Does Adjunctive Naturopathic Care Decrease Survival Rates in Breast Cancer Patients?

FAM64A is a mitotic regulator which promotes cell metaphase-anaphase transition and is highly expressed in a cell-cycle-dependent manner. In this study, we examined the clinicopathological and prognostic significance of FAM64A mRNA expression in gynecological cancers. We conducted a bioinformatics analysis of FAM64A mRNA expression using Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), xiantao, The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), and Kaplan-Meier (KM) plotter databases. FAM64A expression was elevated in breast, cervical, endometrial, and ovarian cancers when compared with normal tissue. Expression was positively correlated with white race, low T stages, infiltrating ductal carcinoma, or favourable PAM50 classification in breast cancer patients, and with clinical stage, histological grade and TP53 mutation, and endometrial cancer serous subtype. FAM64A expression was negatively associated with overall and/or recurrence-free survival rates in breast and endometrial cancer patients, while the opposite was observed in cervical and ovarian cancer patients. FAM64A functioned as an independent predictor of overall and disease-specific survival in breast cancer patients. FAM64A-correlated genes were involved in ligand-receptor interactions, and chromosomal, cell cycle, and DNA replication processes in breast, cervical, endometrial and ovarian cancers. Top hub genes primarily included cell cycle-related proteins in breast cancer, mucins and acetylgalactosaminyl transferases in cervical cancer, kinesin family members in endometrial cancer, and synovial sarcoma X and the cancer/testis antigen in ovarian cancer. FAM64A mRNA expression was positively related to Th2 cell infiltration, but negatively associated with neutrophil and Th17 cell infiltration in breast, cervical, endometrial, and ovarian cancers. FAM64A expression may be considered a potential biomarker reflecting carcinogenesis, histogenesis, aggressive behaviour, and prognosis in gynecological cancers. Impact statement What is already known on this subject? FAM64A is located in cell nucleolar and nucleoplasmic regions, and during mitosis it putatively controls metaphase-to-anaphase transition. FAM64A appears to regulate different physiological processes, including apoptosis, tumorigenesis, neural differentiation, stress responses, and the cell cycle. What the results of this study add? FAM64A expression was up-regulated in breast, cervical, endometrial, and ovarian cancers, and positively correlated with white race, low T stages, infiltrating ductal carcinoma, or favourable PAM50 classification in breast cancer patients, and with clinical stage, histological grade, and TP53 mutation, and a serous subtype in endometrial cancer. FAM64A expression was negatively associated with overall and/or recurrence-free survival rates in breast and endometrial cancer patients, while the opposite was observed in cervical and ovarian cancer patients. FAM64A functioned as an independent predictor of overall and disease-specific survival in breast cancer. FAM64A-correlated genes were involved in ligand-receptor interactions, chromosomal, cell cycle, and DNA replication processes, while FAM64A mRNA expression was positively related to Th2 cell infiltration but negatively correlated with neutrophil and Th17 cell infiltration in four gynecological cancers. What the implications of these findings for clinical practice and/or further research? In the future, abnormal FAM64A mRNA expression may serve as a biomarker of carcinogenesis, histogenesis, aggressiveness, and prognosis in gynecological malignancies.

