OVARIAN CANCER and US: genetic testing

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Showing posts with label genetic testing. Show all posts
Showing posts with label genetic testing. Show all posts

Wednesday, July 11, 2012

paywalled: Preferences for outcomes associated with decisions to undergo or forego genetic testing for Lynch syndrome



Preferences for outcomes associated with decisions to undergo or forego genetic testing for Lynch syndrome

Abstract

BACKGROUND:

Current guidelines recommend offering genetic testing for Lynch syndrome to individuals whose tumors suggest this condition and to relatives of affected individuals. Little is known, however, regarding how patients view the prospect of such testing. In addition, data on preferences (utilities) for the potential outcomes of testing decisions for use in cost-effectiveness analyses are lacking.

METHODS:

Time tradeoff utilities were elicited for 10 potential outcomes of Lynch syndrome testing decisions and 3 associated cancers from 70 participants, representing a range of knowledge about and experiences with Lynch syndrome.

RESULTS:

Highest mean utilities were assigned to scenarios in which only the assessor's sibling had Lynch-associated colorectal cancer (ranging from 0.669 ± 0.231 to 0.760 ± 0.220). Utilities assigned to scenarios in which the assessor had Lynch-associated colorectal cancer ranged from 0.605 ± 0.252 to 0.682 ± 0.246, whereas the lowest mean utilities were assigned to 2 of the general cancer states (0.601 ± 0.238 and 0.593 ± 0.272 for colorectal and ovarian cancer respectively). Only 43% of the sample assigned higher values to undergoing Lynch testing and receiving negative results versus foregoing Lynch testing, whereas 50% assigned higher values to undergoing rather than foregoing surgery to prevent a subsequent cancer.

CONCLUSIONS:

Genetic testing for Lynch syndrome, regardless of results, can have profound effects on quality of life; the utilities we collected can be used to incorporate these effects into cost-effectiveness analyses. Importantly, preferences for the potential outcomes of testing vary substantially, calling into question the extent to which patients would avail themselves of such testing if it were offered to them. Cancer 2012. © 2012 American Cancer Society


Monday, June 18, 2012

Predisposed to risk but not change CMAJ (genetic testing series)




......Of course, considering that the predictive power of genetic testing tends to be underwhelming, perhaps it’s no surprise that personalized genetic information induces more shoulder shrugs than lifestyle changes. “One of the challenges is that people are behaving rationally, to a degree, when they don’t change their behaviours. These genetic tests aren’t very predictive,” says Timothy Caulfield, a Canada Research Chair in Health Law and Technology who teaches in the law faculty and school of public health at the University of Alberta. “If you find you have a health risk of 2% instead of 1%, that type of risk is lost in the noise of risk in your life.” 

Editor’s note: Sixth of a multipart series on genetic testing.


Part 1: Separating hype from reality in the era of the affordable genome (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4143).
Part 2: Popping the genetics bubble (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4142).
Part 3: Who should hold the keys to your DNA? (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4141).
Part 4: A race-based detour to personalized medicine (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4133).
Part 5: Race and genetics in the doctor’s office (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4134).

Saturday, May 26, 2012

PLoS ONE: The KRAS-Variant Is Associated with Risk of Developing Double Primary Breast and Ovarian Cancer (study of pts with both ovarian and breast cancers)



Blogger's Note: the other cancers (KRAS mutations) referred to beyond ovarian and breast cancers include references to lung and melanoma cancers; KRAS mutations have been established in colorectal cancers, however, there are no references on this particular subject within this research article regarding Lynch Syndrome -
an ongoing area of specific research (re: KRAS/Lynch Syndrome/blog posting of May 16, 2012 Jnl ASCP)
                                      ~~~~~~~~~~~~~~~~~~~
PLoS ONE: The KRAS-Variant Is Associated with Risk of Developing Double Primary Breast and Ovarian Cancer


Table 1. The KRAS-variant is significantly associated with uninformative breast and ovarian cancer patients.
doi:10.1371/journal.pone.0037891.t001

Purpose

A germline microRNA binding site-disrupting variant, the KRAS-variant (rs61764370), is associated with an increased risk of developing several cancers. Because this variant is most strongly associated with ovarian cancer risk in patients from hereditary breast and ovarian families (HBOC), and with the risk of premenopausal triple negative breast cancer, we evaluated the association of the KRAS-variant with women with personal histories of both breast and ovarian cancer, referred to as double primary patients.

