Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years)

2020 ◽  
pp. 1-10
Author(s):  
Maja Sirotković-Skerlev ◽  
Natalija Dedić Plavetić ◽  
Filip Sedlić ◽  
Sanja Kusačić Kuna ◽  
Damir Vrbanec ◽  
...  

BACKGROUND: Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis. OBJECTIVE: This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness. METHODS: Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty individuals without malignancy. RESULTS: Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200 U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters. CONCLUSIONS: Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up.

1982 ◽  
Vol 68 (6) ◽  
pp. 477-480 ◽  
Author(s):  
Andrea Veronesi ◽  
Renato Talamini ◽  
Serenella Longhi ◽  
Diana Crivellari ◽  
Enzo Galligioni ◽  
...  

Carcinoembryonic antigen (CEA) assays (2536) were performed in 380 disease-free breast cancer patients after radical mastectomy. In the 334 evaluable patients with 3 or more determinations, the overall relapse rate after a median follow-up of 29 months was 11 %. Of 203 patients with normal CEA values, 19 (9.3 %) relapsed. In the 50 patients with the highest CEA value greater than 20 ng/ml, the relapse rate was 26 %; in the 12 patients with gradually increasing CEA elevations it was 50 %. However, CEA was unable to predict recurrence in N- patients. Premastectomy N+ was significantly associated with greater than 20 ng/ml or gradually increasing CEA values, suggesting the lack of an independent prognostic value of CEA in our patient population.


1995 ◽  
Vol 10 (1) ◽  
pp. 24-29 ◽  
Author(s):  
L. Rodríguez De Paterna ◽  
F. Arnaiz ◽  
J. Estenoz ◽  
B. Ortuño ◽  
E. Lanzós

Serum levels of CEA, CA 15.3 and CA 27.29 were measured during the follow-up of 499 breast cancer patients. Studies included three different groups of women: 82 blood donors free of disease, 42 patients with non-malignant breast diseases and 499 breast cancer patients. After the determinaion of cut-off values, serum levels of tumor markers did not show significant elevations in benign breast diseases. On the basis of our results CA 15.3 (sensitivity = 57%; accuracy = 87%) was the most effective marker, CA 27.29 (sensitivity = 62%; accuracy = 83%) was the most sensitive and CEA (sensitivity = 45%; accuracy = 81%) was the least sensitive and effective marker. The combined use of markers was evaluated by step-wise logistic regression analysis. The regression coefficients showed that CA 15.3 (coeff. = 2.97) and CA 27.29 (coeff. = 1.46) were suitable for the detection of possible metastases during follow-up. Finally, we studied the relationship between pT, pN, pM and circulating levels of CA 15.3 and CA 27.29.


2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 67-67 ◽  
Author(s):  
Joaquina Martínez-Galán ◽  
Blanca Torres-Torres ◽  
Jesús Soberino ◽  
Sandra Ríos ◽  
Cynthia S. González Rivas ◽  
...  

67 Background: Objective of this study was to determine the concordance of promoter methylation of 14-3-3σ and ESR1 in circulating DNA of breast cancer patients with response and their association with clinicopathological parameters and disease prognosis. Methods: Plasmawas sampled prospectively from 110 patients diagnosed of breast cancer. A PCR quantitative technique was used to analyze the utility of circulating DNA with CpG island hypermethylation of ESR1, 14-3-3σ, Rar-B and APC genes promoter regions as breast cancer biomarkers. Results: The cutoff points for the genes methylated promoters were established from the ROC curves, selecting values that gave the maximal likelihood ratio. Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179); and presence of methylated 14-3-3σ was associated with T3-4 stage (p<0.05) and nodal positive status (p<0.05). Mean serum values of methylated genes before treatment was for ESR1:0.009µg/ml, 14-3-3σ:0.047µg/ml, Rar B:0.0001µg/ml and APC:0.012µg/ml. Mean serum values of methylated genes after treatment was for ESR1:0.003 µg/ml, 14-3-3σ:0.038µg/ml, Rar-B:0 µg/ml and APC:0.001µg/ml. In the light of the discriminatory power of ESR1 and 14-3-3σ and the finding that serum levels of methylated gene promoters changed after breast cancer treatment, post-treatment modifications in these two promoters were analyzed. We observed lower methylated ERS1,14-3-3-σ and APC values after surgery, respect pretreatment levels, but without an overall statistically significant difference.With a median follow-up of 8 years, we found that patients with a significant decrease of sera methylated levels of these genes after surgery had better time to progression an overall survival respect patients without this observation. Conclusions: These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation of specific gene promoters in DNA extracted from serum. Although numerous issues remain to be resolved, the quantitative measurement of circulating methylated DNA is a promising tool for cancer prognostic assessment.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12017-e12017
Author(s):  
D. Sener Dede ◽  
S. Aksoy ◽  
N. Bulut ◽  
O. Dizdar ◽  
Z. Arik ◽  
...  

