domingo, 24 de septiembre de 2017

Perspectives of Women Considering Bilateral Prophylactic Mastectomy and their Peers towards a Telephone-Based Peer Support Intervention. - PubMed - NCBI

Perspectives of Women Considering Bilateral Prophylactic Mastectomy and their Peers towards a Telephone-Based Peer Support Intervention. - PubMed - NCBI



 2017 Sep 15. doi: 10.1007/s10897-017-0148-x. [Epub ahead of print]

Perspectives of Women Considering Bilateral Prophylactic Mastectomy and their Peers towards a Telephone-Based Peer Support Intervention.

St-Pierre D1,2,3Bouchard K2,3Gauthier L2,3,4Chiquette J2,3,4,5Dorval M6,7,8,9,10Centre ROSE.

Abstract

Prophylactic mastectomy is an effective strategy to reduce the risk of breast cancer for women carrying a BRCA1/2 germline mutation. This decision is complex and may raise various concerns. Women considering this surgery have reported their desire to discuss the implications of this procedure with women who have undergone prophylactic mastectomy. We conducted a qualitative study to describe the topics covered during a telephone-based peer support intervention between women considering prophylactic mastectomy (recipients) and women who had undergone this surgery (peers), and to explore their perspectives regarding the intervention. Thirteen dyads were formed and data from participant logbooks and evaluation questionnaires were analyzed using a thematic content analysis. Three main dimensions emerged: physical, psychological, and social. The most frequent topics discussed were: surgery (92%), recovery (77%), pain and physical comfort (69%), impacts on intimacy and sexuality (54%), cancer-related anxiety (54%), experience related to loss of breasts (46%). Peers and recipients report that sharing experiences and thoughts about prophylactic mastectomy and the sense of mutual support within the dyad contributed significantly to their satisfaction. Special attention should be paid to the similarities between personal and medical profiles in order to create harmonious matches.

KEYWORDS:

BRCA1/2; Genetic counseling; Hereditary breast and ovarian cancer syndrome; Peer support; Prophylactic mastectomy

PMID:
 
28916957
 
DOI:
 
10.1007/s10897-017-0148-x

Integrating genomics into population-based cancer surveillance in the era of precision medicine | | Blogs | CDC

Integrating genomics into population-based cancer surveillance in the era of precision medicine | | Blogs | CDC

Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People

Integrating genomics into population-based cancer surveillance in the era of precision medicine

Posted on  by Muin J. Khoury, Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia and Lynne Penberthy, Division of Cancer Control and Population Sciences, National Cancer Institute

individuals all over a map of the US with DNA and a magnifiying glass on one person



