domingo, 13 de agosto de 2017

Massive study launched to test personalized approach to breast cancer screening | University of California

Massive study launched to test personalized approach to breast cancer screening | University of California



Massive study launched to test personalized approach to breast cancer screening

BRCA population screening for predicting breast cancer: for or against?

BRCA population screening for predicting breast cancer: for or against?









BRCA population screening for predicting breast cancer: for or against?

Cancer at Baseline Screening in Patients With Li-Fraumeni Syndrome - The ASCO Post

Cancer at Baseline Screening in Patients With Li-Fraumeni Syndrome - The ASCO Post



Cancer at Baseline Screening in Patients With Li-Fraumeni Syndrome

Surveillance of Dutch Patients With Li-Fraumeni Syndrome: The LiFe-Guard Study. - PubMed - NCBI

Surveillance of Dutch Patients With Li-Fraumeni Syndrome: The LiFe-Guard Study. - PubMed - NCBI



 2017 Aug 3. doi: 10.1001/jamaoncol.2017.1346. [Epub ahead of print]

Surveillance of Dutch Patients With Li-Fraumeni Syndrome: The LiFe-Guard Study.


PMID:
 
28772294
 
DOI:
 
10.1001/jamaoncol.2017.1346

Cancer Genetic Counseling and Testing: Perspectives of Epithelial Ovarian Cancer Patients and Gynecologic Oncology Healthcare Providers. - PubMed - NCBI

Cancer Genetic Counseling and Testing: Perspectives of Epithelial Ovarian Cancer Patients and Gynecologic Oncology Healthcare Providers. - PubMed - NCBI



 2017 Aug 7. doi: 10.1007/s10897-017-0135-2. [Epub ahead of print]

Cancer Genetic Counseling and Testing: Perspectives of Epithelial Ovarian Cancer Patients and Gynecologic Oncology Healthcare Providers.

Abstract

Multi-gene panel testing has expanded the genetic information available to cancer patients. The objective was to assess provider behaviors and attitudes and patient knowledge and attitudes towards genetic counseling and testing. An online survey was distributed to Society of Gynecologic Oncology members and a written questionnaire was administered to patients diagnosed with epithelial ovarian cancer at a tertiary care referral center. Most of the 233 (18% response rate) provider respondents were gynecologic oncologists. Access to a genetic counselor was reported by 87% of providers and 55% deferred all testing to genetic counselors. Of 53 ovarian cancer patient respondents, two-thirds had previously seen a genetic counselor or undergone testing. Patients' attitudes about genetic counseling and/or testing were favorable with respect to themselves (70-81%) and their family members (94%). Less than 25% of patients indicated worrying about health care discrimination, lack of privacy, or high cost. Seventy-seven percent of patients demonstrated a desire to obtain genetic information even if the results were not currently actionable, and 20% of providers stated they test for only those genes with guideline-supported actionable results. Provider practice differences were identified in screening and prevention strategies for patients with deleterious non-BRCA mutations and variants of uncertain significance. The variation in clinical interpretation of results associated with poorly defined cancer risks signals a need for more comprehensive training and guidelines to ensure access to evidence-based care.

KEYWORDS:

Genetic counseling; Genetic testing; Moderate penetrance gene; Ovarian cancer; Panel testing; Variant of uncertain significance

PMID:
 
28785836
 
DOI:
 
10.1007/s10897-017-0135-2

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test. - PubMed - NCBI

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test. - PubMed - NCBI



 2017 Aug 8. doi: 10.1002/cncr.30893. [Epub ahead of print]

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

Abstract

BACKGROUND:

Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer.

METHODS:

The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test.

RESULTS:

Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer.

CONCLUSIONS:

Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017. © 2017 American Cancer Society.

KEYWORDS:

age of onset; early diagnosis; genetic testing; hereditary; kidney neoplasms; neoplastic syndromes

PMID:
 
28787086
 
DOI:
 
10.1002/cncr.30893

Telomeres and telomerase in prostate cancer development and therapy. - PubMed - NCBI

Telomeres and telomerase in prostate cancer development and therapy. - PubMed - NCBI



 2017 Jul 4. doi: 10.1038/nrurol.2017.104. [Epub ahead of print]

Telomeres and telomerase in prostate cancer development and therapy.

Abstract

Aberrations in telomere biology are among the earliest events in prostate cancer tumorigenesis and continue during tumour progression. Substantial telomere shortening occurs in prostate cancer cells and high-grade prostatic intraepithelial neoplasia. Not all mechanisms of telomere shortening are understood, but oxidative stress from local inflammation might accelerate prostatic telomere loss. Critically short telomeres can drive the accumulation of tumour-promoting genomic alterations; however, continued telomere erosion is unsustainable and must be mitigated to ensure cancer cell survival and unlimited replication potential. Prostate cancers predominantly maintain telomeres by activating telomerase, but alternative mechanisms of telomere extension can occur in metastatic disease. Telomerase activity and telomere length assessment might be useful in prostate cancer diagnosis and prognosis. Telomere shortening in normal stromal cells has been associated with prostate cancer, whereas variable telomere lengths in prostate cancer cells and telomere shortening in cancer-associated stromal cells correlated with lethal disease. Single-agent telomerase-targeted treatments for solid cancers were ineffective in clinical trials but have not been investigated in prostate cancer and might be useful in combination with established regimens. Telomere-directed strategies have not been explored as extensively. Telomere deprotection strategies have the advantage of being effective in both telomerase-dependent and telomerase-independent cancers. Disruption of androgen receptor function in prostate cancer cells results in telomere dysfunction, indicating telomeres and telomerase as potential therapeutic targets in prostate cancer.