e12017 Background: Cancer antigen 15–3 (CA 15–3) and carcinoembryonic antigen (CEA), are often used in follow up care of breast cancer and provide important clues to the clinicians for disease progression in metastatic and recurrent breast cancer. Triple-negative breast cancers are frequently defined as a single group identifiable using routine clinical tests. They are negative for estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), the so-called triple-negative breast cancers. In this study we compared the tumor markers of triple negative breast cancer and non-triple negative patients. Methods: We retrospectively analyzed serum CEA and CA 15–3 levels of both triple negative and non-triple negative breast cancer patients at the time of first diagnosis and when they developed metastatic disease. Results: 544 consecutive nonmetastatic breast cancer patients presenting at Hacettepe University Institute of Oncology, Ankara, Turkey, with a median age of 49 were evaluated. 15.1% of the patients were triple negative breast cancer. At the time of diagnosis triple negative group had lower serum CEA (2.5 ± 5.9 vs 4.0 ±16.4 p = 0.35) and CA 15–3 (23.7 ± 14.6 vs 37.1 ± 117; p = 0.021) levels compared to non-triple negative group. In patients who developed metastasis during follow up; the CEA (3.2 ± 3.8 vs 29.6 ± 106.4 p = 0.022) and CA15–3 (46.9 ± 46.3 vs 203.2 ± 534 p = 0.008) levels were also significantly lower in triple negative breast cancer group compared to non-triple negative group.In non-triple negative breast cancer patients who developed metastasis, mean serum levels of CEA and CA15–3 significantly increased compared to baseline, whereas in triple negative group who developed metastasis CEA and CA 15–3 levels did not differ significantly. Conclusions: While being a good laboratory parameter in the follow-up of patients with breast cancer metastases, tumor markers may not show the increased tumor burden in the triple-negative breast cancer patients. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22182-e22182
Author(s):  
Mary Ann Kosir ◽  
Donghong Ju

e22182 Background: The chemokine CXCL7 is associated with tumor migration, invasion and angiogenesis and is a ligand for CXCR2. The purpose of the study is to measure changes in serum chemokine CXCL7 from resectable breast cancer patients between preoperative and postoperative blood samples. Methods: With IRB approval, we prospectively collected serum samples from patients undergoing breast cancer surgery immediately preoperatively and at least one week postoperatively. Serum CXCL7 protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using human CXCL7/NAP-2 Duo set ELISA Development System (R and D Systems, Minneapolis, MN) according to manufacturer’s instructions. Measurements were performed in duplicate with three separate experiments. Results were analyzed using unpaired and paired Student’s t-Test. Demographic and clinical information were collected. Normal donor samples were from ProteoGenex. Results: Twenty-three matched serum samples were analyzed. The mean age was 52 years (range 36-67), 65.2% were African American, 56.5% underwent partial mastectomy. There were 5 in Stage I, 9 in Stage II, 2 in Stage III, and 7 in Stage 0. Only 4 of 16 with invasive cancer had nodal disease, 11 were ER positive, 6 were triple negative, and 5 of 7 with DCIS were ER positive. Matched serum samples showed greater CXCL7 serum levels in preoperative samples when compared to normal donor samples (9.10 ±0.45 vs 8.10 ± 0.22 ug/ml; mean±sem, p<0.05). The CXCL7 serum levels were significantly decreased in postoperative serum as compared to preoperative serum (8.40 ± 0.47 vs 9.10 ± 0.45 ug/ml; mean±sem, p<0.05) reaching normal donor serum levels. When individual matched pairs of serum were analyzed, 16 showed decrease in postoperative CXCL7 levels compared to preoperative. Conclusions: The chemokine CXCL7 found in serum is increased in breast cancer patients compared to normal donors, and significantly decreases postoperatively to normal levels. This supports translational research of the role of CXCL7 in breast cancer.


1990 ◽  
Vol 45 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Anne M. Uyterlinde ◽  
Jan P. A. Baak ◽  
Nellie W. Schipper ◽  
Hans Peterse ◽  
Erna Matze ◽  
...  

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