Conclusions

These findings further validate the importance of the KRAS-variant in breast and ovarian cancer risk, and support the association of this variant as a genetic marker for HBOC families previously considered uninformative.


Introduction 

Hereditary breast and ovarian cancer (HBOC) syndrome is an inherited cancer-susceptibility syndrome marked by an increased risk of developing both ovarian cancer and breast cancer [1]. Families generally considered as having HBOC syndrome are those with multiple family members that have one of these cancers, especially at young ages, or an individual with a cancer in both organs, a “double primary” patient. While this is a relatively rare presentation, a substantial number of women develop both breast and ovarian primaries over their lifetime. While BRCA1 and BRCA2 are strongly associated with HBOC syndrome [2], a large number of HBOC families and women with double primary cancer do not have detectable genetic mutations (herein referred to as “uninformative” patients).
The chances of identifying a mutation causative for HBOC increase when testing individuals diagnosed with double breast/ovarian primaries [3][5]. However, a recent report suggests that the rates of BRCA mutations are not higher in a patient with a double primary without a family history than that for isolated first degree relative pairs with single primaries (14% versus 17% with mutations, respectively) [4]. This supports the importance of family history even in patients with double primary cancers. Although BRCA mutations were found in 49% of double primary patients in this recent analysis, it should be noted that this indicates that over half of double primary patients do not have a known genetic cause for their disease. This is consistent with other reports of these patients [3], [5].............The goal of this study was to determine the association of the KRAS-variant with women with double primary breast and ovarian cancer, to further validate the association of this variant with HBOC families. Findings here support the importance of the KRAS-variant in uninformative HBOC families as well as in predicting the risk of multiple primary cancers in women.......

Association of the KRAS-variant with Multiple Cancers in All Patients

Because the KRAS-variant has been found to be associated with an increased risk for other cancers besides breast and ovarian cancer [11], [15] we tested the hypothesis that the KRAS-variant would predict for an increased risk of developing additional cancers in this double primary cohort, regardless of BRCA mutation status. For 183 of the patients in our study where this information was available, 79.2% (n = 145) had reported just the two cancers (breast and ovarian), 12.0% (n = 22) had two separate primary breast cancers and also ovarian cancer, and 8.7% (n = 16) had cancer in an additional organ outside of the breast and ovary (triple primary).

Wednesday, May 09, 2012

paywalled: The Predictive Capacity of Personal Genome Sequencing - Science Translational Medicine



[Research Articles] The Predictive Capacity of Personal Genome Sequencing:

New DNA sequencing methods will soon make it possible to identify all germline variants in any individual at a reasonable cost. However, the ability of whole-genome sequencing to predict predisposition to common diseases in the general population is unknown. To estimate this predictive capacity, we use the concept of a "genometype." A specific genometype represents the genomes in the population conferring a specific level of genetic risk for a specified disease. Using this concept, we estimated the maximum capacity of whole-genome sequencing to identify individuals at clinically significant risk for 24 different diseases.

Saturday, May 05, 2012

paywalled: Prophylactic oophorectomy rates in relation to a guideline update on referral to genetic counseling



Prophylactic oophorectomy rates in relation to a guideline update on referral to genetic counseling: Publication year: 2012


Source: Gynecologic Oncology

Objective We sought to determine whether prophylactic oophorectomy rates changed after the introduction of a 2007 health plan clinical guideline recommending systematic referral to a genetic counselor for women with a personal or family history suggestive of an inherited susceptibility to breast/ovarian cancer.

Methods We conducted a retrospective cohort study of female members of Group Health, an integrated delivery system in Washington State. Subjects were women aged ≥35years during 2004–2009 who reported a personal or family history consistent with an inherited susceptibility to breast/ovarian cancer. Personal and family history information was collected on a questionnaire completed when the women had a mammogram. We ascertained oophorectomies from automated claims data and determined whether surgeries were prophylactic by medical chart review.....

