Differential expression of micro-RNAs in breast cancer with relapsed disease: A clinical data base study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12514-e12514
Author(s):  
Yadav Pandey ◽  
Zhongning Chen ◽  
Issam Makhoul

e12514 Background: Micro-RNAs (miRNAs) are small, noncoding RNA molecules that play important role in RNA silencing and post-transcriptional regulation of gene expression that are dysregulated in cancer. miRNAs are divided into oncogenic and tumor suppressor miRNAs. Both of these subtypes are known to regulate breast cancer development and progression. We studied the expression of these miRNAs before and after treatment in patients with breast cancer with relapsed disease. Methods: Data was obtained from the TCGA database. 11 patients with biopsy proven diagnosis of invasive ductal adenocarcinoma of the breast receiving adjuvant chemotherapy with relapsed disease who had tissue biopsy post-treatment were included in the study. miRNA expression was assessed in the pre- and post-treatment tissue samples. A total of 178 miRNA were analyzed after filtering out miRNA expression counts < 10. A pair-wise comparison of the differential expression of miRNA before and after treatment with adjuvant chemotherapy was analyzed using a quasi-likelihood F test implemented by bioconductor package, edgeR. This package is well documented for analyzing RNA-seq data due to adjustment for biological variations and measuring error using a negative binomial distribution. The expression of miRNA |Log2FC| > 1 and P value < 0.05 were obtained. Results: Out of 11 female patients, 10 were Caucasian. 9 out of 11 patients’ tumors were Estrogen Receptor positive; 8 patients had progesterone Receptor positive and 1 patient had Human epidermal growth factor receptor2 positive cancer. Of the 178 miRNAs of interest, we found 14 miRNA that are differentially expressed. The miRNA that are up-regulated post-treatment were hsa-miR-148a, hsa-miR-126, hsa-miR-142, hsa-miR-210, hsa-miR-374a, hsa-miR-192. The miRNA that were down-regulated were hsa-miR-197, hsa-miR-155, hsa-miR-149, hsa-miR-365a, hsa-miR-365b, hsa-miR-484, hsa-miR-339 and hsa-miR-3653. Among the miRNA up-regulated post-treatment, miR-148 and miR-126 are known major tumor suppresser miRNA whereas miR-210 and miR-374a are major oncogenic miRNA in breast cancer. Among the miRNA down-regulated post treatment, miR-155 is major oncogenic miRNA whereas miR-365 is major tumor suppressor miRNA in breast cancer. Conclusions: There is mixed expression profile of tumor suppressor miRNA and oncogenic miRNA molecules between before and after treatment in patients with breast cancer with relapsed disease. Further studying these miRNA molecules can help us better understand about the tumor progression and disease relapse.

2021 ◽  
Vol 20 ◽  
pp. 153473542098834
Author(s):  
Abdolazim Sedighi Pashaki ◽  
Kamal Mohammadian ◽  
Saeid Afshar ◽  
Mohammad Hadi Gholami ◽  
Abbas Moradi ◽  
...  

Objective: Fatigue associated with malignant conditions and their treatments is a disabling condition. This trial assessed the anti-fatigue effects of melatonin coadministration during adjuvant treatment of patients with the breast cancer. Material and Methods: Patients with breast cancer were randomly assigned to receive melatonin or placebo during adjuvant chemotherapy and radiotherapy. Thirty-seven patients were randomly enrolled in each group. The mean ages of patients in the intervention and control groups were 50.47 ± 10.79 and 46.05 ± 10.55 years, respectively ( P = .223). The intervention group received oral melatonin (18 mg/day) from 1 week before until 1 month after the adjuvant radiotherapy. The level of fatigue was assessed before and after intervention using Brief Fatigue Inventory (BFI) in both groups. To analyze data, the Student’s t-test and the Chi-square test were used at a significance level of P ≤ .05. Results: The BFI score was similar before the intervention in both groups, however, after the intervention, it was significantly lower in the melatonin group ( P < .001). Moreover, the frequency of severe fatigue in the melatonin group was significantly lower than in the placebo group after intervention (42.1% vs 83.3%, P < .001). Conclusion: Coadministration of melatonin during adjuvant chemotherapy and radiotherapy of women with breast cancer decreased the levels of fatigue associated with the malignant condition and its treatments.


