Limited impact of tamoxifen following dose-intensive L-FAC multimodality therapy of breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10741-10741
Author(s):  
K. W. Jabboury ◽  
A. Wong ◽  
K. Sexton ◽  
L. Rogers ◽  
K. King ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Dose Intensity ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Who Grade ◽  
Free Survival ◽  
Hand Foot Syndrome ◽  
The Impact ◽  
Grade Iii

10741 Background: Front-line dose-intensive L-FAC has demonstrated a favorable 5-year relapse free survival pattern (ASCO 2004 #739). Tamoxifen was given for 5 years to ER+ patients after L-FAC completion. We evaluated the impact of adding tamoxifen to L-FAC. By design, this pilot study excluded low-risk patients not candidates for chemotherapy. Methods: 109 breast cancer patients were enrolled (4 excluded due to treatment violations) from 6/1989 to 1/2003: 20 Stage I (S), 52 S-II, 22 S-III, for a total of 94 patients. 11 S-IV patients were excluded from survival analysis. Adverse tumor presentations included: ER- 49, PgR- 60, P53+ 24, non-diploid 39, histological grade III 37, CerbB2+ 33. L-FAC included 72 hour (h) iv infusion 400mg/m2/day (d) 5-fluorouracil (F) modulated by iv bolus 200mg/m2/d X3 leucovorin (L), concomitantly with 24h iv d1 600–1000mg/m2 cyclophosphamide (C), 48h iv d2 + d3 60mg/m2 doxorubicin (A). S-I and S-II were given 6 courses and 8 for S-III. Increasing A + C dose level and/or shortening treatment intervals < 3 weeks with growth factors provided intensification. 40 patients received tamoxifen. Results: At a median follow-up of 74 months (range 9–214), 73 (78%) are alive (1 with relapse). Relapse free survival was: S-I 95%, S-II 81%, S-III 78%. At average course intervals of 18 days, dose intensity A/C mg/m2/wk was 24.2 / 335.4 with evidence of WHO grade III/IV stomatitis in 43%, neutropenia 59%, cumulative thrombocytopenia 50%, hand-foot syndrome 32% of patients. Aside from delayed relapse associated with tamoxifen, relapse-free survival >82 months was similar with and without tamoxifen. No relapse was observed after >53 months in ER- tumors despite showing higher frequency of adverse tumor risk factors. Conclusion: The impact of adding tamoxifen appears quite limited in a patient population with adverse tumor presentation treated with dose-intensive L-FAC. No significant financial relationships to disclose.

scholarly journals Prognostic impact of the glypican family of heparan sulfate proteoglycans on the survival of breast cancer patients

2021 ◽  
Author(s):  
Paulina Karin Grillo ◽  
Balázs Győrffy ◽  
Martin Götte
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Heparan Sulfate ◽  
Cancer Patients ◽  
Heparan Sulfate Proteoglycans ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
The Impact

Abstract Purpose Dysregulated expression of proteoglycans influences the outcome and progression of numerous cancers. Several studies have investigated the role of individual glypicans in cancer, however, the impact of the whole glypican family of heparan sulfate proteoglycans on prognosis of a large patient cohort of breast cancer patients has not yet been investigated. In the present study, our aim was to investigate the prognostic power of the glypicans in breast cancer patients. Methods We used a public database including both gene expression data and survival information for 3951 breast cancer patients to determine the prognostic value of glypicans on relapse-free survival using Cox regression analysis. Moreover, we performed quantitative Real-Time PCR to determine glypican gene expression levels in seven representative breast cancer cell lines. Results We found that high GPC3 levels were associated with a better prognosis in overall breast cancer patients. When stratified by hormone receptor status, we found that in worse prognosis subtypes low GPC1 levels correlate with a longer relapse-free survival, and in more favorable subtypes low GPC6 was associated with longer survival. Conclusion Our study concludes that glypicans could act as subtype-specific biomarkers for the prognosis of breast cancer patients and sparks hope for future research on glypicans possibly eventually providing targets for the treatment of the disease.

scholarly journals Risk factors for pegylated liposomal doxorubicin-induced moderate to severe hand-foot syndrome in breast cancer patients: assessment of baseline clinical parameters

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guohua Liang ◽  
Wenjie Ma ◽  
Yanfang Zhao ◽  
Eryu Liu ◽  
Xiaoyu Shan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Prediction Model ◽  
Cancer Patients ◽  
Blood Circulation ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
Breast Cancer Patients ◽  
Hand Foot Syndrome ◽  
Peripheral Blood Circulation