Results Prophylactic oophorectomy rates were relatively unchanged after compared to before the guideline change, 1.0 versus 0.8/1,000 person-years, (IRR=1.2; 95% CI: 0.7-2.0), whereas bilateral oophorectomy rates for other indications decreased. Genetic counseling receipt rates doubled after the guideline change (95% CI: 1.7-2.4) from 5.1 to 10.2/1,000 person-years. During the study, bilateral oophorectomy rates were appreciably greater in women who saw a genetic counselor compared to those who did not regardless of whether they received genetic testing as part of their counseling.

Conclusion A doubling in genetic counseling receipt rates lends support to the idea that the guideline issuance contributed to sustained rates of prophylactic oophorectomies in more recent years.

Tuesday, April 24, 2012

open access: Viewpoint: Quality standards and samples in genetic testing - Journal of Clinical Pathology



Blogger's Note: includes reference to BRCA/

Quality standards and samples in genetic testing -- Ravine and Suthers 65 (5): 389 -- Journal of Clinical Pathology

Conclusion

The goal of a clinician is to provide the patient with an accurate diagnosis, prognosis and therapeutic options, including in relation to diseases for which genetic tests are available. Similarly, the goal of a medical laboratory is to provide the right result for the right patient in a timely fashion every time. Alexander Pope wrote in An Essay on Criticism that ‘To err is human…’. Three hundred years later, his message is still potent. All arenas of human endeavour are at risk of human error, and the emerging discipline of genetic testing is not immune. Errors will occur here, as they do in other areas of laboratory testing, and medicine in general. It is of little comfort that sample errors, such as WBIT, are likely to be more common than reports of adverse incidents. 

Like the proverbial elephant in the room, we know the errors are present but we hesitate to talk about them. The issue must be addressed, however, because errors in genetic testing have the potential to prompt clinical decisions with a high risk of attendant harm. They may also direct important life choices for those being tested, with ramifications that may influence human health and welfare at all developmental stages. Some errors will invariably lead to outcomes over which the person being tested will have no control, such as wrongful conviction in a court of law. Errors in genetic testing may also waste the increasingly scarce health dollars, and place individual healthcare practitioners at professional, legal and financial risk. It is now time for the profession to consider the full range of errors that are possible along the genetic test processing chain from patient to result, and devise appropriate risk minimisation strategies. Until such data are available, individual healthcare practitioners involved in genetic testing should consider the associated possible risks to patient health and welfare, and look beyond the baseline standard of testing a single sample.

Thursday, April 12, 2012

CMAJ: Young women with breast cancer genes face tough choices (8th part of a series in genetic testing - see links)



CMAJ: Young women with breast cancer genes face tough choices

Editor’s note: Eighth of a multipart series on genetic testing.


Part 1: Separating hype from reality in the era of the affordable genome (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4143).
Part 2: Popping the genetics bubble (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4142).
Part 3: Who should hold the keys to your DNA? (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4141).
Part 4: A race-based detour to personalized medicine (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4133).
Part 5: Race and genetics in the doctor’s office (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4134).
Part 6: Predisposed to risk but not change (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4157).
Part 7: Unhealthy behaviours influenced by genes and environment (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4162).

open access: A Pilot study of the Sharing Risk Information Tool (ShaRIT) for Families with Hereditary Breast and Ovarian Cancer Syndrome - study of 19 BRCA carriers





A Pilot study of the Sharing Risk Information Tool (ShaRIT) for Families with Hereditary Breast and Ovarian Cancer Syndrome 

 ".....ShaRIT strives to ease the “burden of the messenger” and decrease the possibility of mis-communicating and misinterpreting
important medical information to their relatives."

Tuesday, April 10, 2012

abstract: Medium-sized deletion in the BRCA1 gene: Limitations of Sanger sequencing and MLPA analyses.



