Prognostic significance of MAGE-A10 and NY-ESO-1 cancer-testis antigen in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21126-e21126
Author(s):  
Tanja Badovinac Crnjevic ◽  
Jasminka Jakic Razumovic ◽  
Giulio C Spagnoli ◽  
Paula Podolski ◽  
Nera Saric ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Curative Surgery ◽  
Kaplan Meier ◽  
Expression Score ◽  
Cancer Testis

e21126 Background: Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors. In normal adult tissues CTA expression is restricted predominantly to germs cells of the adult testis and placenta. Based on their tumor-restricted expression pattern, CTAs are regarded as valuable targets for cancer immunotherapy. The prognostic significance of CTAs in breast cancer has not been analyzed previously. Methods: To evaluate the potential prognostic significance of two member of this family, MAGE-A10 and NY-ESO-1 antigens, we examined their expression in breast cancer patients who underwent curative surgery at our hospital between 2002 and 2003. Paraffin embedded tumor sections were collected retrospectively from 165 breast cancer patients and immunohistochemical staining for MAGE-A10 and NY-ESO-1 was performed. Impact of MAGE-A10 and NY-ESO-1 expression on disease free survival (DFS) and overall survival (OS) was analyzed by the Kaplan-Meier method using 8-year follow up data. Results: MAGE-A10 expression (score ≥2+) was detected in 105/164 (64%) and NY-ESO-1 expression (score ≥2+) was observed in 14/164 (8.5%) patients. 8-year DFS for MAGE-A10 positive patients was 69% and 73% for MAGE-A10 negative (p=0.452). 8-year OS for MAGE-A10 positive patients was 80% and 90% for MAGE-A10 negative (p=0.134). For NY-ESO-1 positive patients 8-year DFS was 67% and 70% for NY-ESO-1 negative patients (p=0.837). 8-year OS for NY-ESO-1 positive patients was 83% and 84% for NY-ESO-1 negative patients. (p=0.991) Conclusions: To our knowledge this is the first study analyzing prognostic significance CTAs in breast cancer. In this retrospective study we did not show statistically significant correlation between MAGE-A10 and NY-ESO-1 expression and clinical outcome. Additional studies are warranted to determine weather this antigens might have prognostic value in breast cancer patients.

Effect of mast cells on efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme b.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11522-11522
Author(s):  
Mark Wroblewski ◽  
Janna-Lisa Velthaus ◽  
Raimund Bauer ◽  
Volkmar Müller ◽  
Christian Schem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Granzyme B ◽  
Resistance Mechanism ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Kaplan Meier

11522 Background: Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. As mast cell (MC) density is known to correlate with tumor angiogenesis, we analyzed if inhibition of MC holds potential to increase efficacy of AAT in mice and cancer patients. Methods: C57BL/6J (WT), NSG or MC-deficient KitW-sh(Wsh) mice were subcutaneously injected with Panc02, EL4 or BxPC3 cells with or without bone marrow-derived MC. Tumors were treated with 20 mg/kg of anti-VEGFR2 antibodies (DC101) or 25 mg/kg cromoglicic acid. Tissue microarrays from n = 299 breast cancer patients from the GeparQuinto Phase 3 clinical trial were stained for MC and MC numbers were correlated with clinical data. Results: We observed that absence of MC reduced tumor growth and increased the efficacy of AAT in different tumor models. Intriguingly, AAT only initially reduced microvessel proliferation but this was abrogated over time as a result of MC-mediated resistance. We show that MC secrete increased amounts of granzyme b upon therapy, which mobilizes alternative pro-angiogenic factors from the tumor matrix. These factors act beside the targeted VEGFA-VEGFR2-axis and reinduce angiogenesis despite the presence of AAT. Importantly, MC-mediated resistance could be overcome using the FDA-approved MC inhibitor cromoglicic acid. In line with our preclinical data, high intratumoral MC density correlated with disease progression in HR+ breast cancer patients when Bevacizumab was added to standard neodjuvant chemotherapy (HR 8.45, p = 0.006). Accordingly, Kaplan-Meier curves indicated that disease free survival of patients with high tumoral MC density was numerically shorter in the whole cohort and significantly shorter in the HR+ cohort upon addition of AAT to chemotherapy (p = 0.168 and p = 0.004, respectively). Conclusions: Here we unravel a novel resistance mechanism, by which MC hamper efficacy of AAT in mice and cancer patients. In preclinical models this effect could be overcome by combining AAT with an FDA-approved MC inhibitor indicating high clinical relevance. Thus, combination of FDA-approved MC inhibitors with AAT might be a suitable approach to increase efficacy of AAT in the clinic.

scholarly journals Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort.

