scholarly journals Role of Genetic Variation in ABC Transporters in Breast Cancer Prognosis and Therapy Response

2020 ◽  
Vol 21 (24) ◽  
pp. 9556
Author(s):  
Viktor Hlaváč ◽  
Radka Václavíková ◽  
Veronika Brynychová ◽  
Renata Koževnikovová ◽  
Katerina Kopečková ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Variation ◽  
Abc Transporters ◽  
Statistical Significance ◽  
Strong Support ◽  
Disease Free Survival ◽  
Cancer Prognosis ◽  
Future Research ◽  
Regulatory Sequences

Breast cancer is the most common cancer in women in the world. The role of germline genetic variability in ATP-binding cassette (ABC) transporters in cancer chemoresistance and prognosis still needs to be elucidated. We used next-generation sequencing to assess associations of germline variants in coding and regulatory sequences of all human ABC genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 43 prioritized variants associating with response or survival in the above testing phase were then analyzed by allelic discrimination in the large validation set (n = 802). Variants in ABCA4, ABCA9, ABCA12, ABCB5, ABCC5, ABCC8, ABCC11, and ABCD4 associated with response and variants in ABCA7, ABCA13, ABCC4, and ABCG8 with survival of the patients. No association passed a false discovery rate test, however, the rs17822931 (Gly180Arg) in ABCC11, associating with response, and the synonymous rs17548783 in ABCA13 (survival) have a strong support in the literature and are, thus, interesting for further research. Although replicated associations have not reached robust statistical significance, the role of ABC transporters in breast cancer should not be ruled out. Future research and careful validation of findings will be essential for assessment of genetic variation which was not in the focus of this study, e.g., non-coding sequences, copy numbers, and structural variations together with somatic mutations.

scholarly journals Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response

2021 ◽  
Vol 22 (6) ◽  
pp. 2826
Author(s):  
Viktor Hlaváč ◽  
Radka Václavíková ◽  
Veronika Brynychová ◽  
Pavel Ostašov ◽  
Renata Koževnikovová ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Variation ◽  
Cytochromes P450 ◽  
Disease Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Free Survival ◽  
Disease Free

Breast cancer is the most frequent cancer in the female population worldwide. The role of germline genetic variability in cytochromes P450 (CYP) in breast cancer prognosis and individualized therapy awaits detailed elucidation. In the present study, we used the next-generation sequencing to assess associations of germline variants in the coding and regulatory sequences of all human CYP genes with response of the patients to the neoadjuvant cytotoxic chemotherapy and disease-free survival (n = 105). A total of 22 prioritized variants associating with a response or survival in the above evaluation phase were then analyzed by allelic discrimination in the large confirmation set (n = 802). Associations of variants in CYP1B1, CYP4F12, CYP4X1, and TBXAS1 with the response to the neoadjuvant cytotoxic chemotherapy were replicated by the confirmation phase. However, just association of variant rs17102977 in CYP4X1 passed the correction for multiple testing and can be considered clinically and statistically validated. Replicated associations for variants in CYP4X1, CYP24A1, and CYP26B1 with disease-free survival of all patients or patients stratified to subgroups according to therapy type have not passed a false discovery rate test. Although statistically not confirmed by the present study, the role of CYP genes in breast cancer prognosis should not be ruled out. In conclusion, the present study brings replicated association of variant rs17102977 in CYP4X1 with the response of patients to the neoadjuvant cytotoxic chemotherapy and warrants further research of genetic variation CYPs in breast cancer.

scholarly journals The role of ferroptosis in breast cancer patients: a comprehensive analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Hong Yu ◽  
Hua-Dong Li
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Function Analysis ◽  
Cancer Prognosis ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
Cell Functions

AbstractBreast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.

scholarly journals Role of n-3 Polyunsaturated Fatty Acids and Exercise in Breast Cancer Prevention: Identifying Common Targets

2016 ◽  
Vol 9 ◽  
pp. NMI.S39043 ◽  
Author(s):  
Salma A. Abdelmagid ◽  
Jessica L. MacKinnon ◽  
Sarah M. Janssen ◽  
David W.L. Ma
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Cancer Prevention ◽  
Breast Cancer Prevention ◽  
Future Research ◽  
Pufa Intake ◽  
Diet And Exercise ◽  
Important Study

