scholarly journals PTHrP, A Biomarker for CNS Metastasis in Triple-Negative Breast Cancer and Selection for Adjuvant Chemotherapy in Node-Negative Disease

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Gloria Assaker ◽  
Anne Camirand ◽  
Bassam Abdulkarim ◽  
Atilla Omeroglu ◽  
Jean Deschenes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Node Negative ◽  
Cancer Genome Atlas

Abstract Background Triple-negative breast cancer (TNBC) is characterized by poor prognosis and lack of targeted therapies and biomarkers to guide decisions on adjuvant chemotherapy. Parathyroid hormone-related protein (PTHrP) is frequently overexpressed in breast cancer and involved in proliferation and metastasis, two hallmarks of poor prognosis for node-negative breast cancer. We investigated the prognostic value of PTHrP with respect to organ-specific metastasis and nodal status in TNBC. Methods We assessed PTHrP expression using immunohistochemistry in a clinically annotated tissue microarray for a population-based study of 314 patients newly diagnosed with TNBC, then analyzed its correlation to progression and survival using Kaplan-Meier and Cox regression analyses. The Cancer Genome Atlas (TCGA) validation analysis was performed through Bioconductor. All statistical tests were two-sided. Results PTHrP overexpression (160 of 290 scorable cases, 55.2%) was statistically significantly associated in univariate analysis with decreased overall survival (OS) in our cohort (P = .0055) and The Cancer Genome Atlas (P = .0018) and decreased central nervous system (CNS)-progression-free survival (P = .0029). In multivariate analysis, PTHrP was a statistically significant independent prognostic factor for CNS-progression-free survival in TNBC (hazard ratio [HR] = 5.014, 95% confidence interval [CI] = 1.421 to 17.692, P = .0122) and for OS selectively in node-negative TNBC (HR = 2.423, 95% CI = 1.129 to 5.197, P = .0231). Strikingly, PTHrP emerged as the only statistically significant prognostic factor (HR = 2.576, 95% CI = 1.019 to 6.513, P = .0456) for OS of low-clinical risk node-negative patients who did not receive adjuvant chemotherapy. Conclusions PTHrP is a novel independent prognostic factor for CNS metastasis and adjuvant chemotherapy selection of low-clinical risk node-negative TNBC. Its predictive value needs to be prospectively assessed in clinical trials.

Immediate and long-term results of the first line chemotherapy in patients with metastatic triple negative breast cancer. Final analysis of randomized study

2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

scholarly journals BRAF V600E Mutation in Triple-Negative Breast Cancer: A Case Report and Literature Review

2021 ◽  
pp. 1-7
Author(s):  
Liye Wang ◽  
Qianyi Lu ◽  
Kuikui Jiang ◽  
Ruoxi Hong ◽  
Shusen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Multiple Organ ◽  
Braf V600e ◽  
Case Presentation ◽  
Free Survival ◽  
Metastatic Lesions ◽  
Potential Prognostic Factor ◽  
New Mutations

<b><i>Background:</i></b> The B-Raf proto-oncogene (BRAF<sup>V600E</sup>) gene mutation has been identified in a variety of malignancies, but no evidence of the efficacy of vemurafenib treatment in BRAF<sup>V600E</sup> mutant breast cancer (BC) has been reported. <b><i>Case Presentation:</i></b> We reported a 60-year-old woman with confirmed triple-negative BC with BRAF<sup>V600E</sup> mutation. Progression-free survival (PFS) for first-line chemotherapy was 7 months. The patient received vemurafenib and albumin-bound paclitaxel as second-line therapy, exhibiting regression of some pulmonary metastatic lesions with concomitant progression of other lesions, and achieved 4.4 months of PFS. Genetic testing of the progressed pulmonary lesion revealed the BRAF<sup>V600E</sup> mutation, and acquired new mutations and AR amplification. The patient ultimately died of multiple organ failure and achieved 12 months of overall survival. <b><i>Conclusions:</i></b> The BRAF<sup>V600E</sup> mutation may be a potential prognostic factor and therapeutic target for BC.

scholarly journals High Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Breast Cancer: A Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Miao Zhang ◽  
Xuan-zhang Huang ◽  
Yong-xi Song ◽  
Peng Gao ◽  
Jing-xu Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Platelet To Lymphocyte Ratio ◽  
Free Survival ◽  
Node Negative ◽  
Lymphocyte Ratio