Abstract Background Hand-foot syndrome (HFS) is a side effect of skin related to pegylated liposomal doxorubicin (PLD) application. Moderate to severe hand-foot syndrome (MSHFS) might have a serious impact on patients’ quality of life and treatment. However, information on risk factors for the development of MSHFS is still limited. To analyze the risk factors for PLD-induced MSHFS in breast cancer patients and constructed a logistic regression prediction model. Methods We conducted a retrospective analysis of breast cancer patients who were treated with a PLD regimen in the Tumor Hospital of Harbin Medical University from January 2017 to August 2019. A total of 26 factors were collected from electronic medical records. Patients were divided into MSHFS (HFS > grade 1) and NMHFS (HFS ≤ grade 1) groups according to the NCI classification. Statistical analysis of these factors and the construction of a logistic regression prediction model based on risk factors. Results A total of 44.7% (206/461) of patients developed MSHFS. The BMI, dose intensity, and baseline Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels in the MSHFS group, as well as good peripheral blood circulation, excessive sweat excretion, history of gallstones, and tumour- and HER2-positive percentages, were all higher than those in the NMHFS group (P < 0.05). The model for predicting the occurrence of MSHFS was P = 1/1 + exp. (11.138–0.110*BMI-0.234*dose intensity-0.018*baseline ALT+ 0.025*baseline AST-1.225*gallstone history-0.681* peripheral blood circulation-1.073*sweat excretion-0.364*with or without tumor-0.680*HER-2). The accuracy of the model was 72.5%, AUC = 0.791, and Hosmer-Lemeshow fit test P = 0.114 > 0.05. Conclusions Nearly half of the patients developed MSHFS. The constructed prediction model may be valuable for predicting the occurrence of MSHFS in patients.

scholarly journals Immunohistochemical analysis of CD155 expression in triple-negative breast cancer patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253176
Author(s):  
Katsuhiro Yoshikawa ◽  
Mitsuaki Ishida ◽  
Hirotsugu Yanai ◽  
Koji Tsuta ◽  
Mitsugu Sekimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Tumor Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Histological Grade ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Antitumor Immunotherapy

Introduction CD155 is an immune checkpoint protein. Its overexpression is an indicator of poor prognosis in some types of cancer. However, the significance of CD155 expression in patients with triple-negative breast cancer, and the relationship between CD155 and programmed death-ligand 1 (PD-L1) expression, have not yet been analyzed in detail. Methods Using immunohistochemical staining and tissue microarrays, we analyzed the expression profiles of CD155 and PD-L1 in 61 patients with triple-negative breast cancer. Relapse-free survival and overall survival rates were compared according to CD155 expression. The correlation between CD155 expression and clinicopathological factors, including PD-L1 expression (using SP142 and 73–10 assays), was also examined. Results CD155 expression was noted in 25 patients (41.0%) in this cohort. CD155 expression did not correlate with pathological stage, histological grade, Ki-67 labeling index, or stromal tumor-infiltrating lymphocytes. Only PD-L1 expression in tumor cells by SP142 assay significantly correlated with CD155 expression (p = 0.035); however, PD-L1 expression in tumor cells by 73–10 assay did not show a correlation (p = 0.115). Using the 73–10 assay, 59% of patients showed CD155 and/or PD-L1 expression in tumor cells. Moreover, using the SP142 assay, 63.3% of patients showed CD155 and/or PD-L1 expression in immune cells. CD155 expression did not correlate with either relapse-free survival or overall survival (p = 0.485 and 0.843, respectively). Conclusions CD155 may be a novel target for antitumor immunotherapy. The results of this study indicate that CD155 may expand the pool of candidates with triple-negative breast cancer who could benefit from antitumor immunotherapy.

Impact of chemotherapy dose-related factors on survival in breast cancer patients treated with adjuvant anthracycline-based chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 668-668 ◽  
Author(s):  
I. Chirivella ◽  
B. Bermejo ◽  
A. Insa ◽  
A. Perez-Fidalgo ◽  
A. Magro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Negative Impact ◽  
Histological Grade ◽  
Menopausal Status ◽  
Dose Intensity ◽  
Disease Stage ◽  
Related Factors ◽  
Ct Dose ◽  
The Impact

668 Background: The relationship between chemotherapy (CT) dose intensity and patient (pt) outcome in the management of early stage breast cancer (EBC) is still controversial. Although randomised clinical trials have provided evidence that supports the delivery of full standard doses of CT on schedule, precise thresholds for CT dose-related factors and their impact on survival-related endpoints have not yet been fully defined. The objective of this project is to assess the impact of CT dose-related factors on event-free and overall survival in a large group of EBC pts treated with anthracycline-based chemotherapy. Methods: A total of 1056 EBC (stage I-II-IIIA) cases diagnosed and treated from January 1980 to December 2000 were retrospectively studied. All of them received adjuvant anthracycline non-taxanes-based CT. Consecutive charts from 793 pts that were fully completed were included in the analysis. Survival-related endpoints were analysed through Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards models. Results: With a median follow-up of 10.0 years, pts exposed to either > 2 cycle-delay (delay at any cycle defined as ≥ 3 days vs. plan), or ≥ 15 day-delay across the whole CT regimen, or < 95% relative dose intensity (RDI) showed significantly worse 10-year Event-Free Survival (EFS) and Overall Survival (OS) as compared to pts with no dose delay/reduction (data shown below). Controlling for age at diagnosis, disease stage, histological grade, menopausal status and year of treatment did not modify these results. Conclusions: Based on this preliminary analysis, CT dose delays and reductions in EBC pts treated with adjuvant anthracycline-based regimens have a significantly negative impact on EFS and OS. [Table: see text] No significant financial relationships to disclose.