Background: Recent reports show that the preoperative systemic inflammatory response status correlate with the survival rate in cancer patients. The Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT), Neutrophil Lymphocyte Ratio (NLR) and Platelet Lymphocyte Ratio (PLR) score are used as screening tools for immunonutritional status and reported to be a predictor of postoperative recurrence in patients with various gastrointestinal cancers. However, the clinical importance of these scoring in breast cancer has not been fully elucidated. The aim of this study is to investigate the clinical impact of preoperative systemic inflammatory response on long-term survival of breast cancer patients. Patients and Methods: We retrospectively analyzed 653 consecutive stage I-III breast cancer patients who were treated from January 2002 to December 2013. The PNI score was calculated as 10 x serum albumin (g/dl) + 0.005 x total lymphocyte count (per mm3). The CONUT score is calculated from three parameters, serum albumin, cholesterol, and total lymphocytes count. The patients were divided into two groups according to each value. The uni- and multivariate Cox regression analyses were performed to evaluate the prognositic value of the systemic inflammatory response in breast cancer. Results: The malnutritional or high SIR status was observed in 170 (26%),131 (20%), 119 (18%) and 226 (35%) patients as low-PNI, high-CONUT, elevated NLR and PLR, respectively. The relapse-free survival (RFS) and overall survival (OS) rates were significantly lower in the low-PNI group (RFS: p<0.0001, OS: p<0.0001) and high-CONUT group (RFS: p=0.0009, OS: p=0.0018). No significant association was found between NLR, PLR and prognosis. In the multivariate analysis, low-PNI was the independent prognostic factors for OS (HR4.71, p=0.0023). In the subset analysis, the low-PNI group showed poor prognosis especially in the postmenopausal, hormone receptor negative patients. The low-PNI also had poorer prognosis in post-recurrence survival. Conclusions: The preoperative systemic inflammatory response, especially PNI, is a strong independent predictor of long-term survival among breast cancer patients. Citation Format: Nami Yamashita, Sayuri Akiyoshi, Eiki Sano, Tomoko Shigechi, Yuichi Hisamatsu, Eriko Tokunaga, Eiji Oki, Masaki Mori. The preoperative systemic inflammatory response as a strong prognostic factor in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-07-09.

PurposeMultiple primary malignancies (MPMs) caused by breast cancer treatment are well described, but only few studies to date describe which other previous primary malignancies (OPPMs) occur before breast cancer. The purpose of the present study was to evaluate the prevalence of OPPMs in patients with breast cancer between 2007 and 2018 in Western Sweden.MethodsPatient selection was performed using both pathology reports at Sahlgrenska University Hospital (Sweden) and the Swedish Cancer Registry. All newly diagnosed breast cancer patients were screened for presence of OPPM.ResultsIn total, 8031 breast cancer patients were diagnosed at Sahlgrenska University Hospital between 2007 and 2018. The prevalence of breast cancer patients with OPPMs (n = 414) increased from on average 2.6% to 8.2% during this 12-year period and ranged from 17 to 59 patients annually. The most striking increase in prevalence was found among the gynecological tumors (endometrium and ovarian adenocarcinomas), malignant melanomas and gastrointestinal malignancies. These findings were validated using data of the Swedish Cancer Registry.ConclusionsThe overall survival rates for cancer patients have improved tremendously during the past 40 years, in part due to individually tailored therapies and screening programs. Our study revealed an increasing trend of OPPMs in breast cancer patients.

BackgroundBreast cancer is the second leading cause of cancer related deaths in women worldwide. Reports about the early diagnosis of breast cancer are suggestive of an improved clinical outcome and overall survival rate in cancer patients. Therefore, cancer screening biomarker for early detection and diagnosis is urgently required for timely treatment and better cancer management. In this context, we investigated an association of cancer testis antigen, A-Kinase anchor protein 4 (AKAP4) with breast carcinoma.Methodology/FindingsWe first compared the AKAP4 gene and protein expression in four breast cancer cells (MCF7, MDA-MB-231, SK-BR3 and BT474) and normal human mammary epithelial cells. In addition, 91 clinical specimens of breast cancer patients of various histotypes including ductal carcinoma in situ, infiltrating ductal carcinoma and infiltrating lobular carcinoma and 83 available matched adjacent non-cancerous tissues were examined for AKAP4 gene and protein expression by employing in situ RNA hybridization and immunohistochemistry respectively. Humoral response against AKAP4 was also investigated in breast cancer patients employing ELISA. Our in vitro studies in all breast cancer cells revealed AKAP4 gene and protein expression whereas, normal human mammary epithelial cells failed to show any expression. Using in situ RNA hybridization and immunohistochemistry, 85% (77/91) tissue specimens irrespective of histotypes, stages and grades of breast cancer clinical specimens revealed AKAP4 gene and protein expression. However, matched adjacent non-cancerous tissues failed to display any AKAP4 gene and protein expression. Furthermore, humoral response was observed in 79% (72/91) of total breast cancer patients. Interestingly, we observed that 94% (72/77) of breast cancer patients found positive for AKAP4 protein expression generated humoral response against AKAP4 protein.ConclusionsCollectively, our data suggests that AKAP4 may be used as serum based diagnostic test for an early detection and diagnosis of breast cancer and may be a potential target for immunotherapeutic use.