PMID:
 
28675175
 
DOI:
 
10.1038/nrurol.2017.104

Genomics in Primary and Secondary Prevention of Pancreatic Cancer. - PubMed - NCBI

Genomics in Primary and Secondary Prevention of Pancreatic Cancer. - PubMed - NCBI



 2017 Jul 8. doi: 10.1159/000477234. [Epub ahead of print]

Genomics in Primary and Secondary Prevention of Pancreatic Cancer.

Abstract

BACKGROUND:

Pancreatic cancer (PC) is one of the deadliest cancers worldwide for which little clinical progress has been made in the last decades. Furthermore, increased trends of PC mortality rates have been reported in Westernised countries. PC is usually diagnosed in advanced stages, precluding patients of an effective treatment. Identifying high-risk populations and early detection markers is the first and crucial step to impact on these figures and change the PC horizon.

AIMS/OBJECTIVES:

To discuss the published body of evidence on host and tumor genomics promising markers for primary and/or secondary personalised PC prevention, as well as the future perspectives in the field.

METHODS:

A review of the literature was performed to identify germline and tumor DNA and RNA markers that showed potential usefulness in defining the high-risk population, diagnosing the disease early, and identifying new carcinogens associated with PC.

RESULTS:

Only high-penetrance inherited mutations are used, at present, to define the high-risk PC population. Although there are some promising genomics markers to be used as early detection tests, none has been validated adequately to be integrated into the clinics routine.

CONCLUSIONS:

Despite of important efforts made in the recent time, little progress has been made to better characterise high-risk PC populations and to identify genomics-based markers for its early diagnosis. PC rates continue to rise, and this disease is becoming a real public health problem in the Westernised world. International and multidisciplinary strategies to identify new markers and properly validate the promising ones are urgently needed to implement cost-efficient primary and secondary prevention interventions in PC.

KEYWORDS:

DNA methylation; DNA mutations; Genetic variants; Genomics; Pancreatic cancer; Primary prevention; RNA expression; Risk prediction score; Screening; Secondary prevention

PMID:
 
28689205
 
DOI:
 
10.1159/000477234

NCI study shows feasibility of cancer screening protocol for Li-Fraumeni syndrome patients - Scienmag: Latest Science and Health News

NCI study shows feasibility of cancer screening protocol for Li-Fraumeni syndrome patients - Scienmag: Latest Science and Health News



NCI Study Shows Feasibility Of Cancer Screening Protocol For Li-Fraumeni Syndrome Patients

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In a new study from the National Cancer Institute (NCI), part of the National Institutes of Health, researchers found a higher than expected prevalence of cancer at baseline screening in individuals with Li-Fraumeni syndrome (LFS), a rare inherited disorder that leads to a higher risk of developing certain cancers. The research demonstrates the feasibility of a new, comprehensive cancer screening protocol for this high-risk population.
The study was led by Sharon A. Savage, M.D., of NCI's Division of Cancer Epidemiology and Genetics (DCEG), and was published with a companion meta-analysis on August 3, 2017, in JAMA Oncology.

Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. - PubMed - NCBI

Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. - PubMed - NCBI



 2017 Jun 1;23(11):e38-e45. doi: 10.1158/1078-0432.CCR-17-0408.

Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome.

Abstract

Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited condition caused by germline mutations of the TP53 tumor suppressor gene encoding p53, a transcription factor triggered as a protective cellular mechanism against different stressors. Loss of p53 function renders affected individuals highly susceptible to a broad range of solid and hematologic cancers. It has recently become evident that children and adults with LFS benefit from intensive surveillance aimed at early tumor detection. In October 2016, the American Association for Cancer Research held a meeting of international LFS experts to evaluate the current knowledge on LFS and propose consensus surveillance recommendations. Herein, we briefly summarize clinical and genetic aspects of this aggressive cancer predisposition syndrome. In addition, the expert panel concludes that there are sufficient existing data to recommend that all patients with LFS be offered cancer surveillance as soon as the clinical or molecular LFS diagnosis is established. Specifically, the panel recommends adoption of a modified version of the "Toronto protocol" that includes a combination of physical exams, blood tests, and imaging. The panel also recommends that further research be promoted to explore the feasibility and effectiveness of these risk-adapted surveillance and cancer prevention strategies while addressing the psychosocial needs of individuals and families with LFS. Clin Cancer Res; 23(11); e38-e45. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

PMID:
 
28572266
 
DOI:
 
10.1158/1078-0432.CCR-17-0408