scholarly journals Mutant p53 and Twist1 Co-Expression Predicts Poor Prognosis and Is an Independent Prognostic Factor in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yong-Qu Zhang ◽  
Fan Zhang ◽  
Yun-Zhu Zeng ◽  
Min Chen ◽  
Wen-He Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Stage ◽  
Lymph Node Involvement ◽  
Mutant P53 ◽  
Breast Cancer Patients ◽  
P53 Expression ◽  
Free Survival ◽  
Node Involvement ◽  
Patient Prognosis

PurposeThe basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease.MethodsTwist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort.ResultsOf the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%)vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217–7.499, P = 0.017) and OS (95% CI = 1.009–9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients.ConclusionsOur results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome.

scholarly journals Influence of Covariates on Involved Lymph Nodes in Primary Breast Cancer Patients: Mixture Distribution Zero-Inflated Modeling Methodological Framework

2020 ◽  
Author(s):  
Madiha Liaqat ◽  
Shahid Kamal ◽  
Florian Fischer ◽  
Nadeem Zia
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Negative Binomial ◽  
Lymph Node Involvement ◽  
Breast Cancer Patients ◽  
Node Involvement ◽  
Study Population

Abstract Background: Involvement of lymph nodes has been an integral part of breast cancer prognosis and survival. This study aimed to explore factors influencing on the number of auxiliary lymph nodes in women diagnosed with primary breast cancer by choosing an efficient model to assess excess of zeros and over-dispersion presented in the study population. Methods: The study is based on a retrospective analysis of hospital records among 5,196 female breast cancer patients in Pakistan. Zero-inflated Poisson and zero-inflated negative binomial modeling techniques are used to assess the association between under-study factors and the number of involved lymph nodes in breast cancer patients. Results: The most common breast cancer was invasive ductal carcinoma (54.5%). Patients median age was 48 years, from which women aged 46 years and above are the majority of the study population (64.8%). Examination of tumors revealed that over 2,662 (51.2%) women were ER-positive, 2,652 (51.0%) PR-positive, and 2,754 (53.0%) were Her2.neu-positive. The mean tumor size was 3.06 cm and histological grade 1 (n=2021, 38.9%) was most common in this sample. The model performance was best in the zero-inflated negative binomial model. Findings indicate that most factors related to breast cancer have a significant impact on the number of involved lymph nodes. Age is not contributed to lymph node status. Women having a larger tumor size suffered from greater number of involved lymph nodes. Tumor grades 11 and 111 contributed to higher numbers of positive lymph node.Conclusions: Zero-inflated models have successfully demonstrated the advantage of fitting count nodal data when both “at-harm” (lymph node involvement) and “not-at-harm” (no lymph node involvement) groups are important in predicting disease on set and disease progression. Our analysis showed that ZINB is the best model for predicting and describing the number of involved nodes in primary breast cancer, when overdispersion arises due to a large number of patients with no lymph node involvement. This is important for accurate prediction both for therapy and prognosis of breast cancer patients.

Breast-conserving surgery after neoadjuvant chemotherapy for stage III breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11532-e11532
Author(s):  
Hee-Chul Shin ◽  
Wonshik Han ◽  
Hyeong-Gon Moon ◽  
Woo Kyung Moon ◽  
Seock-Ah Im ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Stage ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Stage Iii Breast Cancer

e11532 Background: Neoadjuvant chemotherapy (NCT) is a reasonable option for operable breast cancer in terms of downsizing large tumor and increasing the rate of breast-conserving surgery (BCS). However, BCS in patients with large breast tumors down-staged by NCT remains still controversial because of the possibility of residual tumor and resistance to NCT. Aims of this study were to evaluate the long-term survival results of patients who received NCT and BCS compared to patients who received BCS first and to compare recurrence and survival rates between patients who received preplanned BCS and those who received down-staged BCS among patients who underwent NCT. Methods: Between 2000 and 2007, 70 patients with clinical stage III breast cancer who received BCS after NCT (NCT group) and 72 patients with clinical stage III breast cancer who underwent BCS first (Surgery group) were retrospectively reviewed. Among 70 patients received NCT, 45 patients (64.3%) received preplanned BCS (preplanned BCS group) and 25 patients (35.7%) received down-staged BCS (down-staged BCS group). The long-term results including ipsilateral breast tumor recurrence (IBTR), locoregional recurrence (LRR), disease recurrence and survival rates were compared with groups. Results: There was no significant difference in IBTR-free survival, LRR-free survival rates, disease-free survival and overall survival rates between the NCT and the Surgery group (p=0.971, p=0.294, p=0.863 and p=0.933, respectively). Among patients who received NCT, IBTR-free survival, LRR-free survival, disease-free survival and overall survival rates was not also different between the preplanned BCS group and the down-staged BCS group (p=0.278, p=0.501, p=0.776 and p=0.412, respectively). Conclusions: Our study demonstrated that patients who received BCS after NCT showed similar long-term resutls compared to patients who received BCS first in clinical stage III breast cancer patients. Also, down-staged BCS shows is oncologically as safe as preplanned BCS in clinical stage III breast cancer patients in terms of recurrence and survival.

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