Population-based cancer surveillance provides a quantitative measurement of cancer occurrence in the United States and globally. Core activities of surveillance include measuring cancer incidence and characterizing each cancer with regard to histopathology, stage, and treatment in the context of survival. Cancer surveillance has been crucial in informing policy and practice, as well as clinical and public health efforts to reduce the cancer burden. Surveillance also provides information for generating research hypotheses on cancer causes and outcomes, and for developing and evaluating interventions for cancer prevention and treatment.
Cancer surveillance traditionally is conducted based on tumor anatomic location, histologic features, size, involvement of lymph nodes and distant metastasis (i.e., anatomic stage) at diagnosis. However, within and across cancers, biomarkers can identify heterogeneous subgroups associated with different risk factors, treatment responses, recurrences and survival patterns. Population-based cancer registries have already been integrating these important predictive and prognostic factors into data collections. Some of these go into anatomic stage determination (e.g. Gleason score and prostate specific antigen) others such as gene expression profiling for breast cancer are used to predict response to therapy and guide treatment decisions. However, there are many new biomarkers that have been incorporated into the AJCC 8th Edition as a component of prognostic stage and will be collected starting in January 2018, if they are not already part of routine surveillance (such as breast cancer gene expression profiling and human papilloma virus). The use of these biomarkers in refining surveillance data is increasingly important. For example, the 2015 annual report showed breast cancer incidence by molecular subtypes using tumor biomarkers for hormone receptor (HR) and human growth factor-neu receptor (HER2) expression. The report showed that HR+/HER2- breast cancers, the subtype with the best prognosis, were the most common with highest rates among non-Hispanic white women, local stage cases, and low poverty areas. HR+/HER2- breast cancer incidence rates were strongly correlated with mammography use, especially among non-Hispanic white women. Triple-negative breast cancers, the subtype with the worst prognosis, were highest among non-Hispanic black women.
The surveillance community must continue to evolve in their characterization of cancers according to biomarkers for subtype classifications. With rapidly evolving clinical applications in sequencing of the human genome as well as the genomes of tumors, the traditional anatomic descriptions of cancer types will be supplemented by molecular classification based on tumor genetic aberrations. Other tumor-related genome markers are rapidly maturing providing prognostic indicators for survival and response to therapy (e.g. gene expression profiling in prostate cancer). In addition, conducting surveillance for inherited causes of cancer, which account for about 5-10% of all cancers, will allow us to stratify reporting and tracking of cancers by underlying genetic causes. Examples include inherited mutations in BRCA1/2 in breast and ovarian cancer, and mutations in mismatch repair genes (Lynch syndrome) in colorectal and endometrial cancer.
Patients with inherited cancers can also respond differently to different treaments and may have different outcomes. (see one example here)  Such integration will allow monitoring of incidence, response to treatments and survivorship, evaluating trends and uncovering gaps in interventions across subgroups of heterogeneous cancer types and subgroups of the population based on age, race/ethnicity, geographic locations and other factors. The NCI’s Surveillance, Epidemiology, and End Results (SEER) cancer surveillance program is currently supporting an important pilot in which BRCA mutation panels have been linked to breast and ovarian cancer cases in California and Georgia. This linkage represents the first population-based set of information on testing of women with breast and ovarian cancer. This type of linkage exemplifies the new approaches that can improve cancer surveillance in today’s rapidly evolving oncology practice.
The launch of the U.S. Precision Medicine initiative in 2015 includes a large cancer component, featuring acceleration of NCI precision medicinetrials. These efforts, will, over time, lead to molecularly targeted interventions that maximize benefits and minimize harms and costs of interventions. A conceptual shift toward precision medicine has the potential to change diagnostic categories, treatment strategies, and enable early detection and prevention. The approach has led to some new treatments that are individually tailored based on genomics (read recent review for example), but much more lies ahead, especially in using evidence- based recommendations for use of genomic markers as prognostic and predictive factors.
The long-term implementation and success of cancer genomics in improving cancer care and survival will depend on our ability to track the population impact of new genome-based discoveries in the “real” world and not only in the context of controlled clinical trials. As a deluge of information is generated in the next decade, it will become increasingly crucial to integrate evidence-based genomic information relevant to cancer etiology, response to interventions, and long-term outcomes in cancer surveillance. While much of cancer genomics is still in research mode, several genomic applications are used today in clinical oncology and cancer prevention. The CDC Public Health Genomics Knowledge Base (PHGKB) displays an updated searchable list of genomic tests and applications by their level of evidence based on systematic reviews and guidelines. Tier 1 applications feature tests with highest level of evidence. As of July 27, 2017, PHGKB lists 47 tier 1 genomics applications, most of which (35/47 or 74% are cancer-related).
As the field of cancer genomics matures further, there will be many scientific and logistical challenges to integrate new findings into surveillance and surveillance research. These include, among others, the rapid pace and volume of biomarker discovery and applications; the need for standardized definition of biomarkers; and capture of testing, especially when specimens are sent to reference labs and/or results may not be sent to the settings where cancer registrars collect surveillance data.
In addition to the ongoing challenges of surveillance for cancers related to traditional risk factors such as smoking and obesity, there will be an increasing need for a scientific-based approach to choose relevant genomic applications for cancer surveillance as well as the need to conduct pilot demonstration projects. In addition, the inclusion of these clinically relevant data will require the surveillance community to think in novel ways and work with nontraditional partners such as genomic labs to include these data on a population level. In the long run, cancer genomics, along with other scientific fields such as informatics, geographic analysis, and data linkages, will contribute to a new era of cancer precision surveillance.
As always, we welcome our readers’ input and feedback.
Posted on  by Muin J. Khoury, Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia and Lynne Penberthy, Division of Cancer Control and Population Sciences, National Cancer Institute

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National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer: Journal of Clinical Oncology: Vol 0, No 0

National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer: Journal of Clinical Oncology: Vol 0, No 0



