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.

scholarly journals SLC6A8-mediated intracellular creatine accumulation enhances hypoxic breast cancer cell survival via ameliorating oxidative stress

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Qiao Li ◽  
Manran Liu ◽  
Yan Sun ◽  
Ting Jin ◽  
Pengpeng Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Histological Grade ◽  
Metabolic Adaptation ◽  
Mitochondrial Activity ◽  
Cell Viability Assay ◽  
Ki 67 ◽  
The Impact

Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with poor prognosis and limited treatment options. Hypoxia is a key hallmark of TNBC. Metabolic adaptation promotes progression of TNBC cells that are located within the hypoxic tumor regions. However, it is not well understood regarding the precise molecular mechanisms underlying the regulation of metabolic adaptions by hypoxia. Methods RNA sequencing was performed to analyze the gene expression profiles in MDA-MB-231 cell line (20% O2 and 1% O2). Expressions of Slc6a8, which encodes the creatine transporter protein, were detected in breast cancer cells and tissues by quantitative real-time PCR. Immunohistochemistry was performed to detect SLC6A8 protein abundances in tumor tissues. Clinicopathologic correlation and overall survival were evaluated by chi-square test and Kaplan-Meier analysis, respectively. Cell viability assay and flow cytometry analysis with Annexin V/PI double staining were performed to investigate the impact of SLC6A8-mediated uptake of creatine on viability of hypoxic TNBC cells. TNBC orthotopic mouse model was used to evaluate the effects of creatine in vivo. Results SLC6A8 was aberrantly upregulated in TNBC cells in hypoxia. SLC6A8 was drastically overexpressed in TNBC tissues and its level was tightly associated with advanced TNM stage, higher histological grade and worse overall survival of TNBC patients. We found that SLC6A8 was transcriptionally upregulated by p65/NF-κB and mediated accumulation of intracellular creatine in hypoxia. SLC6A8-mediated accumulation of creatine promoted survival and suppressed apoptosis via maintaining redox homeostasis in hypoxic TNBC cells. Furthermore, creatine was required to facilitate tumor growth in xenograft mouse models. Mechanistically, intracellular creatine bolstered cell antioxidant defense by reducing mitochondrial activity and oxygen consumption rates to reduce accumulation of intracellular reactive oxygen species, ultimately activating AKT-ERK signaling, the activation of which protected the viability of hypoxic TNBC cells via mediating the upregulation of Ki-67 and Bcl-2, and the downregulation of Bax and cleaved Caspase-3. Conclusions Our study indicates that SLC6A8-mediated creatine accumulation plays an important role in promoting TNBC progression, and may provide a potential therapeutic strategy option for treatment of SLC6A8 high expressed TNBC.

Occurrence of BRCA1–2 mutations and overall survival among breast cancer patients from Sardinia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22215-e22215
Author(s):  
G. Palmieri ◽  
G. Palomba ◽  
A. Loi ◽  
A. Uras ◽  
M. Budroni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Geographical Distribution ◽  
Germline Mutations ◽  
Disease Stage ◽  
Breast Cancer Patients ◽  
Sardinian Population ◽  
Incident Cases ◽  
The Impact

e22215 Background: Germline mutations in BRCA1-2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA1–2 mutations on prognosis and survival of breast cancer patients is still debated. In this study, we extensively investigated the prevalence and geographical distribution of BRCA1–2 mutations in the entire genetically-homogeneous Sardinian population as well as tried to clarify the influence of such mutations on breast cancer-specific survival. Methods: Among incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA1–2 mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan- Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis. Results: A lower breast cancer-specific overall survival rate was observed in BRCA1–2 mutation-positive patients after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets. The geographical distribution of BRCA1–2 mutations was related to specific three large areas of Sardinia: a) the northern area, linguistically different from the rest of the island (where a BRCA2–8765delAG mutation with founder effect was predominant); b) the central-eastern area, land of the ancient Sardinian population (where BRCA2 mutations are still largely more common thanBRCA1 mutations); and c) the south-western area, with many Phoenician and Carthaginian locations (where BRCA1 mutations are prevalent). Conclusions: In Sardinian breast cancer population, the effects of BRCA1–2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA1–2 mutation carriers and non-carriers. Finally, we identified some probands' phenotypic features which may be predictive for the presence of BRCA1–2 germline mutations and should be therefore considered when counselling patients about undergoing genetic testing. No significant financial relationships to disclose.

scholarly journals Evaluating the impact of relative total dose intensity (RTDI) on patient's short- and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer: A pooled analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1065-1065
Author(s):  
S. Loibl ◽  
V. Nekljudova ◽  
T. Skacel ◽  
M. Schwenkglenks ◽  
H. Lück ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Total Dose ◽  
Metastatic Breast ◽  
Dose Intensity ◽  
Phase Iii ◽  
Short And Long Term ◽  
The Impact