Cervical cancer has a high incidence with a low survival rate. The clinicopathological profile and risk factors cause this. Most cervical cancer sufferers are late in realizing this, contributing to the severity suffered. Radiation has a very important role because it is a therapy that can be done in cervical cancer patients who have experienced an advanced level of severity. This study aims to determine the survival and influence of the clinicopathological and risk factors of radiation patients as a consideration in selecting effective therapy to increase the survival rate of cervical cancer patients. The benefit of this research is to help evaluate cervical cancer management procedures with radiation therapy applied in many hospitals in Indonesia to increase the success of therapy for cervical cancer. An analytical observational study with a retrospective cohort type using medical record data with samples of all patients diagnosed with cervical cancer who received radiation therapy from January to December 2017. Samples in this study were 111 patients. This study revealed that the five-year survival rate of cervical cancer patients was only 53.1%. There was an influence on the clinicopathological stage (p<0.000), histopathology (p<0.000), lymph node status (p<0.000), degree of differentiation (p<0.001), and risk factors for age (p<0.038), parity (p<0.001), education (0.022), marital status (0.001), contraceptive use (p<0.000), and BMI (p<0.000) which resulted in a log-rank p-value <0.05, so it was concluded that there was an effect between these variables on cervical carcinoma survival rate. Multivariate, it was found that radiation, histopathology, lymph node status, contraception, and BMI had a significant effect (p<0.005) on the survival rate of cervical cancer patients. The results of this study indicate that the survival rate of cervical cancer patients is still low, and there is a clinicopathological and risk factors that influence the survival rate of cervical cancer patients.

Introduction. The complex of transcriptional proteins of NF-kB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) family deservedly attracts attention as a factor capable of determining the course of malignant disease. Its promising study in combination with the expression of proinflammatory gene IL6 in patients with parotid cancer (PSG) is associated with the development of modulation of malignant disease treatment and risk assessment of the disease course. Aims — to determine the effect of the expression activity of the proinflammatory interleukin-6 gene and the NFKB1 transcriptional gene on the survival rate of patients with parotid cancer. Materials and methods. A cohort retrospective study was conducted in two groups. The epidemiological group of patients included 140 people from the cancer registry of Rostov region. The clinical part of the work was carried out on 25 patients with PSG cancer of both sexes aged 50 to 80 years. Followup period of the patients after radical surgery was 18 years. Expression activity of NFKB1 and IL6 genes was estimated by real-time PCR in tumor and conditionally healthy tissue. Patient survival rate was analyzed using Kaplan-Meier method. Results. According to the results of the survival analysis in the epidemiological group, the probability that an PSG cancer patient would survive the first year after diagnosis was 95.7%, three years — 82.4%, five years — 70.9% and 10 years — 31.2%. A comparative study of gene expression levels in tumor tissue samples compared to conditionally healthy tissue revealed an increase (p<0.001) in the relative index for both the IL6 gene (5.7 times) and the NFKB1 gene (7.9 times).><0.001) in the relative index for both the IL6 gene (5.7 times) and the NFKB1 gene (7.9 times). Discussion. Analysis of our data showed the possibility of using the complex evaluation of NFKB1 and IL6 gene expression in the cells of tumor samples of PSG cancer tissue obtained during surgery to predict the long-term survival of patients after surgical treatment. Conclusions. The expression profile of NFKB1 gene in tumor tissue was a proven prognostic factor determining the course of the disease in patients with PSG cancer, which should be taken into account when forming the prognosis of the disease. The expression of IL6 gene expression in tumor cells had no independent effect on the survival rate of PSG cancer patients, but contributed to the functional activation of NFKB1 transcription gene.