2020 ◽  
Author(s):  
Pooja Vaid ◽  
Anirudha Puntambekar ◽  
Rituja Banale ◽  
Ruhi Reddy ◽  
Rohini Unde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Therapy ◽  
Stromal Tumor ◽  
Breast Cancer Patients ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

Incidence and Prognostic Significance of Complete Axillary Downstaging After Primary Chemotherapy in Breast Cancer Patients With T1 to T3 Tumors and Cytologically Proven Axillary Metastatic Lymph Nodes

2002 ◽  
Vol 20 (5) ◽  
pp. 1304-1310 ◽  
Author(s):  
Roman Rouzier ◽  
Jean-Marc Extra ◽  
Jerzy Klijanienko ◽  
Marie-Christine Falcou ◽  
Bernard Asselain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Primary Chemotherapy ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.

Prognostic value of decrease on blood lymphocytes in breast cancer patients undergoing primary chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11537-e11537
Author(s):  
A. Vicente ◽  
E. García-Martínez ◽  
E. Gonzalez-Billalabeitia ◽  
M. Zafra ◽  
C. Castilla-Llorente ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Neoadjuvant Treatment ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Primary Chemotherapy ◽  
Tumor Control ◽  
Breast Cancer Patients ◽  
Blood Lymphocytes ◽  
Multivariant Analysis

e11537 Background: There is evidence about chemotherapy creating a better tumor control by inmune system. Neoadjuvant treatment is an excellent situation to study tumor behaviour. The aim of this study is to determine whether decreases on blood lymphocytes (BL) absolute number have a prognostic significance on women with breast cancer receiving primary chemotherapy (PC). Methods: A retrospective analysis was performed of 105 breast cancer patients who underwent PC. Doxorubicin (60mg/m2q3w) - Cyclophosphamide (600mg/m2q3w) x4c followed docetaxel (100 mg/m2q3w) x4c was PC regimen in 73,4%. We collected data on BL before the first cycle of PC (basal BL), just before second doxorubicin- cyclophosphamide (AC) cycle (BLa), and three weeks from the end of PC (BLb). The median decrease (MD) in blood lymphocytes has been calculated: MDa = BLa - basal BL; MDb = BLb - basal BL. Results: Of 105 patients with breast cancer 16,2% were clinical stage IIA, 19% IIB, 30,5% IIIA, 14,3% IIIB, 15,2% IIIC. The mean age was 50 years. The complete pathologic response (pCR) rate was 14,9% in primary tumor, and 37,9% in axillary nodes. The median follow up is 25 months (mo). Overall survival: (OS) 25,3 mo (range 4 - 89.3). Disease-free survival: (DFS) 21,8 mo (range 5 - 80.3). The median decrease on blood lymphocytes is MDa=300 106/L(2400, -1000), MDb=700 106/L(3900, -400). A decrease on BL just before second AC cycle (> MDa=300 106/L) is correlated with worse DFS, in univariant and multivariant analysis (HR =4.022; 95% CI:1.105–14.63; p 0.035 at first; HR=5.36; 95% CI:1.1–25.82; p 0.037 at former). Patients with BL decrease three weeks after finishing PC (>MDb=700 106/L) have worse DFS in univariant as multivariant analysis (HR=5.9 95% CI:1.2–27.5; p0.022 at first; HR=9.7 95% CI:1.11- 85.07; p 0.04 at former). We have not found significant differences in OS. Conclusions: A decrease on blood lymphocyte number in women with breast cancer undergoing primary chemotherapy is correlated with worse DFS. No significant financial relationships to disclose.