Medium-sized deletion in the BRCA1 gene: Limitations of Sanger sequencing and MLPA analyses

Sanger sequencing and MLPA analyses.
Genet Mol Biol. 2012

Abstract
We describe a family with a history of breast and ovarian cancer in which MLPA analysis of the BRCA1 gene pointed to a deletion including a part of exon 11. Further characterization confirmed a loss of 374 bp in a region completely covered by conventional sequencing which had not revealed the deletion. Because this alteration was only detected serendipitously with an MLPA probe, we calculated the probabilities of detecting medium-sized deletions in large exons by methods including initial PCR amplification. This showed that a considerable fraction of medium-sized deletions are undetectable by currently used standard methods of mutation analyses. We conclude that long, widely overlapping amplicons should be used to minimize the risk of missing medium-sized deletions. Alternatively, large exons could be completely covered by narrow-spaced MLPA probes.



abstract: BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : small study 14 Ashkenazi Jewish women



BRCA genetic testing of individuals from families with low prevalence of cancer: experiences of carriers and implications for population screening : Genetics in Medicine : Nature Publishing Group

Purpose:

BRCA genes are associated with hereditary breast and ovarian cancers. Guidelines worldwide currently recommend BRCA genetic testing in asymptomatic individuals only if they belong to “high-risk” families. However, population screening for BRCA1/2 may be the logical next step in populations with a high prevalence of founder mutations, such as Ashkenazi Jews. This study aimed to explore (i) the impact of a positive BRCA genetic test result on individuals who have neither a personal history nor a familial history of cancer and (ii) their attitudes toward the concept of population screening.

Methods:

Semistructured in-depth interviews were carried out with 14 Ashkenazi Jewish women who were asymptomatic BRCA carriers and who belonged to families with low prevalence of cancer.

Results:

Three main findings emerged: (i) having no family history of cancer was a source of optimism but also confusion; (ii) engaging in intensified medical surveillance and undergoing preventive procedures was perceived as health-promoting but also tended to induce a sense of physical and psychological vulnerability; and (iii) there was overall support for BRCA population screening, with some reservations.

Conclusion:

Women belonging to low-cancer-prevalence families within a “high-risk” ethnic community view BRCA genetic testing positively despite the difficulties entailed, because it allows prevention or early detection of cancer. However, implementing a BRCA population screening program should be carried out with proper pre- and post-testing preparation and support for the individuals undergoing testing.

Thursday, April 05, 2012

abstract: Eligibility criteria in private and public coverage policies for BRCA genetic testing and genetic counseling.



Eligibility criteria in private and public coverage policies for BRCA genetic testing and genetic counseling

Genet Med. 2011 Dec;13(12):1045-50. doi: 10.1097/GIM.0b013e31822a8113.

Abstract

PURPOSE:

Coverage policies for genetic services for hereditary cancers are of interest because the services influence cancer risk reduction for both persons with cancer and their family members. We compared coverage policies for BRCA genetic testing and genetic counseling among selected payers in the United States to illuminate eligibility criteria variation that may explain differential access by insurance type. We compared these policies with policies for breast cancer screening with magnetic resonance imaging to consider whether payers apply a unique policy approach to genetic services.

METHODS:

We conducted a case study of large private and public payers selected on number of covered lives. We examined coverage policies for BRCA genetic testing, genetic counseling, and screening with magnetic resonance imaging and the eligibility criteria for each. We compared eligibility criteria against National Comprehensive Cancer Network guidelines.

RESULTS:

Eligibility criteria for BRCA testing were related to personal history and family history of cancer. Although private payers covered BRCA testing for persons with and without cancer, the local Medicare carrier in our study only covered testing for persons with cancer. In contrast, Arizona's Medicaid program did not cover BRCA testing. Few payers had detailed eligibility criteria for genetic counseling. Private payers have more detailed coverage policies for both genetic services and screening with magnetic resonance imaging in comparison with public payers.

CONCLUSION:

Despite clinical guidelines establishing standards for BRCA testing, we found differences in coverage policies particularly between private and public payers. Future research and policy discussions can consider how differences in private and public payer policies influence access to genetic technologies and health outcomes.

Monday, April 02, 2012

Gene Maps Are No Cure-All - WSJ.com (references ovarian cancer as an example)



Gene Maps Are No Cure-All - WSJ.com

"The new study, published Monday in the journal Science Translational Medicine and presented at a meeting of the American Association for Cancer Research in Chicago, was based on data from thousands of twins in five countries. It found that for 23 of 24 diseases analyzed, most patients would get negative test results, suggesting that their risk of being stricken with these diseases is low.
In reality, the study says, their risk would be only slightly lower than that of the general population. Patients who have been gene-sequenced, particularly without a doctor's counsel, could be lulled into a false sense of security.....