In this study, we investigate the main factors that affect survival rates of colorectal cancer (CRC) patients in the state of Texas with respect to race group. CRC is the second leading cause of mortality in the USA as per recent ACS data. The five-year survival rate of patients diagnosed with localized-stage disease is 90%, survival declines to 71% and 14% for patients diagnosed with regional and distant stages, respectively. Some of the factors associated with this disease that we examined in this study include insurance, treatment, poverty, gender, age, stage, and grade of the cancer. In addition, we studied any on-going improvement or decline in the survival for patients with colorectal cancer. We studied this across two time periods, which are 1995-2005 and 2006-2015. The survival time of colon cancer patients was studied from diagnosis time to a specified time. Tests, such as log-rank and chi-squared, logistic regressions, and Cox proportional hazards regressions were utilized to assess survival rates. A 194, 955 population-based colorectal cancer cohort was utilized, which consisted of 67.60% Caucasian, 12.76% African American, 17.52% Hispanic, and the remaining 2.12% of other race. A racial disparity is evident in the survival of CRC patients in Texas given that survival was the lowest for the African American with their hazard ratio being the highest (1.197). This might be due to the diagnosis at a later stage of the disease, as compared to other groups. The other factors studied here too play a role in the survival rates of CRC patients. Patients with Medicaid demonstrated the least survival, with a hazard ratio of 1.131. Age was also significant factor in the survival of CRC patients, since older patients demonstrated lower survival rates. The stage and grade of cancer that indicated the lowest survival was Distant and Grade IV, with Hazards of deaths of 5.389 and 1.218, respectively. Patients who had chemotherapy as treatment had the lowest survival (1.081 hazard of death), while patients who had a surgery as a form of treatment had the highest survival (0.835 hazard of death). A trend with poverty and survival was also discovered. As the poverty index increased, deaths of CRC patients increased as well, which shows decrease in survival. Gender did not play a significant role when determining survival, given that their p-values were non-significant, but males presented a lower survival. Overall, there was a decline in the survival of colorectal cancer patients across both periods before mentioned among the races/ethnicities studied. This study will provide a succinct overview of the disease and the factors responsible for the differential survival rates based on race. Citation Format: Gabriela Chavarria, Demba Fofana, Manish Tripathi. Factors responsible for ethnicity-based survival rates of colorectal cancer patients in the state of Texas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 779.

Risk and severity of SARS-CoV-2 infection in breast cancer patients undergoing a structured infection screening program at the University and Hospital Trust of Verona

In recent years, predictive data mining techniques play a vital role in the field of medical informatics. These techniques help the medical practitioners in predicting various classes which is useful in prediction treatment. One of such major difficulty is prediction of survival rate in breast cancer patients. Breast cancer is a common disease these days and fighting against it is a tough battle for both the surgeons and the patients. To predict the survivability rate in breast cancer patients which helps the medical practitioner to select the type of treatment a predictive data mining technique called Diversified Multiple Decision Tree (DMDT) classification is used. Additionally, to avoid difficulties from the outlier and skewed data, it is also proposed to perform the improvement of training space by outlier filtering and over sampling. As a result, this novel approach gives the survivability rate of the cancer patients based on which the medical practitioners can choose the type of treatment.

