scholarly journals The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 727
Author(s):  
Luigia Stefania Stucci ◽  
Valeria Internò ◽  
Marco Tucci ◽  
Martina Perrone ◽  
Francesco Mannavola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ataxia Telangiectasia ◽  
Cell Cycle Control ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Telomere Maintenance ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Atm Gene ◽  
Metastatic Involvement

Molecular alterations of the Ataxia-telangiectasia (AT) gene are frequently detected in breast cancer (BC), with an incidence ranging up to 40%. The mutated form, the Ataxia-telangiectasia mutated (ATM) gene, is involved in cell cycle control, apoptosis, oxidative stress, and telomere maintenance, and its role as a risk factor for cancer development is well established. Recent studies have confirmed that some variants of ATM are associated with an increased risk of BC development and a worse prognosis. Thus, many patients harboring ATM mutations develop intermediate- and high-grade disease, and there is a higher rate of lymph node metastatic involvement. The evidence concerning a correlation of ATM gene mutations and the efficacy of therapeutic strategies in BC management are controversial. In fact, ATM mutations may sensitize cancer cells to platinum-derived drugs, as BRCA1/2 mutations do, whereas their implications in objective responses to hormonal therapy or target-based agents are not well defined. Herein, we conducted a review of the role of ATM gene mutations in BC development, prognosis, and different treatment strategies.

scholarly journals Sex Differences in Patients With Occult Cancer After Venous Thromboembolism

2017 ◽  
Vol 24 (3) ◽  
pp. 489-495 ◽  
Author(s):  
Luis Jara-Palomares ◽  
Remedios Otero ◽  
David Jiménez ◽  
Juan Manuel Praena-Fernández ◽  
Agustina Rivas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sex Differences ◽  
Venous Thromboembolism ◽  
Clinical Characteristics ◽  
Treatment Strategies ◽  
Common Cancer ◽  
Occult Cancer ◽  
Increased Risk ◽  
Male Sex ◽  
Increasing Risk

In patients with venous thromboembolism (VTE), male sex has been associated with an increased risk of occult cancer. The influence of sex on clinical characteristics, treatment, cancer sites, and outcome has not been thoroughly investigated yet. We used the Registro Informatizado Enfermedad TromboEmbólica registry to compare the clinical characteristics, treatment strategies, cancer sites, and clinical outcomes in patients with VTE having occult cancer, according to sex. As of June 2014, 5864 patients were recruited, of whom 444 (7.6%; 95% confidence interval: 6.8-8.2) had occult cancer. Of these, 246 (55%) were men. Median time elapsed from VTE to occult cancer was 4 months (interquartile range: 2-8.4), with no sex differences. Women were older, weighed less, and were less likely to have chronic lung disease than men. The most common cancer sites were the lung (n = 63), prostate (n = 42), and colorectal (n = 29) in men and colorectal (n = 38), breast (n = 23), uterine (n = 18), hematologic (n = 17), or pancreas (n = 15) in women. Men were more likely to have lung cancer than women (2.18% vs 0.30%; P < .01) and less likely to have pancreatic cancer (0.17% vs 0.5%; P = .03). Interestingly, breast cancer was more likely found in women aged ≥50 years than in those aged <50 years (0.97% vs 0.14%; P = .03). This study highlights the existence of sex differences in patients with VTE having occult cancer. One in every 2 men had lung, prostate, or colorectal cancer. In women, there is a heterogeneity of cancer sites, increasing risk of breast cancer in those aged >50 years.

scholarly journals ATAXIA-TELANGIECTASIA (LOUIS-BAR SYNDROME): REPORT OF A CASE

2019 ◽  
pp. 7-10
Author(s):  
O.Y. Bogacheva ◽  
V.I. Fomichev
Keyword(s):  
Ataxia Telangiectasia ◽  
Genetic Disorder ◽  
Final Diagnosis ◽  
Diagnostic Process ◽  
Laboratory Findings ◽  
Humoral Immunodeficiency ◽  
Increased Risk ◽  
The Face ◽  
Atm Gene ◽  
The Brain

Ataxia-telangiectasia is a rare genetic disorder with multisystem manifestations. Major symptoms include development of ataxia and oculomotor disorders in early childhood. Telangiectasias may appear at the same period of time or later that is more often. They are typically located on the conjunctiva and on the face. In the vast majority of patients, primary cell-humoral immunodeficiency is observed. Repeated and protracted infectious diseases are typical. Patients often develop chronic respiratory disorders. They also have an increased risk of malignancies. Laboratory findings usually include an increase in the level of alpha-fetoprotein and impaired immunological status: a decrease in T- and B- lymphocytes counts, and also a decrease in the levels of IgA, IgG, IgE. MRI of the brain shows signs of atrophy of the cerebellar vermis and hemispheres, which become more pronounced at a later age. The final diagnosis is made on the basis of the results of genetic testing, when mutations of the ATM gene are detected. The typical course of the disease and the steps of the diagnostic process are illustrated by our own clinical observation.