In the United States, 3.8 million women have a history of breast (BC) or ovarian cancer (OC). Up to 15% of cases are attributable to heritable mutations, which, if identified, provide critical knowledge for treatment and preventive care. It is unknown how many patients who are at high risk for these mutations have not been tested and how rates vary by risk criteria.
We used pooled cross-sectional data from three Cancer Control Modules (2005, 2010, 2015) of the National Health Interview Survey, a national in-person household interview survey. Eligible patients were adult females with a history of BC and/or OC meeting select 2017 National Comprehensive Cancer Network eligibility criteria on the basis of age of diagnosis and family history. Outcomes included the proportion of individuals reporting a history of discussing genetic testing with a health professional, being advised to undergo genetic testing, or undergoing genetic testing for BC or OC.
Of 47,218 women, 2.7% had a BC history and 0.4% had an OC history. For BC, 35.6% met one or more select eligibility criteria; of those, 29.0% discussed, 20.2% were advised to undergo, and 15.3% underwent genetic testing. Testing rates for individual eligibility criteria ranged from 6.2% (relative with OC) to 18.2% (diagnosis ≤ 45 years of age). For OC, 15.1% discussed, 13.1% were advised to undergo, and 10.5% underwent testing. Using only four BC eligibility criteria and all patients with OC, an estimated 1.2 to 1.3 million individuals failed to receive testing.
Fewer than one in five individuals with a history of BC or OC meeting select National Cancer Comprehensive Network criteria have undergone genetic testing. Most have never discussed testing with a health care provider. Large national efforts are warranted to address this unmet need.

Oncologist use and perception of large panel next-generation tumor sequencing. - PubMed - NCBI

Oncologist use and perception of large panel next-generation tumor sequencing. - PubMed - NCBI



 2017 Sep 1;28(9):2298-2304. doi: 10.1093/annonc/mdx294.

Oncologist use and perception of large panel next-generation tumor sequencing.

Abstract

BACKGROUND:

Genomic profiling is increasingly incorporated into oncology research and the clinical care of cancer patients. We sought to determine physician perception and use of enterprise-scale clinical sequencing at our center, including whether testing changed management and the reasoning behind this decision-making.

PATIENTS AND METHODS:

All physicians who consented patients to MSK-IMPACT, a next-generation hybridization capture assay, in tumor types where molecular profiling is not routinely performed were asked to complete a questionnaire for each patient. Physician determination of genomic 'actionability' was compared to an expertly curated knowledgebase of somatic variants. Reported management decisions were compared to chart review.

RESULTS:

Responses were received from 146 physicians pertaining to 1932 patients diagnosed with 1 of 49 cancer types. Physicians indicated that sequencing altered management in 21% (331/1593) of patients in need of a treatment change. Among those in whom treatment was not altered, physicians indicated the presence of an actionable alteration in 55% (805/1474), however, only 45% (362/805) of these cases had a genomic variant annotated as actionable by expert curators. Further evaluation of these patients revealed that 66% (291/443) had a variant in a gene associated with biologic but not clinical evidence of actionability or a variant of unknown significance in a gene with at least one known actionable alteration. Of the cases annotated as actionable by experts, physicians identified an actionable alteration in 81% (362/445). In total, 13% (245/1932) of patients were enrolled to a genomically matched trial.

CONCLUSION:

Although physician and expert assessment differed, clinicians demonstrate substantial awareness of the genes associated with potential actionability and report using this knowledge to inform management in one in five patients.

CLINICAL TRIAL NUMBER:

KEYWORDS:

next-generation sequencing; precision medicine; targeted therapy; tumor sequencing

PMID:
 
28911072
 
DOI:
 
10.1093/annonc/mdx294

Long-Term Colorectal Cancer Incidence After Negative Colonoscopy in the State of Utah: The Effect of Family History. - PubMed - NCBI

Long-Term Colorectal Cancer Incidence After Negative Colonoscopy in the State of Utah: The Effect of Family History. - PubMed - NCBI



 2017 Sep;112(9):1439-1447. doi: 10.1038/ajg.2017.193. Epub 2017 Jul 11.

Long-Term Colorectal Cancer Incidence After Negative Colonoscopy in the State of Utah: The Effect of Family History.

Samadder NJ1,2,3Pappas L1Boucherr KM1,4Smith KR1,4,5,6Hanson H1,6,7Fraser A1,6Wan Y1,6Burt RW1,2,8Curtin K1,6,9.

Abstract

OBJECTIVES:

Colonoscopy is widely recommended for colorectal cancer (CRC) screening, but evidence to guide the optimal frequency of repeat screening examination is limited. We examined the duration and magnitude of the risk of developing CRC, following a negative colonoscopy in those at average risk and those with a first-degree family history of CRC.