Objective To investigate the clinical pathologic characteristics and prognosis of bilateral breast cancer, and to determine whether clinical factors is related to p53 gene mutation. Methods Archival material was reviewed from 48 cases of bilateral breast cancar. The clinical and pathological features of bilateral breast cancer were compared and summarized. Immunohistochemical stains for P53 were performed on 33 cases of bilateral breast cancer, 141 cases of unilateral breast cancer were also examined as control. Results The five-year survival rate for bilateral breast cancer patients was 70.5%. The median age when bilatereral breast cancer first dignosed was 47.5 (range from 27 to 69). The median time interval between the first and the subsequent breast cancer diagnosis was 9.5 months. Invasive ductal breast carcinoma was the main pathologic type of bilateral breast cancer. 88.5% of bilateral breast cancer would have the same estrogen receptor (ER) status and 81.8% would have the same human epidermal growth hormone receptor 2 (HER2) status between the first and secondary primary tumors. Mutation p53 was more common among the bilateral breast cancer patients compared with the unilateral breast cancer patients (45.5% vs. 26.2%, χ2=4.711, P=0.030). There was no difference on the overall survival between bilateral breast cancer with p53(+ ) and p53(-)(χ2=0.434, P=0.510). Conclusion The main pathologic type of bilateral breast cancer is invasive ductal breast carcinoma, there is a good match of the ER and HER2 status between the first breast cancer and the contralateral one. Bilateral breast cancer patients have a similar overall survial with the unilateral breast cancer. p53 mutation is more common among bilateral breast cancer patients than those with unilateral breast cancer. Key words: Breast neoplasms; Pathology, clinical; Genes, p53; Second primary

Aim. To identify population characteristics of the PIK3CA gene mutation among breast cancer patients in the Krasnoyarsk region.Materials and methods. The study included 140 patients with breast cancer with a certain mutation status of the PIK3CA gene, observed at the Krasnoyarsk Regional Clinical Oncology Center named after A.I. Kryzhanovsky. Determination of PIK3CA gene mutations (exons 2, 5, 8, 10 and 21) was carried out using commercial kits on equipment from Roche (Germany). Statistical processing of the obtained data was carried out using Microsoft Excel and Statistica 12 software products. The assessment of the factor of influence on the relapse-free and overall survival was carried out by constructing and comparing Kaplan–Meier curves. The result was considered statistically significant at a significance level of p <0.05.Results and conclusion. The overall frequency of occurrence of PIK3CA gene mutations is 38.6 %. The most common mutations are H1047X (55.4 %) in exon 21 and E545K (27.8 %) in exon 10. The median age of breast cancer patients with mutation status in the PIK3CA gene was 58.9 [49.0; 67.0] years, median time to relapse or progression was 62.2 [27.0; 84.0] months. There were no statistically significant differences in relapse-free survival between the presence and absence of mutations (p = 0.8). The effect of changes in PIK3CA on a decrease in overall survival rates (p = 0.047) in breast cancer patients was shown.

Background Few accurate up-to-date studies provide liver cancer mortality and survival information in Zhejiang province. This research aimed to depict the mortality and survival of liver cancer in Zhejiang province in China during 2005-2010. Methods The data were collected from the Zhejiang Chronic Disease Surveillance Information and Management System, and the mortality rates of liver cancer were calculated by gender, age, and areas. Chinese population census in 2000 and Segi's world population were used for age-standardized mortality rate. The observed and relative survival rates of liver cancer patients were analyzed. Results The crude mortality rate of liver cancer was 32.11/105. The age-standardized mortality rate was 17.39/105 and 23.07/105 by Chinese population (ASIRC) and Segi's world population (ASIRW), respectively. The crude liver cancer mortality rate and age-standardized rate in urban areas were lower than those of rural areas. The overall 1-, 3-, and 5-year observed survival (OS) rates of liver cancer patients were 38.61%, 21.65%, and 16.83%, respectively. The 1-, 3-, and 5-year relative survival (RS) rates of liver cancer patients were 39.49%, 23.27%, and 19.09%, respectively. Survival rate decreased obviously within 1 to 5 years and then leveled off. It was shown that the male overall survival rate was higher than the female one and the difference was statistically significant (P<0.05). Conclusions Both lower mortality and better survival rates were observed in urban areas, compared to rural areas. Relevant parties including government, public resource, and propaganda department should devote enough attention to rural areas.

