Adjuvant CMF in breast cancer: comparative 5-year results of 12 versus 6 cycles.

1983 ◽  
Vol 1 (1) ◽  
pp. 2-10 ◽  
Author(s):  
G Tancini ◽  
G Bonadonna ◽  
P Valagussa ◽  
S Marchini ◽  
U Veronesi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Status ◽  
Randomized Study ◽  
Multimodal Approach ◽  
Careful Evaluation ◽  
Relapse Free Survival ◽  
Drug Induced ◽  
Free Survival ◽  
Treatment Groups ◽  
Short Period

We report the 5-yr results of a prospective randomized study comparing 12 versus 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) with the aim to evaluate the possibility of reducing the duration of adjuvant treatment without compromising the therapeutic effect of the multimodal approach. At 5-yr from mastectomy, both relapse-free survival (CMF 12: 59%; CMF 6: 65.6%) and total survival (CMF 12: 72.7%; CMF 6: 76.9%) were not significantly different in the two treatment groups. Within the two series, no difference was detected between pre- and postmenopausal patients (CMF 12: 59.3% versus 57.6%; CMF 6: 66.5% versus 63.1%), while findings were inversely related to the number of involved axillary nodes. The analysis of relapse-free survival confirmed that in both menopausal groups, relapse-free survival was not significantly affected by estrogen receptor status. Acute toxic manifestations were moderate and reversible. In particular, no drug-induced leukemia nor increased incidence of solid tumors other than breast cancer were documented in this series. Present results after 12 CMF cycles are almost identical to those of our first CMF adjuvant study. Current findings are sufficiently mature to indicate that the maximum tumor cytoreduction with CMF occurs within a relatively short period of time. To improve the results achieved with a single multidrug regimen, more intensive forms of treatment, i.e., utilizing non-cross-resistant combinations, warrant careful evaluation.

Adjuvant Chemotherapy with Fluorouracil and ccnu in Colon Cancer. Results of a Multicentric Randomized Study

1989 ◽  
Vol 75 (3) ◽  
pp. 269-276 ◽  
Author(s):  
Maurizio Marangolo ◽  
Giuseppe Pezzuoli ◽  
Ettore Marubini ◽  
Dino Amadori ◽  
Patrizia Boracchi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Randomized Study ◽  
Cure Rate ◽  
Relapse Free Survival ◽  
Multicentric Study ◽  
Free Survival ◽  
Treatment Groups ◽  
Intention To Treat ◽  
Significant Difference

To establish the effectiveness of adjuvant chemotherapy in patients with colon cancer after radical surgery, from 1980 to December 1983, 263 patients were randomized in a multicentric study to no further treatment (131 patients) or to a combination of fluorouracil (5-FU) (400 mg/m2 i.v., days 1–5) and lomustine (CCNU) (100 mg/m2 per os on day 5) every 6 weeks for 9 cycles (132 patients). The two groups were well balanced for age, sex, histology, tumor and nodal extent. Chemotherapy was not given to 30 of the 132 randomized patients, and of 98 treated patients only 38 completed the entire protocol. Analysis, as intention to treat, at 54 months did not show any significant difference between the two treatment groups in terms of relapse-free survival (surgery alone, 74.5%; surgery+adjuvant chemotherapy, 70.9%; p = 0.91). In contrast, a significant difference was observed in overall survival (surgery alone, 78.8%; surgery+adjuvant chemotherapy, 60.8%; p = 0.04). The sites of relapse were identical in the two treatment arms. In conclusion, from this study it appears that adjuvant chemotherapy with 5-FU and CCNU seems to have no efficacy in the cure rate of colon cancer patients.

scholarly journals In search of autophagy biomarkers in breast cancer: Receptor status and drug agnostic transcriptional changes during autophagy flux in cell lines

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262134
Author(s):  
Francesca Mascia ◽  
Ilya Mazo ◽  
Wei-Lun Alterovitz ◽  
Konstantinos Karagiannis ◽  
Wells W. Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Prognosis ◽  
Breast Cancer Cell Lines ◽  
Relapse Free Survival ◽  
Autophagy Flux ◽  
Drug Induced ◽  
Free Survival ◽  
Receptor Status

Autophagy drives drug resistance and drug-induced cancer cell cytotoxicity. Targeting the autophagy process could greatly improve chemotherapy outcomes. The discovery of specific inhibitors or activators has been hindered by challenges with reliably measuring autophagy levels in a clinical setting. We investigated drug-induced autophagy in breast cancer cell lines with differing ER/PR/Her2 receptor status by exposing them to known but divergent autophagy inducers each with a unique molecular target, tamoxifen, trastuzumab, bortezomib or rapamycin. Differential gene expression analysis from total RNA extracted during the earliest sign of autophagy flux showed both cell- and drug-specific changes. We analyzed the list of differentially expressed genes to find a common, cell- and drug-agnostic autophagy signature. Twelve mRNAs were significantly modulated by all the drugs and 11 were orthogonally verified with Q-RT-PCR (Klhl24, Hbp1, Crebrf, Ypel2, Fbxo32, Gdf15, Cdc25a, Ddit4, Psat1, Cd22, Ypel3). The drug agnostic mRNA signature was similarly induced by a mitochondrially targeted agent, MitoQ. In-silico analysis on the KM-plotter cancer database showed that the levels of these mRNAs are detectable in human samples and associated with breast cancer prognosis outcomes of Relapse-Free Survival in all patients (RSF), Overall Survival in all patients (OS), and Relapse-Free Survival in ER+ Patients (RSF ER+). High levels of Klhl24, Hbp1, Crebrf, Ypel2, CD22 and Ypel3 were correlated with better outcomes, whereas lower levels of Gdf15, Cdc25a, Ddit4 and Psat1 were associated with better prognosis in breast cancer patients. This gene signature uncovers candidate autophagy biomarkers that could be tested during preclinical and clinical studies to monitor the autophagy process.

