Purpose: To study the patient load, treatment pattern, survival outcome and its predictors in patients with brain metastases treated by radiotherapy. Materials and Methods: Data for patients with brain metastases treated by radiotherapy between 2003 and 2007 were collected from medical records, the hospital information system database, and a population-based tumor registry database until death or at least 5 years after treatment and retrospectively reviewed. Results: The number of treatments for brain metastases gradually increased from 48 in 2003 to 107 in 2007, with more than 70% from lung and breast cancers. The majority were treated with whole brain radiation of 30 Gy (3 Gy X 10 fractions) by cobalt-60 machine, using radiation alone. The overall median survival of the 418 patients was 3.9 months. Cohort analysis of relative survival after radiotherapy was as follows: 52% at 3 months, 18% at 1 year and 3% at 5 years in males; and 66% at 3 months, 26% at 1 year and 7% at 5 years in females. Multivariate analysis demonstrated that the patients treated with combined modalities had a better prognosis. Poor prognostic factors included primary cancer from the lung or gastrointestinal tract, emergency or urgent consultation, poor performance status (ECOG 3-4), and a hemoglobin level before treatment of less than 10 g/dl. Conclusions: This study identified an increasing trend of patient load with brain metastases. Possible over-treatment and under-treatment were demonstrated with a wide range of survival results. Practical prognostic scoring systems to assist in decision-making for optimal treatment of different patient groups is absolutely necessary; it is a key strategy for balancing good quality of care and patient load.
However, long-term results of retrospective studies suggest that, for the great majority of individuals, mastectomy or conservative surgery with radiation therapy were be equally effective. The results at 5 and 10 years from prospective randomized trials indicate that survival following primary radiation therapy for early breast cancer is equivalent to that fellowing mastectomy. When competently Performed, Primary radiation therapy gives highly satisfactory cosmetic results and acceptably low rates of local tumor recurrence. A number of controversial issues remain concerning patient evaluation and selection and the optimal techniques of treatment, both surgical and radiotherapeutic. In addition, further work is needed to clearity the best way to integrate primary radiotherapy with adjuvant systemic treatment. And further follow-up of these patients with primary radiation therapy for early beast cancer will be required for ultimate proof of the relative merits. A case which was conservative surgery and radical irradiation of early breast cancer with review of literatures will be done.
Purpose: To research the association between pre-treatment elevated platelet count and clinicopathologic characteristics in breast cancer (BC), as well as explore the relationship between pre-treatment elevated platelet count and HER2 status and prognosis of BC patients. Materials and Methods: A retrospective cohort of BC patients who were newly diagnosed or treated by surgery only and had pathological detection results and platelet values in the Department of Oncology, the First Affiliated Hospital of Liaoning Medical College were enrolled from 1/1/2008 until 31/12/2009, and followed up until 31/12/2014. Age, thrombocyte parameters before chemotherapy and/or radiotherapy, immunohistochemical (IHM) indexes, and regional lymph node (LN) involvement and progression-free survival (PFS) were recorded. Results: A total of 447 eligible subjects were included in this research. As we analyzed, for HER2, positive and negative, the incidence rates of elevated platelet count were 25.8% and 14.7% (P<0.05). In the Cox proportional hazards model both variables were independent risk factors for BC (for HER2, OR, 0.592, 95% confidence interval, CI, 0.355 to 0.985, P=0.044;f or PLT, OR, 0.998, 95% CI, 0.996 to 1.000, P=0.042). For ER, PR, Ki67 and LN involvement, the differences were not statistically significant (P>0.05). Conclusions: In this research, pre-treatment elevated level of platelet count demostrated a significantrelationship with HER2 amplification/overexpression, and both variables significantly influenced the prognosis of BC. However, elevated platelet count did not exhibit any association with ER, PR, Ki67 and LN involvement.
Small molecule tyrosine kinase inhibitors targeting HER 2 receptors have emerged as an important therapeutic approach in inhibition of downstream proliferation and survival signals for the treatment of breast cancers. Recent drug discovery efforts have demonstrated that naturally occurring polyphenolic compounds like delphinidin have potential to inhibit proliferation and promote apoptosis of breast cancer cells by targeting HER2 receptors. While delphinidin may thus reduce tumour size, it is associated with serious side effects like dysphonia. Owing to the narrow therapeutic window of delphinidin, the present study aimed to identify high affinity compounds targeting HER2 with safer pharmacological profiles than delphinidin through virtual screening approaches. Delphinidin served as the query parent for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. The compounds retrieved were further subjected to Lipinski and Verber's filters to obtain drug like agents, then further filtered by diversity based screens with a cut off of 0.6. The compound with Pubchem ID: 91596862 was identified to have higher affinity than its parent. In addition it also proved to be non-toxic with a better ADMET profile and higher kinase activity. The compound identified in the study can be put to further in vitro drug testing to complement the present study.
EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx-Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2- BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC.