Primary outcome results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA505-LBA505 ◽  
Author(s):  
D. N. Krag ◽  
S. J. Anderson ◽  
T. B. Julian ◽  
A. Brown ◽  
S. P. Harlow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Regional Control ◽  
Kaplan Meier ◽  
Regional Node ◽  
Group 2 ◽  
Group 1

LBA505 Background: NSABP B-32 is the largest prospective randomized phase III trial designed to determine in SN negative patients that SNR alone results in the same survival and regional control as SNR + AD while reducing morbidity. It was designed to detect a survival difference of 2% between the 2 groups at 5 years. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group 1) or to SNR alone with AD only if SNs were positive (Group 2). 3,989 (71.1%) of the 5,611 patients were SN negative and followed for events. 99.9% of these SN negative patients had follow-up information: 1,975 in Group 1 and 2,011 in Group 2. Median time on study was 95.3 months. Patients were well balanced across clinical strata. Log-rank tests for unadjusted analyses and Cox proportional hazard models adjusting for study stratification variables were used to compare overall survival (OS) and disease-free survival (DFS) between the two groups. Two-sided p-values were used. HR values > 1 indicate a more favorable outcome in Group 1 (SNR + AD). Results: Comparisons of OS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.20 (p = 0.12) and an adjusted HR of 1.19 (p=0.13). Five-year Kaplan-Meier estimates for OS are 96.4% in Group 1 and 95.0% in Group 2 and the 8-year estimates are 91.8% and 90.3%, respectively. Comparisons of DFS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.05 (p=0.54) and an adjusted HR of1.07 (p=0.57). No substantial differences could be seen across sites for first treatment failure. Five-year Kaplan-Meier estimates for DFS are 89.0% in Group 1, and 88.6% in Group 2 and the 8-year estimates are 82.4% and 81.5%, respectively. Local and Regional Recurrences: There were 54 local recurrences in Group 1 and 49 in Group 2 (p=0.55). There were 8 regional node recurrences as first events in Group 1 and 14 in Group 2 (p=0.22). Conclusions: No significant differences were observed in OS, DFS, or regional control between the trial groups. Within the limits of this trial, SNR without AD is validated as a safe and effective method for regional node treatment of SN negative breast cancer patients. [Table: see text]

scholarly journals Prognostic significance of preoperative serum inflammation markers in patients with male breast cancer

2021 ◽  
Author(s):  
Xing Li ◽  
Zhengchong Xiong ◽  
Jin Wang ◽  
Juan Fu ◽  
Xinhua Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Male Breast Cancer ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Male Breast ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Inflammation Markers ◽  
Lymphocyte Ratio

Abstract BackgroundThere were no predictive prognosis factors of serum in male breast cancer, while breast cancer is a heterogeneous disease. The purpose of our study was to determine the prognostic implications of the pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) in the serum of patients with male breast cancer. Methods：We retrospectively identified an random cohort of male breast cancer patients treated at the Sun Yat-Sen University Cancer Center between Jan1, 1996 and Dec31, 2016. A number of 108 patients had a different inflammation markers recorded pre-operation. Survival status was retrieved from our cancer center registry and phone follow-up. Cox proportional hazards regression model were used to analyze the disease-free survival (DFS) and overall survival (OS). Results：Among these patients in this study, 13 (12%) had disease recurrence, and 7 (6.5%) patients appeared distant metastasis. No statistically significant association of the preoperative NLR, PLR or LMR level with patients’ different outcomes was found. Conclusions: In short, we were unable to establish a connection between preoperative inflammation biomarkers and male breast cancer patients’ survival. Neither NLR, PLR nor LMR is useful for predicting prognosis in male breast cancer patients, and prospective studies to evaluate the above biomarkers as a simple prognostic trail is necessary.

scholarly journals The Prognostic Significance of Anisomycin-Activated Phospho-c-Jun NH2-Terminal Kinase (p-JNK) in Predicting Breast Cancer Patients’ Survival Time

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Chen ◽  
Xuantong Zhou ◽  
Xiangyi Kong ◽  
Zhaohui Su ◽  
Xiangyu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Breast Cancer Cell Lines ◽  
Rank Test ◽  
Significant Prognostic Factor ◽  
Breast Cancer Patients

This study aims to investigate the prognostic significance of p-JNK in breast cancer patients receiving neoadjuvant chemotherapy (NACT) and analyze the relationship between anisomycin, p-JNK. A total of 104 breast cancer patients had NACT were enrolled in this study. The western blot and immunohistochemistry assays were used to determine the protein expressions of p-JNK in human breast cancer cell lines and patients’ cancer tissues. The chi-square test and Fisher’s exact test were adopted to gauge the associations between breast cancer and clinicopathological variables by p-JNK expression, whereas the univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of p-JNK expression. The Kaplan-Meier plots and the log-rank test were adopted to determine patients’ disease-free survival (DFS) and overall survival (OS). Findings indicated that the p-JNK expression had prognostic significance in univariate and multivariate Cox regression survival analyses. Results of log-rank methods showed that: (1) the mean DFS and OS times in patients with high p-JNK expression were significantly longer than those in patients with low p-JNK expression (χ2 = 5.908, P = 0.015 and χ2 = 6.593, P = 0.010, respectively). p-JNK expression is a significant prognostic factor that can effectively predict the survival in breast cancer patients receiving NACT. Treatment with the JNK agonist anisomycin can induce apoptosis, lead to increased p-JNK expression and decreased p-STAT3 expression. Moreover, the p-JNK expression was inversely correlated with p-STAT3 expression.