Diet and exercise are recognized as important lifestyle factors that significantly influence breast cancer risk. In particular, dietary n-3 polyunsaturated fatty acids (PUFAs) have been shown to play an important role in breast cancer prevention. Growing evidence also demonstrates a role for exercise in cancer and chronic disease prevention. However, the potential synergistic effect of n-3 PUFA intake and exercise is yet to be determined. This review explores targets for breast cancer prevention that are common between n-3 PUFA intake and exercise and that may be important study outcomes for future research investigating the combined effect of n-3 PUFA intake and exercise. These lines of evidence highlight potential new avenues for research and strategies for breast cancer prevention.

Advances in Adjuvant Endocrine Therapy for Postmenopausal Women

2008 ◽  
Vol 26 (5) ◽  
pp. 798-805 ◽  
Author(s):  
Nancy U. Lin ◽  
Eric P. Winer
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Diagnosis ◽  
Endocrine Treatment ◽  
Future Research ◽  
Sequential Approach ◽  
Hormone Receptor Positive

Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity.

Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study.

1991 ◽  
Vol 9 (7) ◽  
pp. 1113-1123 ◽  
Author(s):  
D F Hayes ◽  
R Mesa-Tejada ◽  
L D Papsidero ◽  
G A Croghan ◽  
A H Korzun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Weight ◽  
Monoclonal Antibodies ◽  
High Molecular Weight ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Immunoperoxidase Staining ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Axillary Lymph Node Metastases

Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.

G8 as a screening tool for comprehensive geriatric assessment in patients with breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24010-e24010
Author(s):  
Rocio Grajales ◽  
Alicia Gutierrez Mata ◽  
José Enrique Martínez Hernández ◽  
Alejandro Zavala-Calderon
Keyword(s):  
Breast Cancer ◽  
Geriatric Assessment ◽  
Comprehensive Geriatric Assessment ◽  
Screening Tool ◽  
Statistical Significance ◽  
Clinical Stage ◽  
Disease Free Survival ◽  
Rank Test ◽  
Spearman Correlation ◽  
Geriatric Screening

e24010 Background: G8 is a geriatric screening tool designed to identify elderly cancer patients who benefit from a comprehensive geriatric assessment (CGA). Despite the increase in the incidence of cancer in the geriatric patients, there is absence of trials targeting this population. Decisions are often made based on their age and ECOG/Karnofsky scales, which does not reflect the actual role of an elderly patient. It is necessary to identify patients who require a CGA for an accurate evaluation and optimal oncological management. The routine implementation of the G8 geriatric screening tool in the oncology consultation consumes little time and is useful for timely referral of vulnerable patients to specialized care, in order to generate a positive impact on oncological therapy decision-making, improving their outcomes. Our main objective was to determine, using the geriatric screening tool G8, the percentage of patients aged >65 years with breast cancer, which require a CGA. Methods: The G8 questionnaire was applied to patients >65 yo with a diagnosis of breast cancer from December 2019 to May 2020. The baseline characteristics were prospectively collected and included clinical and demographic characteristics. The prognostic value of the functional status of the ECOG was evaluated and compared with that obtained from the G8. The difference between groups was assessed using Pearson's chi square with Yates correction. Additional scores were calculated using the Kaplan-Meier method and compared between groups using the log rank test. The hazard ratio with a 95% confidence interval was estimated using a Cox proportional hazards analysis, considering an abnormal G8 score as an exposure variable. Spearman correlation was made between age and the G8 score obtained. SPSS v22 software (IBM, USA) was used for all analyzes. Results: From December 2019 to May 2020, 357 patients were recruited. The mean age was 73.57 years (SD+7.02 y). The most frequent clinical stage was IIA (27.7%), followed by I (21.8%). 74.2% had an ECOG 1. Regarding treatment, 317 patients (88.8%) were on hormone therapy. The percentage of patients requiring a CGA was 44.3% (n = 158), of which only 55.1% (n = 87) were performed. We found no significant association between the requirement of CGA and clinical stage (p = 0.27) or treatment received (p = 0.345); but according to the ECOG, we obtained statistical significance p < 0.0001. Spearman correlation was performed between age and the G8 score, a correlation of 0.422 was obtained with p < 0.0001.The most affected domains of G8 were polypharmacy (51%) and ingestion (28.3%). Disease-free survival analysis was performed, without finding differences between vulnerable-frail and healthy patients. Conclusions: The G8 is a tool that allows to discern which patients require a CGA, in order to carry out interventions to improve comprehensive cancer treatment, so it should be implemented routinely in the oncology consultation.