2020 ◽  
Author(s):  
Gerardo I. Magallanes-Garza ◽  
Sandra K. Santuario-Facio ◽  
Arlina F. Varela-Varela ◽  
Servando Cardona-Huerta ◽  
Pablo Ruiz-Flores ◽  
...  

Abstract Background: Studies of molecular changes occurring before and after neo-adjuvant chemotherapy (NCT) for breast cancer may unveil genetic biomarkers to predict therapy response. This study aimed at identifying genomic changes in breast primary tumors of patients under NCT. Gene expression changes were correlated with pathological response and survival.Methods: Gene expression profiles in tissue samples from pre and post NCT were obtained by a non-supervised classification analysis. Thirty-nine patients were classified according to their response to the chemotherapy as pathologic complete responders or non-responders (pCR and no-pCR, respectively). Overall survival was assessed by comparing gene expression values before NCT using the Log-rank (Mantel-Cox) test. Results: A signature constituted by 43 genes was obtained to stratify pCR and no-pCR patients after NCT (FC = + 3, FDR p -value < 0.0298). These genes were involved in regulation of the mitotic nuclear division and the anaphase-promoting complex-dependent catabolic process. Remarkably, over-expression of NUSAP1 and KIAA0101 were associated to poor overall survival. Conclusions: A new expression signature evaluating response for the neo-adjuvant chemotherapy stratified pathological response. The expression levels of NUSAP1 and KIAA0101 before and after the neo-adjuvant therapy may be useful to predict overall survival.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1010-1010
Author(s):  
B. Arun ◽  
V. Valero ◽  
G. Yin ◽  
G. Babiera ◽  
J. L. Murray ◽  
...  

1010 Background: Short-term chemoprevention trials offer a convenient model to screen chemopreventive agents and identify endpoint biomarkers. One of the potential agents is celecoxib (C), which has antiproliferative and apoptosis inducing properties. In this prospective study, our primary aim was to evaluate changes in proliferation induced by C in breast tissue of high risk women. Here, we report changes in estrogen receptor (ER) proliferation index. Methods: 42 eligible high risk women were enrolled into the study, underwent fine needle aspiration (FNA) and started celecoxib treatment at 400 mg BID. Median age: 51.9 years. Risk factors: Gail risk > 1.67% (n=13), lobular carcinoma insitu (n=13), atypical hyperplasia (n=11), previous history of breast cancer (n=5). For ER and Ki-67 testing, thin preparations slides were incubated with primary mouse monoclonal antibody 6F11 against the ER and clone MIB-1, respectively. Appropriate negative and positive controls were included. At least 100 epithelial cells were evaluated per slide. Immunoreactivity for each marker was scored as the percentage of positive nuclei. We assessed the difference in ER and Ki-67 levels before and after treatment using a Wilcoxon signed rank test. Results: The average pre-treatment ER expression in FNA samples was 35.9% and Ki-67 was 2.4%. 19 (45%) showed hyperplasia or atypical hyperplasia. 39 patients underwent also post-treatment FNAs. The pre-and post treatment ER expression in this group was 35.7% (range 0–100%) and 27.4% (range: 0–100%), respectively. The difference in ER levels was statistically significant (p = 0.04). Twenty-six patients had Ki-67 levels measured both before and after treatment. The median difference in Ki-67 levels was 0 (range 0- 5). This change was not statistically significant (p = 0.63). Conclusions: We have completed accrual to a prospective short-term chemoprevention trial with celecoxib. We have found a significant downregulation of ER expression with 6 months celecoxib. Since ER expression is a marker of proliferation, this finding confirms celecoxibs antiproliferative properties. Currently, we have not observed a change in Ki-67; this could be partly due to the small number of samples and the fact that Ki-67 is low in normal epithelium. [Table: see text]