Background Postmastectomy adjuvant therapy is used to prevent locoregional recurrence and improve overall breast cancer specific survival rates. However, it can adversely affect the cosmetic results of reconstruction. Therefore, the authors examined flap stability and patients' satisfaction with immediate breast reconstruction after adjuvant therapy. Methods We retrospectively reviewed the medical records of 204 patients from January 2006 to November 2011. For complication rates, the authors categorized the patients who underwent the immediate breast reconstruction into 4 groups: adjuvant chemotherapy and radiotherapy group, adjuvant chemotherapy only group, adjuvant radiotherapy only group, and the group that did not undergo adjuvant therapy. For comparison of patients' satisfaction, the study was performed with an additional 16 patients who had undergone delayed breast reconstruction. Results Regarding complication rates, the group that had undergone adjuvant therapy showed no significant difference compared to the group that did not undergo adjuvant therapy. In evaluating the patients' satisfaction, there was no significant difference. Conclusions Even after adjuvant therapy, immediate breast reconstruction showed good results with respect to flap stability and patients' satisfaction. Immediate breast reconstruction and adjuvant therapy is a safe and useful option for breast cancer patients.
Deng, Qian-Qian;Huang, Xin-En;Ye, Li-Hong;Lu, Yan-Yan;Liang, Yong;Xiang, Jin
Asian Pacific Journal of Cancer Prevention
/
v.14
no.1
/
pp.413-417
/
2013
Purpose: This phase II study was undertaken to determine the efficacy and safety of Loubo$^{(R)}$ (Lobaplatin) in combination with pemetrexed in treating patients with metastatic breast cancer who failed to respond to anthracycline or taxanes. Patients and Methods: Metastatic breast cancer cases who had previously received an anthracycline and a taxane in either adjuvant or metastatic settings, were enrolled. All patients were recruited from Jiangsu Cancer Hospital and Research Institute, and were treated with Loubo$^{(R)}$ (Lobaplatin) 35 $mg/m^2$ (intravenous; on day 1) and pemetrexed 500 $mg/m^2$ (intravenous; on day 1) every 21 days. Efficacy and side effects were evaluated after at least two cycles of chemotherapy. Results: All eligible 19 patients completed at least 2 cycles of chemotherapy with pemetrexed and lobaplatin, and were evaluable. Overall, 3 (15.8%) patients achieved partial response, 11 (57.9%) stable disease, 5 (26.3%) progression of disease, with no complete remission. Response rate was 15.8%, disease control rate was 42.1%. The median survival time was 10.3 months. Neutrophil suppression occurred in 36.8% of patients who had grade 2 toxicity, and 26.3% had grade 3, 26.4% had grade 4. Thrombocytopenia was encountered as follows: 21.1% grade 2, 15.8% grade 3 and 5.5% grade 4. Incidences of anemia were 10.5% in grade 2, 5.3% grade 3 and 0% grade 4. Only 5.3% of patients required packed red blood cell transfusion. Grade 3 digestive tract toxicity occurred in 5.5% of patients. Other toxicities included elevated transaminase,oral mucositis and skin rashes. Conclusions: The regimen of lobaplatin and pemetrexed is modestly active in metastatic breast cancer patients who failed anthracycline or taxanes, and the toxicity profile suggesting that the doses of chemotherapy should be further modified.
Kim, Jung Nam;Chae, Han;Kwon, Young Kyu;Kim, Byung Joo
Journal of Physiology & Pathology in Korean Medicine
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v.28
no.2
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pp.162-168
/
2014
Fruits of Schisandra chinensis (SC) Baill are considered a traditional herbal medicine for the treatment and alleviation of various diseases. The purpose of this study was to investigate the anti-cancer effects of SC extract in human breast adenocarcinoma cells (MCF-7). We used human breast adenocarcinoma cell line, MCF-7 cells. We examined cell death by MTT assay and caspase 3 and 9 assay with SC extract. To examine the inhibitory effects of SC extract, cell cycle (sub G1) analysis and mitochondrial membrane depolarization was done the MCF-7 cells after one day with SC extract. In addition, to investigate the transient receptor potential melastatin 7 (TRPM7) currents, we used the whole cell patch clamp techniques. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in MCF-7 cell growth and survival. SC extract inhibited the growth of MCF-7 cells in a dose-dependent fashion. Also we showed that SC extract induced apoptosis in MCF-7 cells by MTT assay, caspase 3 and 9 assay, sub-G1 analysis and mitochondrial membrane depolarization. SC extract inhibited the TRPM7 currents in MCF-7 cells and in TRPM7 overexpressed HEK 293 cells. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SC extract-induced cell death. Our findings provide insight into unraveling the effects of SC extract in human breast adenocarcinoma cells and developing therapeutic agents against breast cancer.
Purpose: The purposes of this study is to provide basic informations on oriental medical research and treatment through analysis of breast cancer patients, who visited M $\mu$ integrative cancer center, O O university East-West neo medical center. Methods: Electronic medical records of 106 breast cancer patients who visited oriental medical center from June 2, 2006 to February 28, 2008 were selected to collect clinical data of those patients. Clinical data were analyzed for types of clinical characteristics, and received therapies. For analysis of survival and recurrence, Kaplan-Meier method was used. All the data were processed and analyzed using SPSS version 13.0. Results: Average age of breast cancer patients, who visited oriental medical center was 48.72 ($\pm$10.13). The stage distribution record indicated stage I (5.8%), stage II (7.0%), stage III (5.8%), and stage IV (81.4%). Original purposes of patients were analyzed to be supplementary treatment for western therapy (68.9%), treatment for recurrence prevention (18.9%), and oriental medical treatment (12.2%) in order. While receiving oriental medical treatment, 60.4% of patients received conventional medical treatment simultaneously. Conclusion: Majority of patients who visited oriental medical hospital were stage IV at terminal stage and mainly visited for the purpose of supportive care. Further clinical study of breast cancer patients is needed to validate the effectiveness of oriental medical treatment based on this study.
Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.
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