scholarly journals Health care use and remaining needs for support among women with breast cancer in the first 15 months after diagnosis: the role of the GP

2019 ◽  
Vol 37 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Deborah N Lo-Fo-Wong ◽  
Hanneke C de Haes ◽  
Neil K Aaronson ◽  
Doris L van Abbema ◽  
Jolien M Admiraal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
General Practice ◽  
Treatment Phase ◽  
Health Care Use ◽  
Future Research ◽  
Frequent Contact ◽  
Health Care Practices ◽  
Additional Support

Abstract Background The number of women with breast cancer in general practice is rising. To address their needs and wishes for a referral, GPs might benefit from more insight into women’s health care practices and need for additional support. Objective To examine the prevalence of health care use and remaining needs among women with breast cancer in the first 15 months after diagnosis. Methods In this multicentre, prospective, observational study women with breast cancer completed a questionnaire at 6 and 15 months post-diagnosis. Medical data were retrieved through chart reviews. The prevalence of types of health care used and remaining needs related to medical, psychosocial, paramedical and supplementary service care (such as home care), was examined with descriptive analyses. Results Seven hundred forty-six women completed both questionnaires. At both assessments patients reported that they had most frequent contact with medical and paramedical providers, independent of types of treatment received. Three to fifteen percent of the patients expressed a need for more support. Prominent needs included a wish for more frequent contact with a physiotherapist, a clinical geneticist and a psychologist. Patients also wanted more help for chores around the house, particularly in the early post-treatment phase. Conclusion A small but relevant percentage of women with breast cancer report having unmet needs. GPs may need to be particularly watchful of their need for more support from specific providers. Future research into the necessity of structural needs assessment among cancer patients in general practice is warranted.

scholarly journals The Role of Interpersonal Influence in Counterbalancing Psychopathic Personality Trait Facets at Work

2016 ◽  
Vol 44 (4) ◽  
pp. 1338-1368 ◽  
Author(s):  
Nora Schütte ◽  
Gerhard Blickle ◽  
Rachel E. Frieder ◽  
Andreas Wihler ◽  
Florian Schnitzler ◽  
...  
Keyword(s):  
Strong Support ◽  
Counterproductive Work Behavior ◽  
Work Behavior ◽  
Psychopathic Personality ◽  
Future Research ◽  
Interpersonal Influence ◽  
Interpersonal Performance ◽  
Low Levels ◽  
Differential Relations

The purpose of this study was to examine the relations of two facets of psychopathic personality (i.e., self-centered impulsivity and fearless dominance) with interpersonally directed counterproductive work behavior (CWB-I) and contextual performance (CP). Consistent with research on psychopathy, our hypothesis suggested that self-centered impulsivity (i.e., behavioral impulsivity characterized by disregard for rules and responsibilities) would be positively related to CWB-I and negatively related to CP. Using socioanalytic theory, we further suggested that fearless dominance (i.e., an egotistical personal style characterized by self-promotion and prioritization of one’s own needs before those of others) would be negatively associated with interpersonal performance (i.e., high CWB-I and low CP) only when individuals indicated low levels of interpersonal influence (i.e., a dimension of political skill reflecting an ability to adapt one’s behavior in subtle, sophisticated, and situationally effective ways). Results provided strong support for the differential relations of the psychopathic personality dimensions with the criteria of interest. Implications for theory, practice, and future research are provided in light of a number of notable strengths and limitations.

scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

Prognostic Role of Estrogen Receptor Determination in Breast Cancer

1983 ◽  
Vol 69 (6) ◽  
pp. 527-530 ◽  
Author(s):  
Stefano Ciatto ◽  
Patrizia Bravetti ◽  
Gaetano Cardona ◽  
Luigi Cataliotti ◽  
Roberto Crescioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recent Literature ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Prognostic Role ◽  
Free Survival ◽  
The Difference ◽  
Disease Free ◽  
Actuarial Method

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N– cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N– cases should be reconsidered.

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