1065 Background: The consequences of reducing chemotherapy dose intensity might be extensive, potentially affecting short- and long-term outcomes as well as patient quality of life, the dose and schedule are of central concern in the delivery of chemotherapy. Methods: This statistical analysis was based on individual subject data of 934 patients (pts) obtained from the following prospective, open-label, randomised phase III trials in metastatic breast cancer that recruited between 1996 and 2005 investigating an anthracycline/taxane based first-line chemotherapy: CECOG trial, AGO-Mamma-1 and AGO-Mamma-3 trial. The primary objective of the analysis was to evaluate the influence of RTDI on progression free survival (PFS) in different predefined binary RTDI cuts from 75% to 95% with an interval at every 5%. Relative total dose intensity (RTDI) is the ratio of actual total dose intensity and planned total dose intensity, expressed as a percentage. RTDI quantifies dose reductions and delays, as well as premature discontinuations in treatment. Results: Overall cuts pts with higher RTDI had a shorter PFS compared to those with lower RTDI. A time dependent term for low RTDI was included in the analysis and showed the opposite effect after approximately 60 weeks. The overall median PFS was 39 weeks. Analysis of the Kaplan-Meier curve identified many early events in patients with high RTDI. We hypothesized that patients with a primary progression (PP) who have by definition a high RTDI were responsible for this effect. The PFS excluding 114 patients with PP showed no difference for patients with high compared to those with low RTDI. The median overall survival (OS) for the whole study population was 98 weeks. Excluding patients with PP, the median OS was 118 weeks (95% CI [103–136]) for those with RTDI ≥ 85% versus 96 weeks (95% CI [83–119]) if RTDI was < 85% (log-rank p = 0.0086). The results were comparable across other cut levels. Conclusions: Maintaining RTDI in patients not experiencing PP might have significant impact on overall survival. No significant financial relationships to disclose.

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 Combined chemotherapy and radiotherapy for patients with breast cancer and extensive nodal involvement.

1995 ◽  
Vol 13 (2) ◽  
pp. 435-443 ◽  
Author(s):  
O Ung ◽  
A O Langlands ◽  
B Barraclough ◽  
J Boyages
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Local Recurrence ◽  
Menopausal Status ◽  
Dose Intensity ◽  
High Dose ◽  
Combined Chemotherapy ◽  
Nodal Involvement ◽  
Standard Dosage ◽  
Distant Relapse

PURPOSE This retrospective review examines local control, freedom from distant failure, and survival for patients with nonmetastatic breast cancer with extensive nodal disease (> 10 nodes, 45 patients; or > or = 70% involved nodes, if < 10 nodes found, 19 patients). All patients received chemotherapy and radiotherapy following mastectomy. PATIENTS AND METHODS Sixty-four patients were treated between January 1980 and December 1988 at Westmead Hospital, Westmead, NSW Australia. The median follow-up duration for surviving patients was 91.5 months (range, 56 to 121). The median age was 51 years, and the median number of positive nodes was 11. Four successive protocols evolved, each with three phases, as follows: induction chemotherapy (doxorubicin or mitoxantrone, plus cyclophosphamide; three cycles), radiotherapy (50 Gy in 25 fractions to chest wall and regional nodes), then chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) of progressively shorter duration. Radiotherapy and chemotherapy were concurrent in the fourth regimen. RESULTS One patient (1.5%) developed local recurrence before distant relapse, and seven patients (11%) developed local and/or regional recurrence simultaneously or after distant relapse. The 5-year actuarial freedom from distant relapse and overall survival rates were 45% and 65%, respectively. Overall survival did not vary significantly by menopausal status, nodal subgroup, or dose-intensity. There were no treatment-related deaths. CONCLUSION Combined chemotherapy and radiotherapy in standard dosage is an acceptable approach following mastectomy for patients with extensive nodal involvement at high risk for local recurrence and distant relapse. This approach should be considered standard best therapy for any randomized trials that examine high-dose chemotherapy or bone marrow transplantation for this subgroup of patients.

scholarly journals HIGH BODY-MASS INDEX IS NOT ASSOCIATED WITH WORSE CLINICOPATHOLOGICAL CHARACTERISTICS IN PREDOMINANTLY OBESE BREAST CANCER PATIENTS

2015 ◽  
Vol 37 (4) ◽  
pp. 281-284 ◽  
Author(s):  
Y Kemal ◽  
G Demirag ◽  
F Teker ◽  
E Kut ◽  
M Kefeli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Body Mass ◽  
Menopausal Status ◽  
High Body Mass Index ◽  
Clinicopathological Characteristics ◽  
Breast Cancer Patients ◽  
High Body ◽  
Obese Population ◽  
The Impact