2021 ◽  
Author(s):  
Jenny Eva Maria Heiman ◽  
Aron Onerup ◽  
David Bock ◽  
Eva Haglind ◽  
Roger Olofsson Bagge

Abstract PurposeWe conducted a randomised controlled trial (PhysSURG-B) to assess the short- and long-term effects of a non-supervised physical activity intervention at the time of breast cancer surgery. Here we report a secondary outcome, quality of life (QoL).MethodsFemale patients planned for surgery were randomly assigned to either an intervention of 30 minutes of self-administered physical aerobic activity daily 2 weeks before and 4 weeks after surgery, or control. QoL was assessed with questionnaires at baseline, 4 weeks and 12 months postop using the instruments FACT-B, RAND-36 and EQ-VAS.ResultsOut of 354 included participants at 12 months follow-up after surgery, 287 were available for QoL analysis. Comparing intervention to control, the results for the FACT- B score at 4 weeks showed an odds ratio (OR) of 0.975 (95% CI 0.636-1.495) and at 12 months an OR of 0.883 (95% CI 0.581-1.342). The subgroup of patients receiving adjuvant chemotherapy had significantly lower FACT-B at 12 months compared to no chemotherapy (OR 0.475, 95% CI 0.300-0.735). EQ-VAS showed OR 1.163 (95% CI 0.760-1.779) and 0.817 (95% CI 0.536-1.244) at 4 weeks and 12 months, respectively. RAND-36 domains “role limitations due to physical health” and “pain” showed a decrease at 4 weeks in both groups, returning towards baseline at 12 months follow-up.ConclusionAn intervention of non-supervised physical activity before and after surgery for breast cancer had no effect on QoL. Patients receiving adjuvant chemotherapy had significantly lower QoL, regardless of study group.Trial registrationClinicalTrials.gov registration number: NCT 02560662. Registered 25 September, 2015.


2021 ◽  
Vol 9 (B) ◽  
pp. 1570-1574
Author(s):  
Imam Hafidh Zaini ◽  
Widyanti Soewoto ◽  
Ida Bagus Budhi

AIM: This study aims to evaluate the effect of adjuvant chemotherapy on estradiol levels in patients with HER 2-overexpression breast cancer in a developing country. METHODS: This comparative study with pre- and post-design model observation approach, involving patients with HER 2-overexpression breast cancer who had undergone surgery and had never received chemotherapy or hormonal therapy before, who were then given adjuvant chemotherapy. Estradiol levels were measured before and after chemotherapy. The study was carried out in the surgical oncology division of RSUD Dr. Moewardi (RSDM) Surakarta from January 2020-December 2020. Descriptive data are presented in a frequency table based on age, menstrual status, parity status, breastfeeding status, contraception, contraception duration, family history, stage, and histological grade. Before and after chemotherapy in patients with breast cancer, the estradiol levels employed the paired sample t-test of the Wilcoxon rank test because the data did not meet the normality assumption. RESULTS: From the total data of 21 patients, 15 patients experienced a decrease in estradiol levels after chemotherapy, while six patients underwent an increase. The mean estradiol level before chemotherapy was 89.41 pg/ml, whereas the mean estradiol level after chemotherapy was 55.90 pg/ml. It indicates a difference in the decrease in estradiol levels of 33.51 pg/ml. The statistical test results also obtained a p-value of = 0.033 (p < 0.05), which signifies a significant difference between estradiol levels before and after chemotherapy. Thus, chemotherapy is effective in lowering estradiol levels in patients with breast cancer. CONCLUSION: Chemotherapy affects decreasing estradiol levels in patients with HER2 overexpression breast cancer.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11626-e11626
Author(s):  
I. I. Schnirer