: PCNA, an essential protein in the DNA synthesis and repair, was shown to be phosphorylated at Y2111 by a nuclear kinase. A consequence of this post-transitional modification has been highly correlated with a reduced survival rate of breast cancer patients. However, no basic of clinical studies have addressed if these inhibitors down-regulate the nuclear function of the protein. The original observations indicated that the EGFR was a major kinase involved in this phosphorylation. Inhibitors of EGFR have exciting potential in treatment but have failed to show clinical efficacy as a mono-therapy treatment option for breast cancer patients. By screening a panel of protein kinase inhibitors in triple negative breast cells for impact on phosphorylation, a direct correlation with EGFR inhibition is not indicated, rather a broader network connecting PCNA modification on chromatin with DNA damage response is implicated. Novel bioconjugates of getfitinib (Iressa) with nuclear targeting peptide-peptoid hybrid sequences have been shown to retain growth inhibitory activity in this context and open avenues for utility in research and new therapies. A new analytical method for enhanced detection of the phosphorylated PCNA isoforms has been shown to be feasible. In addition, by adopting this assay to screen nuclear proteomes of breast tumor cells indicated a more diverse array of PCNA isoforms bearing post-translational modifications opening the door to select specific markers to stage breast cancer patients for molecular therapies.

This study aimed to use non-invasive methods to assess and compare the levels of oxidative indices and non-enzymatic antioxidants in breast and colorectal cancer (CRC) patients. Various studies have reported on lipid peroxidation, hydrogen peroxide (H(2)O(2)) and ferric-reducing antioxidant power (FRAP) levels in the serum of cancer patients but this is the first report that highlights the significance of urinary-advanced oxidative protein product (AOPP) in cancer patients. The levels of advanced oxidative protein product (AOPP), hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA) which is a marker for lipid peroxidation and ferric-reducing antioxidant power (FRAP) were measured in urine samples of breast (n = 101) and colorectal cancer (n = 49) patients attending the Oncology Clinic, University Malaya Medical Centre, Kuala Lumpur and were compared with 95 age-matched healthy individuals. AOPP, H(2)O(2) and MDA levels in the urine were significantly higher in the CRC patients compared to the control subjects and breast cancer patients. In breast cancer patients, only AOPP level was elevated. FRAP level did not differ between breast and colorectal cancer patients but the levels were significantly lower compared to control subjects. Urinary oxidative indices such as AOPP, H(2)O(2), and MDA as well as FRAP could serve as useful non-invasive oxidative stress markers in colorectal cancer but only AOPP serves as a useful urinary oxidative biomarker in breast cancer.

This study addresses the disparity in cancer survival rates among hospitals in Osaka, Japan, Using data from the Osaka Cancer Registry, four‐year survival rates for stomach cancer patients (n=8,845) diagnosed in 1976, 1981 and 1986, and lung cancer (n = 9,795) and breast cancer patients (n= 7,377) diagnosed in 1975–77, 1980–82 and 1985–87 were calculated according to four hospital categories (teaching hospitals, large hospitals: 400+ beds excluding teaching hospitals, medium‐size hospitals: 150–399 beds, and small hospitals: 20–149 beds). Cox's proportional hazards model was employed with adjustment for sex, age, clinical stage at diagnosis, and treatment status. Stomach and lung cancer patients treated in large, medium‐size and small hospitals showed significantly higher risks of death than those treated in teaching hospitals in 1975–87. Interhospital differences in breast cancer survival appeared to increase in 1975–87, whereas those in stomach and lung cancer survivals decreased during the same period.