scholarly journals Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Amelie Schramm ◽  
Nikolaus De Gregorio ◽  
Peter Widschwendter ◽  
Visnja Fink ◽  
Jens Huober
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Increased Risk ◽  
Positive Breast Cancer

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.

scholarly journals Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Enea Gino Di Domenico ◽  
Elena Romano ◽  
Paola Del Porto ◽  
Fiorentina Ascenzioni
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Genome Stability ◽  
Genetic Disorder ◽  
Cell Cycle Control ◽  
Premature Aging ◽  
Telomere Maintenance ◽  
Damage Response

The mammalian protein kinase ataxia telangiectasia mutated (ATM) is a key regulator of the DNA double-strand-break response and belongs to the evolutionary conserved phosphatidylinositol-3-kinase-related protein kinases. ATM deficiency causes ataxia telangiectasia (AT), a genetic disorder that is characterized by premature aging, cerebellar neuropathy, immunodeficiency, and predisposition to cancer. AT cells show defects in the DNA damage-response pathway, cell-cycle control, and telomere maintenance and length regulation. Likewise, inSaccharomyces cerevisiae, haploid strains defective in theTEL1gene, the ATM ortholog, show chromosomal aberrations and short telomeres. In this review, we outline the complex role of ATM/Tel1 in maintaining genomic stability through its control of numerous aspects of cellular survival. In particular, we describe how ATM/Tel1 participates in the signal transduction pathways elicited by DNA damage and in telomere homeostasis and its importance as a barrier to cancer development.

scholarly journals ATM gene mutations in sporadic breast cancer patients from Brazil

SpringerPlus ◽  
2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Flavia Rotea Mangone ◽  
Elisabete C Miracca ◽  
Harriet E Feilotter ◽  
Lois M Mulligan ◽  
Maria Aparecida Nagai
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Sporadic Breast Cancer ◽  
Gene Mutations ◽  
Breast Cancer Patients ◽  
Atm Gene

Ataxia-Telangiectasia genes and breast cancer risk in a French family study

2005 ◽  
Vol 72 (S1) ◽  
pp. 73-80 ◽  
Author(s):  
Nadine Andrieu ◽  
Eve Cavaciuti ◽  
Anthony Laugé ◽  
Katia Ossian ◽  
Nicolas Janin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ataxia Telangiectasia ◽  
Screening Program ◽  
Neuronal Degeneration ◽  
Carrier Status ◽  
X Rays ◽  
Increased Risk ◽  
Exogenous Factors ◽  
Atm Protein ◽  
Risk Of Cancer

Ataxia-telangiectasia (AT) is a rare autosomal recessive early childhood disorder, characterized by progressive neuronal degeneration, immunological deficiency, radiosensitivity and an increased risk of cancer caused in most cases by mutations in the AT-mutated gene (ATM). Epidemiological studies on AT families have shown that AT heterozygous women have an increased risk of developing breast cancer (BC). The ATM protein plays a central role in the recognition and repair of DNA double-strand breaks and the subsequent activation of cell-cycle checkpoints. Whilst AT is a rare disease, 0·5–1% of the general population are estimated to be AT mutation carriers, thus any increases in the risks of cancer associated with ATM carrier status are of public health relevance. The main results of our published studies on the risk of BC in 34 French AT families according to heterozygote status, type of ATM mutation and exogenous factors are summarized here. The risk of BC was higher in ATM heterozygous (HetATM) women and did not differ significantly according to the type of ATM mutation (missense vs truncating) carried by the AT family members but appeared associated with the position of some truncating mutations in certain binding domains of the ATM protein. The effect of exogenous factors, such as reproductive life factors and exposure to ionizing radiation, on the risk of BC according to ATM heterozygote status was assessed. There was no evidence for interaction (except for age at first full-term pregnancy). These findings does not appear to justify a separate screening program from that already available to other women with a first-degree relative affected by BC, as their risks have similar amplitude. Chest X-rays did not appear to be a risk factor for BC in our study population. More powerful studies, using data sets pooled from international sources are being set up to confirm these observations.

scholarly journals Fasting C-Peptide Levels and Death Resulting From All Causes and Breast Cancer: The Health, Eating, Activity, and Lifestyle Study

2011 ◽  
Vol 29 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Melinda L. Irwin ◽  
Catherine Duggan ◽  
Ching-Yun Wang ◽  
Ashley Wilder Smith ◽  
Anne McTiernan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Cox Regression ◽  
Treatment Strategies ◽  
Breast Cancer Diagnosis ◽  
C Peptide ◽  
Risk Of Death ◽  
Increased Risk ◽  
Health Eating

Purpose To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer. Patients and Methods This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses. Results Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m2, women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive. Conclusion Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored.

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