e11626 Background: In Israel, the majority of patients receiving doxorubicin (A) are treated with dexrazoxan (D). A retro-active study was carried out on cardiac effects of A and D on female patients receiving adjuvant chemotherapy for Stage 2 breast cancer. Methods: 34 newly-diagnosed chemotherapy-naïve female patients with Stage 2 breast cancer, received anthracycline-based chemotherapy treatment A with D ± Herceptin (HER). Cardiotoxicity was assessed by echo-cardiograph pre- and post- treatment, and thereafter every 3 months for a period of 2 years, and was defined by presence of CHF or a reduction in resting LVEF to <45% or to ≥15% below baseline echo-cardiograph. Results: 34 patients were eligible for assessment. The mean age was 52, ranging from 24 to 78. Chemotherapy regimen consisted of 4 cycles of A + cyclophosphamide + D ± HER (HER treatment over a period of one year) + paclitaxel (PAC) (12 courses). Of the 34 patients, 7 (20.5%) were Her2 new positive. 17 patients (50%) were estrogen (ER)/progesterone (PR) positive. 9 patients (26.4%) were triple negative. 2 of the Her2 new positive patients were also ER/PR positive. Average m2 per study population was 1.63 (mean range being 1.39 - 1.87). Average A dosage was 60mg/m2 and mean D dose was 391.2mg (between 333.6mg and 448.8mg). Ratio of A to D was 1:10. Echo-cardiograph pre- treatment ranged from 80% - 60%, a normal range according to the New York Health Association (NYHA). Post-treatment echo-cardiograph ranged from 70% - 45%. One patient from HER positive group (generally experiencing increased cardiotoxicity by 4%) showed decrease in LVEF by 14.3% (14.2% of Her2 new patients). Remaining patients showed no change. One patient from ER/PR positive group experienced a 12.3% reduction in LVEF, representing 5.88% of the ER/PR patients. Remaining ER/PR positive patients remained unchanged, with one patient showing increased LVEF from 60% to 70%. The triple negative patient showed no change in their echo- cardiograph results. Conclusions: This study confirms that no scientific or clinical-based evidence was found of anthracycline- based cardiotoxicity following administration of A plus D, in accordance with published medical evidence. D should be a standard of care for anthracycline-based chemotherapy. No significant financial relationships to disclose.


2018 ◽  
Vol 2 (1) ◽  
pp. 01-05
Author(s):  
Srileela Movva ◽  
Srinivasa Rao Konijeti

Background: Women with breast cancer are at increased risk for the development of osteoporosis and skeletal fractures, as consequences of aromatase inhibition or chemotherapy-induced ovarian failure. We investigated the effect of adjuvant chemotherapy on biochemical markers of bone formation and resorption as well as on bone mineral density (BMD) of non-metastatic breast cancer (NMBC) postmenopausal Egyptian women. Methods: We followed 100 newly diagnosed women with T1-3 N0-2 M0 breast cancer, who had a mean age (±SD) of 55.06±8.78 year, before and after receiving 6-cycles of CAF chemotherapy treatment protocol. All participant women were subjected to blood biochemical analysis for determining serum levels of: erythrocyte sedimentation rate, calcium, alkaline phosphatase (ALP), bone specific alkaline phosphatase (S.ALP), Osteocalcin, carboxytelopeptide of collagen type I (CTx-I), 25-Hydroxyvitamin D, Parathyroid Hormone (PTH) and tumor marker CA15-3. Segmental and total BMD were also investigated using Dual X-ray Absorptiometry technique. Results: We found ALP, S.ALP, and CTx-I levels were significantly lower (p<0.001), while PTH levels to be significantly higher for all women after chemotherapy as compared to their initial state before chemotherapy. Both segmental and total BMD, and consequently T- and Z-Scores after chemotherapy were significantly (p<0.01) lower than their levels before chemotherapy. We developed prediction mathematical formulae for spine, pelvis and total BMD for all women before and after chemotherapy. Conclusions: Adjuvant chemotherapy is responsible for decreasing both biochemical markers of bone formation and resorption as well as for decreasing segmental and total BMD in NMBC postmenopausal Egyptian women. We believe the mathematical formulae developed on basis of the two individual variables Age and BMI can be useful for assisting the clinician to frequently monitor bone health status of breast cancer patients in similar conditions.


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