N. Kondo ◽  
H. Iwase ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Systemic Therapy ◽  
Proportional Hazards ◽  
Adjuvant Systemic Therapy ◽  
Breast Cancer Patients ◽  
Mdm2 Snp309 ◽  
P53 Codon 72 ◽  
Codon 72 ◽  
Proportional Hazards Regression

10520 Background: Single-nucleotide polymorphisms (SNPs) in codon 72 of the p53 gene and in the promoter region of the MDM2 gene (SNP309) have been suggested to play a role in many cancers. We investigated whether these SNPs were associated with patient outcome and influence of adjuvant systemic therapy. Method: The genotypes of p53 codon 72 and MDM2 SNP309 were defined among 557 primary Japanese breast cancer patients (median follow-up, 61.7 months). The effects of several variables on survival were tested by Cox's proportional hazards regression analysis. Results: We showed that the Pro/Pro genotype of p53 codon 72 was significantly associated with poorer disease-free survival (DFS) than other genotypes by Kaplan-Meier analysis (P = .049) and multivariate Cox's proportional hazards regression analysis (P = .047, risk ratio of recurrence = 1.67), whereas MDM2 SNP309 status was not associated with DFS. The association of the Pro/Pro p53 genotype with poorer DFS was especially significant in patients who received adjuvant chemotherapy (P = .009). In contrast, among the patients who had received adjuvant hormonal therapy or no adjuvant systemic therapy, p53 codon 72 genotype was not associated with DFS. Conclusion: The Pro/Pro genotype of p53 codon 72 appears to be an independent prognostic marker of breast cancer patients that have received adjuvant systemic therapy, particularly chemotherapy, and may be predictive of therapy resistance. [Table: see text] No significant financial relationships to disclose.

Validation of Adjuvant!Online on Slovenian collective of early breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11532-e11532
Author(s):  
M. Ravnik ◽  
A. Sadikov ◽  
N. Snoj ◽  
P. Nussdorfer ◽  
T. Cufer
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Systemic Therapy ◽  
First Generation ◽  
Local Therapy ◽  
Adjuvant Systemic Therapy ◽  
Breast Cancer Patients ◽  
Small Group Size ◽  
Positive Effect

e11532 Background: Adjuvant!Online is a very useful tool for prognosis assessment of early breast cancer (EBC) patients. In the validation study, made on mostly untreated (45%) Canadian EBC patients, Adjuvant!Online proved to be a very reliable prognostic tool. The aim of our study was to validate Adjuvant!Online on EBC patients mainly treated with some kind of adjuvant systemic therapy. Methods: 753 EBC patients diagnosed and treated at the Institute of Oncology Ljubljana, Slovenia, with at least 10-year follow-up were included into the study. All patients received radical local therapy. Adjuvant chemotherapy (ChT) was either CMF or anthracycline-based schema and hormonal therapy (HT) was mainly tamoxifen. Adjuvant!Online 8.0 individual prediction of OS was calculated (with default value of “minor problems” as comorbidity for all patients). The average prediction over all patients was compared to the observed 10-year OS. Results: The predicted and observed 10-year OS of the whole group were 65.5% and 61.5%, respectively. The differences between predicted and observed OS did not differ substantially in the subgroups of patients stratified according to the classical prognostic factors, however, a large difference was found when stratifying by adjuvant systemic therapy. The puzzling difference in patients without systemic therapy (ST) can be both due to small group size and due to special selection of these patients (comorbidity). Conclusions: According to our observation, Adjuvant!Online is a reliable tool for prognosis assessment in EBC patients treated with HT, but it seems to overestimate prognosis in patients treated with ChT, alone or in combination with HT. This is evident even for our collective of EBC patients mainly treated with the first generation ChT - CMF or anthracyclines. Apparently, both Adjuvant!Online and Overview overestimate the positive effect of ChT, disregarding the biologic characteristics of the tumors and inherent effect of HT in HR+ patients. [Table: see text] No significant financial relationships to disclose.

Demographic features and prognostic profiles of breast cancer patients presenting with nipple discharge in Chinese population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22204-e22204
Author(s):  
W. Yin ◽  
G. Di ◽  
G. Liu ◽  
J. Wu ◽  
J. Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Tumor Size ◽  
Chinese Population ◽  
Proportional Hazards ◽  
Nipple Discharge ◽  
Breast Cancer Patients ◽  
Proportional Hazards Regression ◽  
Demographic Features

e22204 Background: Breast cancer patients with nipple discharge (ND) may constitute a distinct clinical entity compared to those without ND, which has not been well elucidated in previous reports. We sought to analyze the demographic features and prognostic profiles of breast cancer patients presenting with nipple discharge in Chinese population. Methods: A total of 3234 patients, categorized as ND (2.47%) and non-nipple discharge (NND; 97.53%) according to different initial signs, were retrospectively analyzed. Survival curves were performed with Kaplan-Meier method and annual recurrence hazard was estimated by hazard function. Results: ND group tended to have smaller tumors and less axillary lymph node (ALN) involvement than NND group (P < 0.05). In the univariate analysis, we found significantly different recurrence-free survivals (RFS) between subgroups (P = 0.0182), with the rate of 77.78% for ND group and 72.46% for the other at the 11th year respectively. In Cox proportional hazards regression analysis, we found that tumor size (P < 0.001), ALN status (P < 0.001) were independent prognostic factors for RFS. To further evaluate whether prognostic effect of ND status remained unabated over time, the test for lack of proportionality was performed. However, it was statistically significant (global test, P = 0.039), which hinted at a demand for the employment of Cox non-proportional hazards regression in this analysis. In time dependent Cox model, ND status (P = 0.0495) as well as ERBB2 status (P = 0.017), tumor size (P < 0.001), ALN status (P < 0.001) were independent prognostic factors when ND and ERBB2 status were taken as time-varying covariates. Annual hazard rates for recurrence remained lower on ND group until approximately 4.5 years after surgery, while the situation was just the opposite thereafter. Conclusions: Our findings suggested that demographic features and prognostic profiles were quite different between breast cancers presenting with and without ND in Chinese population, which may indirectly uncover distinct biological behaviors and potentially enlighten novel therapeutic approaches for patients with different initial signs. No significant financial relationships to disclose.

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