Prognostic significance of immunohistochemical expression of Rb gene product in operable breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21121-21121
Author(s):  
H. Song ◽  
Y. Do ◽  
S. Gang ◽  
S. Kwon ◽  
S. Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Gene Product ◽  
Prognostic Significance ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Node Metastasis ◽  
Rb Gene

21121 Background: The aim of this study was to investigate the prognostic significance of the expression of Rb gene product in operable invasive breast cancer by performing immunohistochemical analysis. Methods: Between January 1993 and December 2001, 212 operable invasive breast cancer patients underwent immunohistochemical staining for Rb, and we retrospectively analyzed these results together with the clinical outcomes. Results: The overexpression of p53 was detected in 72.7% of the cases. The overexpression of Rb was correlated with positive hormonal receptor (p=0.000), and inversely correlated with lymph node metastasis (p=0.017) and vascular invasion (p=0.004). The tumor size, tumor histology, histologic grade, and tumor stage were not related to the overexpression of p53. Multivariate Cox regression analysis indicate that lymph node metastasis and tumor size were the significant prognostic factors for overall survival; lymph node metastasis was the significant prognostic factor for relapse free survival. On the subgroup analysis, the Rb expressors showed better 7-year overall survival (98.5% vs. 81.5%, respectively, p=0.005) and relapse free survival (94.1% vs. 77.4%, respectively, p=0.021) than did the p53 non-overexpressors for the patients without lymph node metastasis. However, for the patients with lymph node metastasis, the survival rates were not different for both the Rb expressors and the Rb non-expressors. Conclusions: Immunohistochemical staining of the Rb gene product was an independent prognostic factor for predicting survival of the lymph node negative operable breast cancer patients. No significant financial relationships to disclose.

Involvement of NK cell molecular signatures in favorable prognosis of breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10565-10565
Author(s):  
Maria Libera Ascierto ◽  
Michael O Idowu ◽  
Yingdong Zhao ◽  
Davide Bedognetti ◽  
Paolo Antonio Ascierto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Nk Cells ◽  
Cancer Patients ◽  
Adhesion Molecules ◽  
Nk Cell ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Activating Receptors

10565 Background: Tumor cell recognition by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with their ligands expressed on tumor cells. In addition, NK cells express adhesion molecules that facilitate formation of the immunological synapse with the tumor targets. Here, we investigated whether the coordinate expression of NK activating receptors and adhesion molecules could provide a signature to segregate breast cancer patients into relapse and relapse-free outcomes. Methods: Gene expression profiling, RT-PCR screening and survival analysis were performed on RNA extracted from primary breast cancers. Tumors were obtained from patients experiencing either 5-8 years relapse-free survival or tumor relapse within 1-3 years following initial treatment. Results: Tumors from patients with a favorable prognosis were characterized by increased expression of genes involved in NK cell interaction with tumor cells and its activation signaling. In particular, up-regulation of Natural Cytotoxicity Receptors (NCRs), leukocyte function-associated antigen 1 (LFA-1), CD226 (DNAM-1) and CD96 was observed in relapse-free patients. Thus, the expression of the NK activating receptors and relevant adhesion molecules involved in NK cell:target interactions can predict relapse free survival in breast cancer patients. Conclusions: Results from the present study, highlighted the effector cooperation between the innate and adaptive immune components within the tumor microenvironment. The NK cells parameters identified in this study, together with the prognostic B and T cell signatures previously reported by us, represent a powerful tool for predicting breast cancer outcome which might be easily introduced in clinical practice.

Dose-Dense Anthracycline-Based Chemotherapy for Node-Positive Breast Cancer

2002 ◽  
Vol 20 (17) ◽  
pp. 3637-3643 ◽  
Author(s):  
Georgiana K. Ellis ◽  
Robert B. Livingston ◽  
Julie R. Gralow ◽  
Stephanie J. Green ◽  
Tove Thompson
Keyword(s):  
Breast Cancer ◽  
Dose Intensity ◽  
Free Survival ◽  
Node Positive ◽  
Hand Foot Syndrome ◽  
Continuous Dose ◽  
Standard Doxorubicin ◽  
Her 2 ◽  
Dose Dense ◽  
Theoretical Considerations

PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor–negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m2. Cyclophosphamide 60 mg/m2 was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m2/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m2/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with “standard” doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.

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