Background: Breast cancer (BC) is the most common cancer among women. A high body-mass index (BMI) is related to increased incidence of BC with poorer prognosis. Aim: The aim of the study was to evaluate the association in patients with BC between BMI at the time of diagnosis and biological characteristics, according to the menopausal status. Materials and Methods: This retrospective study comprised a total of 318 women with BC. Clinicopathological differences between normal, overweight and obese patients according to menopausal status were evaluated. Results: Premenopausal women had a significantly lower BMI than postmenopausal patients (28.7 vs. 31.5, respectively; p = 0.00001). No statistically significant association was determined between BMI and clinicopathological characteristics in either the premenopausal or the postmenopausal group (all p values are > 0.05). Conclusions: There are many conflicting results in literature on this relationship. The results of this study showed that a high BMI is not associated with worse clinicopathological characteristics in a predominantly obese population. In current medical oncology practice, BC should be evaluated on an individual patient basis and the impact of obesity on BC prognosis seems to be difficult to estimate especially in an obese population.

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.

A Revised Concept of the Congenital Nature of Cerebral Arteriovenous Malformations

1997 ◽  
Vol 3 (4) ◽  
pp. 275-281 ◽  
Author(s):  
P. Lasjaunias
Keyword(s):  
Negative Impact ◽  
Young Infant ◽  
Cerebral Arteriovenous Malformations ◽  
Vascular Tree ◽  
Related Factors ◽  
Entire Structure ◽  
Arteriovenous Shunts ◽  
Flow Pressure ◽  
Flow Changes ◽  
The Impact

Cerebral arteriovenous lesions are in general considered to be congenital in nature despite the fact that there is no evidence that the AV shunts diagnosed in adults are present at birth in a similar format. Construction of a vascular structure is the result of complex biological influences starting in the embryo, and continuing in the foetus, the neonate and the young infant. This vascular tree has to be maintained, repaired and modified according to metabolic demands, requiring over time the renewal of the entire structure. This is also genetically programmed and controlled. Both construction and maintenance involve repetitive steps and feedback towards the vascular tree according to the demands. Alterations in the programme or in the cellular logistics to achieve it, will create a different construction of the blood vessel wall. Analysis of the origin of the cerebrofacial endothelial cell would suggest that, the earlier a causative event occurs the larger the area of impact, and the higher the chances of apparent multifocality will be. The later the trigger occurs the more focal the defect and the smaller the lesion. If so, growth of an AVM as such should not occur; large nidi will not result from the growth of smaller ones. The impact of Rendu-Osler-Weber (ROW) disease on the venous endothelial cells and the polymorphism observed in cerebral arteriovenous shunts in ROW patients may outline the role played by the veins as the primary target in the development of cerebral AVMs. The venous and arterial angiopathy related to chronic high flow (or flow changes beyond normal equilibrium) impact a normally reacting vasculature which has been “abnormally” triggered by an AVM. This intraluminal trigger represents a “stress trigger” which can be flow, pressure or “other” related factors. This interpretation identifies the so-called AVMs to be the expression of various diseases rather than the disease itself. They are the result and negative impact of biological dysfunction of the remodelling process at the capillarovenous junction.

scholarly journals The prognostic impact of RAS on overall survival following liver resection in early versus late-onset colorectal cancer patients

2020 ◽  
Author(s):  
Alexandre A. Jácome ◽  
Timothy J. Vreeland ◽  
Benny Johnson ◽  
Yoshikuni Kawaguchi ◽  
Steven H. Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Resection ◽  
Age Of Onset ◽  
Negative Impact ◽  
Late Onset ◽  
Linear Regression Analysis ◽  
Multidisciplinary Treatment ◽  
Prognostic Impact ◽  
The Impact

Abstract Background The impact of molecular aberrations on survival after resection of colorectal liver metastases (CLM) in patients with early-age-onset (EOCRC) versus late-age-onset colorectal cancer (LOCRC) is unknown. Methods Patients who underwent liver resection for CLM with known RAS, BRAF and MSI status were retrospectively studied. The prognostic impact of RAS mutations by age was analysed with age as a categorical variable and a continuous variable. Results The study included 573 patients, 192 with EOCRC and 381 with LOCRC. The younger the age of onset of CRC, the greater the negative impact on overall survival of RAS mutations in the LOCRC, EOCRC, and ≤40 years (hazard ratio (HR), 1.64 (95% confidence interval (CI), 1.23–2.20), 2.03 (95% CI, 1.30–3.17), and 2.97 (95% CI, 1.44–6.14), respectively. Age-specific mortality risk and linear regression analysis also demonstrated that RAS mutations had a greater impact on survival in EOCRC than in LOCRC (slope: −4.07, 95% CI −8.10 to 0.04, P = 0.047, R2 = 0.08). Conclusion Among patients undergoing CLM resection, RAS mutations have a greater negative influence on survival in patients with EOCRC, more so in patients ≤40 years, than in patients with LOCRC and should be considered as a prognostic factor in multidisciplinary treatment planning.

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