"For example, one of the diseases studied was ovarian cancer. Dr. Vogelstein noted that of the 156 million or so women in the U.S., about 2.2 million are expected to get ovarian cancer at some point. But even if every woman got a whole-genome scan, the tests would be able to identify only 100,000 of them, Dr. Vogelstein said. "That tells you that 2.1 million women cannot be alerted to the fact that they will get the cancer," he said......

Monday, March 12, 2012

Blogger: “And you’re ugly too” | genomeboy (genetic testing/patents, brca....)



“And you’re ugly too” | genomeboy

"All of this, of course, was precipitated by AMP v. USPTO (“The Myriad Case”), in which patients with family histories of breast cancer asserted that they have not been able to get confirmatory or “second opinion” testing because there is but a single, exclusive licensee of the patents on the most clinically important genes that predispose to hereditary breast and ovarian cancer, BRCA1 and BRCA2.

I attended the public hearing at the USPTO in Alexandria, VA on 16 February 2012.  I was so appalled by what I heard that I attended the second one in San Diego on 9 March 2012 and testified. I am still adding links to my testimony in order to submit it before public comment closes on 26 March 2012. Here is a brief excerpt on Myriad’s unwillingness to share its mutation data:................"

CMAJ: Who should hold the keys to your DNA?




Editor’s note: Third of a multipart series on genetic testing.
Part 1: Separating hype from reality in the era of the affordable genome (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4143).
Part 2: Popping the genetics bubble (www.cmaj.ca/lookup/doi/10.1503/cmaj.109-4142).
Next: Race and genetics in the doctor’s office



CMAJ: Who should hold the keys to your DNA?

"Opinion is divided over whether doctors or patients should be receiving the results of direct-to-consumer genetic tests........."

"“I think there is a need to think this through and to have some balance. On the one hand, we should respect consumers’ preferences and freedom to choose,” says Peter Neumann, director of the Center for the Evaluation of Value and Risk in Health at the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center in Boston, Massachusetts and lead author on the paper. “We should also inform them about the risks and benefits.”
In some countries, governments have stepped in to ensure that doctors are the ones who must inform consumers about risks and benefits. Laws in France, Germany, Portugal and Switzerland stipulate that genetic tests only be administered by physicians. There are no regulations in Canada and few in the United States, though the US Food and Drug Administration has indicated that it will be stepping up efforts in the area...." 

Saturday, March 10, 2012

open access: The use of telephone in genetic counseling versus in-person counseling: a randomized study on counselees’ outcome



"In total only 15% of the referred participants declined
participation in the questionnaire study, indicating a highly
motivated population. Non-participants were equally distributed
between telephone and in-person OGNC, speaking
in favor of an unbiased cohort."

"Given the results of our study, the option of a pre-counseling
telephone model could be an equal or even better
alternative to in-person counseling and could very well be a
standard mode in the future. The results show that a considerable
number of participants experienced difficulties
with the process of creating a pedigree and dissatisfaction
with information on recommended surveillance and prevention.
These items should be areas of improvement."

Monday, February 13, 2012

open access: Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist’s initiative



Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist’s initiative

"....One limitation of our study was the low response rate in the eligible patients. This may have biased our results, especially if the surgeons had consciously avoided recruiting patients with a (very) poor prognosis or emotional problems. Such bias would have resulted in underestimation of psychological distress. At present, we cannot assess whether bias was present. However, we note that in our sample, the levels of psychological distress were lower than those described in the literature. 

Another reason for the low response rate may have been the complex logistic inclusion procedure [15], if communication of the test result to the patient exceeded the inclusion criterion of 6 months. In some cases, it took several months before the MSI-test report, written by the pathologist, was sent to the surgeon and a number of weeks more before the patient was contacted. Another limitation of our study was that no firm conclusions could be drawn, because the large number of tests increased the possibility of a type I error, which we have not corrected for. 

Despite some methodological concerns, we can conclude that moderate levels of distress were present following MSI testing in patients recently diagnosed with CRC. These levels were similar to those in other patients diagnosed with CRC [27, 47, 48]. 

High cancer-specific distress was observed in 40% of the MSI-positive patients and was significantly correlated with female gender."