The Favorable Prognostic Significance of Surgery-Induced Hyperprolactinemia in Node-Positive Breast Cancer Patients: Ten-Year Disease-Free Survival Results

2005 ◽  
Vol 20 (1) ◽  
pp. 60-64 ◽  
Author(s):  
A. Bignami ◽  
P. Lissoni ◽  
F. Brivio ◽  
F. Galbiati ◽  
S. Pescia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Prolactin Secretion ◽  
Axillary Node ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Negative Breast Cancer ◽  
Node Involvement

It has been shown that each manipulation of the mammary region, including breast surgery, may stimulate prolactin secretion. However, it has also been observed that in more than 50% of breast cancer patients surgical removal of the tumor is not followed by enhanced prolactin secretion. This might be indicative of an altered psychoneuroendocrine control of the mammary gland, which could lead to the onset of more biologically aggressive breast cancer. In fact, surgery-induced hyperprolactinemia has been proven to be associated with a better prognosis in terms of survival in node-negative breast cancer patients. The present study was performed to investigate the impact of postoperative hyperprolactinemia on the disease-free survival (DFS) of breast cancer patients with axillary node involvement. The study included 100 consecutive node-positive breast cancer patients who were followed for at least 10 years. Surgery-induced hyperprolactinemia occurred in 45/100 (45%) patients without any significant correlation with the main prognostic variables including number of involved nodes and ER status. The two groups of patients received the same adjuvant therapies. After a median follow-up of 151 months, the recurrence rate in patients with surgery-induced hyperprolactinemia was significantly lower than in patients with no postoperative hyperprolactinemia (23/45 vs 43/55, p<0.01). Moreover, DFS was significantly longer in hyperprolactinemic patients than in patients who had no enhanced secretion of prolactin postoperatively. In agreement with the results described previously in node-negative breast cancer, our study demonstrates the favorable prognostic significance of surgery-induced hyperprolactinemia in terms of DFS duration also in breast cancer patients with axillary node involvement, independent of the other well-known prognostic variables, thereby confirming that the psychoneuroendocrine status of cancer patients may influence the prognosis of their disease.

Prognostic Significance of GRP78 Expression Patterns in Breast Cancer Patients Receiving Adjuvant Chemotherapy

2011 ◽  
Vol 26 (3) ◽  
pp. 188-196 ◽  
Author(s):  
Mauricio Z. Baptista ◽  
Luis Otavio Sarian ◽  
José Vassallo ◽  
Glauce A. Pinto ◽  
Fernando A. Soares ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Adjuvant Chemotherapy ◽  
Cell Membrane ◽  
Cancer Patients ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Significant Difference

This study examined the associations between GRP78 expression and breast cancer recurrence and survival in patients treated with anthracyclines in the adjuvant setting. GRP78 expression was assessed in 106 stage II/III breast cancer patients. Tissue microarray was used to perform immunohistochemistry and to determine the GRP78 expression in endoplasmic reticulum and cell membrane of breast tumors. Four distinct scenarios (low and high thresholds) were developed. For high thresholds, 16% and 40% of our cases were GRP78-positive for endoplasmic reticulum and cell membrane, respectively. For low thresholds, 74% and 87% of our cases were GRP78-positive for endoplasmic reticulum and cell membrane, respectively. In the endoplasmic reticulum high-threshold scenario, GRP78 positive was found to be significantly frequent in T3 tumors (p=0.02), and inversely related to ERBB2 overexpression (p=0.03). There was a lower proportion of GRP78-positive cases among women between 50 and 65 years of age (p=0.02). In the endoplasmic reticulum low-threshold scenario, the proportion of GRP78-positive cases was significantly higher in women younger than 50 years and in those who were premenopausal (p=0.04). No statistically significant difference was found in survival probabilities among the scenarios examined. In our cohort, GRP78 overexpression was not a predictor of overall or disease-free survival of patients receiving anthracycline-based adjuvant chemotherapy.

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