Background. We aimed to evaluate the correlation of platelet-to-lymphocyte ratio (PLR) with prognosis and clinicopathological characteristics of breast cancer. Methods. The PubMed and Embase databases were searched. Hazard ratio (HR) with 95% confidence interval (CI) was used to summarize disease-free survival (DFS) and overall survival (OS). Odds ratio (OR) was used to summarize tumor clinicopathological characteristics. Results. High PLR was associated with poor DFS and OS (DFS: HR = 1.47, 95% CI = 1.16–1.85, and Tau2 = 0.070; OS: HR = 1.88, 95% CI = 1.27–2.80, and Tau2 = 0.192). A Galbraith plot indicated that the studies by Allan et al. and Cihan et al. contributed the heterogeneity of DFS and OS, respectively. There were significant differences in the incidence of high PLR between stage II–IV and stage I groups (OR = 1.86, 95% CI = 1.20–2.90, and Tau2 < 0.001), between lymph node-positive and lymph node-negative groups (OR = 1.52, 95% CI = 1.22–1.91, and Tau2 =0.014), and between metastasis-positive and metastasis-negative groups (OR = 4.24, 95% CI = 2.73–6.59, and Tau2 < 0.001). Conclusions. Our results indicated that PLR was associated with poor prognosis of breast cancer and adequately predicted clinicopathological characteristics.

Metaplastic progression free survival compared to triple negative breast cancer, a retrospective analysis.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e12552-e12552
Author(s):  
Maryam B. Lustberg ◽  
Amanda Luff ◽  
Gregory S. Young ◽  
Rachel M. Layman ◽  
Ewa Mrozek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Analysis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Free Survival

scholarly journals Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Shengjie Sun ◽  
Huiyu Dong ◽  
Tao Yan ◽  
Junchen Li ◽  
Chao Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
Gynecological Cancer ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Poor Overall Survival ◽  
Free Survival ◽  
The Impact

Abstract Background Published studies present conflicting data regarding the impact of Thrombospondin-1 (TSP-1) expression on prognosis of various cancers . We performed this meta-analysis to clarify the preliminary predictive value of TSP-1. Methods Twenty-four studies with a total of 2379 patients were included. A comprehensive literature search was performed by using PubMed, Cochrane Library, Web of Science, Embase, and hand searches were also conducted of relevant bibliographies. Pooled hazard ratio s ( HRs ) with 95% confidence intervals ( CIs ) for patient survival and disease recurrence were initially identified to explore relationships between TSP-1 expression and patient prognosis. Results A total of 24 eligible studies were included in this meta-analysis. Our results showed that high level of TSP-1 was correlated significantly with poor overall survival ( OS ) (HR=1.40, 95% CI: 1.17~1.68). However, high TSP-1 expression predicted no significant impact on progression-free survival ( PFS )/ metastasis-free survival (MFS ) (HR=1.35, 95%CI: 0.87-2.10) and disease-free survival ( DFS )/ recurrence-free survival ( RFS ) (HR = 1.40, 95%CI: 0.77–2.53). In addition, we performed subgroup analyses which showed that high TSP-1 expression predicted poor prognosis in breast cancer and gynecological cancer. Conclusions Our findings indicated high TSP-1 expression may serve as a promising biomarker of poor prognosis and novel therapeutic target in cancers, especially in breast cancer and gynecological cancer.

scholarly journals Cis-Compound Mutations are Prevalent in Triple Negative Breast Cancer and Can Drive Tumor Progression

2016 ◽  
Author(s):  
Nao Hiranuma ◽  
Jie Liu ◽  
Chaozhong Song ◽  
Jacob Goldsmith ◽  
Michael Dorschner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
The Cancer Genome Atlas ◽  
Breast Cancers ◽  
Single Nucleotide Variants ◽  
Primary Tumors ◽  
Cancer Subtypes ◽  
Multiple Biopsies ◽  
Cancer Genome Atlas

About 16% of breast cancers fall into a clinically aggressive category designated triple negative (TNBC) due to a lack of ERBB2, estrogen receptor and progesterone receptor expression1-3. The mutational spectrum of TNBC has been characterized as part of The Cancer Genome Atlas (TCGA)4; however, snapshots of primary tumors cannot reveal the mechanisms by which TNBCs progress and spread. To address this limitation we initiated the Intensive Trial of OMics in Cancer (ITOMIC)-001, in which patients with metastatic TNBC undergo multiple biopsies over space and time5. Whole exome sequencing (WES) of 67 samples from 11 patients identified 426 genes containing multiple distinct single nucleotide variants (SNVs) within the same sample, instances we term Multiple SNVs affecting the Same Gene and Sample (MSSGS). We find that >90% of MSSGS result from cis-compound mutations (in which both SNVs affect the same allele), that MSSGS comprised of SNVs affecting adjacent nucleotides arise from single mutational events, and that most other MSSGS result from the sequential acquisition of SNVs. Some MSSGS drive cancer progression, as exemplified by a TNBC driven by FGFR2(S252W;Y375C). MSSGS are more prevalent in TNBC than other breast cancer subtypes and occur at higher-than-expected frequencies across TNBC samples within TCGA. MSSGS may denote genes that play as yet unrecognized roles in cancer progression.

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