METHODS:

A cohort of Utah residents aged 50-80 years who had a negative colonoscopy between 1 January 2001 and 31 December 2011 was identified using the Utah Population Database. Patients were followed from the time of the index colonoscopy until diagnosis of CRC, death, migration out of state, repeat colonoscopy, or end of the study period. CRC incidence after the index colonoscopy was compared with that of the state population by standardized incidence ratios (SIRs).

RESULTS:

A cohort of 131,349 individuals at average risk with a negative colonoscopy was identified. Compared with the state population, a negative colonoscopy was associated with SIRs of 0.15 (95% confidence interval (CI): 0.08-0.23) at 1 year, 0.26 (95% CI: 0.19-0.32) at 2-5 years, 0.33 (95% CI: 0.22-0.43) at 5-6 years, and 0.60 (95% CI: 0.44-0.76) at 7-10 years for CRC following the index colonoscopy. In a secondary analysis involving only patients with a first-degree relative with CRC, patients had a significantly lower incidence of CRC only for the first 5 years of follow-up (SIR 0.39, 95% CI: 013-0.64). There was also a difference in the risk of proximal (SIR 0.72, 95% CI: 0.45-0.98) and distal (SIR 0.51, 95% CI: 0.30-0.72) colon cancers at 7-10 years following a negative colonoscopy.

CONCLUSIONS:

The risk of developing CRC remains decreased for at least 10 years following the performance of a negative colonoscopy. However, the lower incidence of CRC in those with a family history of CRC differed in magnitude and timing being limited primarily to the first 5 years of follow-up and of lesser magnitude than that in the overall cohort.

PMID:
 
28695908
 
DOI:
 
10.1038/ajg.2017.193

[Indexed for MEDLINE]

Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer-ready for p... - PubMed - NCBI

Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer-ready for p... - PubMed - NCBI





 2017 Aug;6(4):444-453. doi: 10.21037/tlcr.2017.07.01.

Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer-ready for prime-time?

Pailler E1,2,3Faugeroux V1,2,3Oulhen M1,2Catelain C1,2Farace F1,2,3.

Abstract

In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis. Here we introduce the clinical needs in this disease that mainly consist of the diagnosis of epidermal growth factor receptor (EGFR) activating alterations and anaplastic lymphoma kinase (ALK) rearrangement. We present the proof-of-concept studies that explore the detection of these genetic alterations in CTCs from NSCLC patients. Finally, we discuss steps that are still required before CTCs are routinely used for diagnosis of EGFR-mutations and ALK-rearrangements in this disease.

KEYWORDS:

Circulating tumor cells (CTC); anaplastic lymphoma kinase (ALK) rearrangement; epidermal growth factor receptor (EGFR) mutations; non-small cell lung cancer (NSCLC)

PMID:
 
28904888
 
PMCID:
 
PMC5583075
 
DOI:
 
10.21037/tlcr.2017.07.01

MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer - A systematic review and meta-analysis. - PubMed - NCBI

MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer - A systematic review and meta-analysis. - PubMed - NCBI



 2017 Sep;214(3):515-524. doi: 10.1016/j.amjsurg.2017.03.049. Epub 2017 Apr 26.

MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer - A systematic review and meta-analysis.

Abstract

OBJECTIVES:

The aim of this systematic review and meta-analysis is to summarize the current knowledge regarding microRNA-21 and to evaluate its prognostic impact in patients with pancreatic cancer.

METHODS:

We conducted an electronic literature search to identify all published studies in PubMed/MEDLINE, Scopus and Google Scholar databases from 2000 until August 2016.

RESULTS:

A total of 17 studies involving 1471 patients met the inclusion criteria for the quantitative synthesis. The microRNA-21 upregulation was significantly associated with poorer overall survival, disease-free survival, and progression-free survival. The subgroup analysis revealed that microRNA-21 overexpression has a significant higher prognostic value for patients who receive adjuvant chemotherapy. Increased microRNA-21 was associated with a statistically significant higher rate of metastatic lymph nodes and poorly differentiated tumors.

CONCLUSIONS:

MicroRNA-21 upregulation in pancreatic cancer is associated with a significantly poorer overall survival, disease-free survival, and progression-free survival. MicroRNA-21 may be a useful prognostic biomarker, allowing stratification for chemotherapy administration, and being a component of precision medicine in patients with pancreatic cancer.

KEYWORDS:

Meta-analysis; MicroRNA-21; Pancreatic cancer; Prognosis

PMID:
 
28477839
 
DOI:
 
10.1016/j.amjsurg.2017.03.049

[Indexed for MEDLINE]