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

UC DavisWednesday, July 26, 2017

Credit: Susan Merrell/UCSF

Laura Esserman, professor of surgery and director of the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center, is leading the new Women Informed to Screen Depending on Measures of Risk (WISDOM) study.

Sorting out when or whether to get mammograms can be perplexing for any woman, and a health provider’s advice may not settle the matter. That’s because even experts disagree about when screening mammography is appropriate and for whom.

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

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Abstract

The pathogenesis of breast cancer, the most frequent female malignancy, entails both genetic and acquired risk factors. Among the various oncogenetic mutations, those involving the BReast Cancer 1 (BRCA1) and BReast Cancer 2 (BRCA2) genes are associated with an extremely high risk of developing breast cancer, with a penetration approximating 70% in women with a positive family history for this malignancy. This important evidence elicits some pragmatic considerations, such as the clinical effectiveness of screening for the most penetrant BRCA mutations in women with or without a positive familial history, but also raises important issues related to the most appropriate clinical management of these patients. Despite it seems now almost certain that BRCA testing should be offered to women with a positive familial history for breast cancer, the balance between advantages and limitations of a population screening remains largely debated. Whatever conclusion can be reach at this point in time must be accurately weighed against at least four different perspectives, which include the low prevalence of these mutations in the general population, the relatively lower risk of developing breast cancer in women without a familial history for this malignancy, the direct and indirect cost of genetic testing and, last but not least, the many potential psychological and clinical consequences in patients receiving a positive test result. Many of these still unresolved issues will be tentatively discussed in this article.

Keywords: Breast cancer, BRCA, BReast Cancer 1 (BRCA1), BReast Cancer 2 (BRCA2

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

Giuseppe Lippi,¹ Camilla Mattiuzzi,² and Martina Montagnana¹

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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

By The ASCO Post
Posted: 8/4/2017 10:20:31 AM
Last Updated: 8/4/2017 10:20:31 AM
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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

JAMA Oncol. 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.

Ruijs MWG1, Loo CE2, van Buchem CAJM2, Bleiker EMA3, Sonke GS4.

Author information

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

J Genet Couns. 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.

Liang MI1,2, Wong DH1, Walsh CS2, Farias-Eisner R1, Cohen JG3.

Author information

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

Cancer. 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.

Nguyen KA1, Syed JS1, Espenschied CR2, LaDuca H2, Bhagat AM1, Suarez-Sarmiento A1, O'Rourke TK Jr3, Brierley KL4, Hofstatter EW5, Shuch B1,6.

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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.

© 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

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

Telomeres and telomerase in prostate cancer development and therapy.

Graham MK1, Meeker A1.

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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