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 The Alterations and Potential Roles of MCMs in Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xinyu Liu ◽  
Ying Liu ◽  
Qiangshan Wang ◽  
Siqi Song ◽  
Lingjun Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Network ◽  
Relapse Free Survival ◽  
Minichromosome Maintenance ◽  
Free Survival ◽  
Oncomine Database ◽  
Kaplan Meier ◽  
Eukaryotic Dna ◽  
Coexpressed Genes ◽  
Kaplan Meier Plotter

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.

scholarly journals Experimental, Clinical, and Morphological Analysis of H-Ras Oncoproteins for Locally Advanced Breast Cancer

2020 ◽  
Vol 8 (B) ◽  
pp. 1077-1082
Author(s):  
Ainura Maratovna Zhumakayeva ◽  
K. D. Rakhimov ◽  
I. M. Omarova ◽  
S. M. Adekenov ◽  
S. S. Zhumakayeva
Keyword(s):  
Breast Cancer ◽  
Comparative Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Positive Expression ◽  
Egfr Expression

BACKGROUND: Activated forms of RAS increase both in breast cancer and in cell lines in the presence of estimated glomerular filtration rate (EGFR) or HER2 expression. HRAS oncoproteins play an important role in enhancing the proliferation and resistance of breast cancer tumor cells to apoptosis. A number of studies have shown a significant decrease in EGFR expression after neoadjuvant chemotherapy, which has been clinical, manifested by an improvement in immediate efficacy and an increase in overall and relapse-free breast cancer survival rates. AIM: The aim of the study was to study relapse-free survival depending on the expression of the H-RAS oncoprotein in patients with breast cancer who received different treatment regimens for the farnesyltransferase inhibitor. METHODS: H-RAS status was assessed by immunohistochemistry. RESULTS: A comparative analysis of patients with negative expression of H-RAS oncoproteins showed a statistically significant increase in relapse-free survival in the subgroups who received neoadjuvant chemotherapy according to the AC regimen (adriablastin + cyclophosphamide) and AC + arglabin, compared with monotherapy by arglabin: Kruskal–Wallis= 12.56, where p = 0.001. A comparative analysis of patients with positive expression of H-RAS showed that in the subgroups treated with arglabin and AC+arglabin, there was a statistically significant increase in relapse-free survival compared with the AC subgroup: Kruskal–Wallis = 10.96, where p = 0.004. It was established that the positive expression of H-RAS negatively affects not only the direct effectiveness of neoadjuvant therapy but also worsens the rates of relapse-free survival. However, in patients with positive H-RAS expression who received arglabin in monotherapy, there was a statistically significant increase in relapse-free survival up to 16.5 ± 1.1 months compared with the standard AC regimen (13.5 ± 1.1 months) (р ˂ 0.05), the addition of arglabin to the standard AC regime also increased this indicator to 16.4 ± 1.2 months (р ˂ 0.05). CONCLUSION: These results may indicate the clinical applicability of determining H-RAS as a prognostic factor for relapse-free survival in breast cancer.

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.

BRCA-associated breast cancer in young women.

1998 ◽  
Vol 16 (5) ◽  
pp. 1642-1649 ◽  
Author(s):  
M Robson ◽  
T Gilewski ◽  
B Haas ◽  
D Levin ◽  
P Borgen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Prognostic Significance ◽  
Event Free Survival ◽  
Relapse Free Survival ◽  
Brca Mutations ◽  
Free Survival ◽  
Clinical Records ◽  
Incident Cases

PURPOSE To delineate the clinical characteristics and outcomes of breast cancer that arises in the setting of a germline BRCA mutation and to compare BRCA-associated breast cancers (BABC) with those that arise in women without mutations. PATIENTS AND METHODS We reviewed the clinical records of 91 Ashkenazi Jewish women ascertained during studies of the genetics of early-onset breast cancer. All women underwent testing for the BRCA1 mutations 185delAG and 5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2 mutation 6174delT. RESULTS Mutations were identified in 30 women (33%). BABC were less likely to present with stage I disease than cases in women without mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%), and more likely to have extensive axillary involvement (25% v 17%). These differences were not statistically significant. BABC were significantly more likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor-negative (70% v 34%, P=.04). In the entire cohort, there were no significant differences between BABC and non-BRCA-associated cancers in 5-year relapse-free survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v 68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2 years of study entry, there was a trend toward shorter event-free survival in BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA mutations were significantly more likely to develop contralateral breast cancer at 5 years (31% v 4%, P=.0007). CONCLUSION BABC present with adverse clinical and histopathologic features when compared with cases not associated with BRCA mutations. However, the prognosis of BABC appears to be similar to that of nonassociated cancer. Further studies of incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.

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