Amanda Gammon - Academia.edu (original) (raw)

Papers by Amanda Gammon

The Hereditary Basis of Childhood Cancer

JCO Precision Oncology

PURPOSE To compare the classification of genetic variants reported on tumor genomic profiling (TG... more PURPOSE To compare the classification of genetic variants reported on tumor genomic profiling (TGP) reports with germline classifications on clinical test results and ClinVar. Results will help to inform germline testing discussions and decisions in patients with tumor variants in genes that are relevant to hereditary cancer risk. PATIENTS AND METHODS This study compared somatic and germline classifications of small nucleotide variants in the following genes: BRCA1, BRCA2, CHEK2, PALB2, ATM, MLH1, MSH2, MSH6, and PMS2. Somatic classifications were taken from reports from a single commercial TGP laboratory of tests ordered by providers at Huntsman Cancer Institute between March 2014 and June 2018. Somatic variant interpretations were compared with classifications from germline test results as well as with ClinVar interpretations. RESULTS Of the 623 variants identified on TGP, 353 had a definitive classification in ClinVar, and 103 were assayed with a germline test, with 66 of the var...

Journal of Genetic Counseling

American Journal of Gastroenterology

Cancer Medicine

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

ABSTRACTBackground and AimsGenes associated with hereditary breast and ovarian cancer (HBOC) and ... more ABSTRACTBackground and AimsGenes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) susceptibility have been shown to play a role in pancreatic cancer susceptibility. Germline genetic testing of pancreatic cancer cases could be beneficial for at-risk relatives with pathogenic variants in established HBOC and CRC genes, but it is unclear what proportion of pancreatic cancer cases harbor pathogenic variants in these genes.Methods66 pancreatic cancer cases, unselected for family history and diagnosed at the Huntsman Cancer Hospital (HCH), were sequenced on a custom 34-gene panel including known HBOC and CRC genes. A second set of 156 unselected HCH pancreatic cancer cases were sequenced on an expanded 59-gene panel (n=95) or with a custom 14-gene clinical panel (n=61). Sequencing data from both sets of pancreatic cancer cases, the pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unselected pancreatic cancer screen from the Mayo Clin...

BMC cancer, Jan 27, 2018

Genes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) pre... more Genes associated with hereditary breast and ovarian cancer (HBOC) and colorectal cancer (CRC) predisposition have been shown to play a role in pancreatic cancer susceptibility. Growing evidence suggests that pancreatic cancer may be useful as a sentinel cancer to identify families that could benefit from HBOC or CRC surveillance, but to date pancreatic cancer is only considered an indication for genetic testing in the context of additional family history. Preliminary data generated at the Huntsman Cancer Hospital (HCH) included variants identified on a custom 34-gene panel or 59-gene panel including both known HBOC and CRC genes for respective sets of 66 and 147 pancreatic cancer cases, unselected for family history. Given the strength of preliminary data and corresponding literature, 61 sequential pancreatic cancer cases underwent a custom 14-gene clinical panel. Sequencing data from HCH pancreatic cancer cases, pancreatic cancer cases of the Cancer Genome Atlas (TCGA), and an unse...

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jan 29, 2017

This study evaluates predictors of BRCA1/2 testing among breast and ovarian cancer survivors who ... more This study evaluates predictors of BRCA1/2 testing among breast and ovarian cancer survivors who received genetic counseling as part of a randomized trial and evaluates moderators of counseling mode on testing uptake. Predictors of BRCA1/2 testing within 1-year post-counseling were evaluated using multivariable logistic regression in a population-based sample of breast and ovarian cancer survivors at increased hereditary risk randomly assigned to in-person (IPC; n = 379) vs. telephone counseling (TC; n = 402). Variables that moderated the association between counseling mode and testing were identified by subgroup analysis. Testing uptake was associated with higher perceived comparative mutation risk (OR = 1.32, 95% CI = 1.11, 1.57) in the adjusted analysis. Those without cost barriers had higher testing uptake (OR = 18.73, 95% CI = 7.09, 49.46). Psychological distress and perceived comparative mutation risk moderated the effect of counseling and testing. Uptake between IPC vs. TC di...

Cancer, Jan 13, 2017

As panel testing becomes more common in clinical practice, it is important to understand the prev... more As panel testing becomes more common in clinical practice, it is important to understand the prevalence and trends associated with the pathogenic variants (PVs) identified. This is especially true for genetically heterogeneous cancers, such as breast cancer (BC), in which PVs in different genes may be associated with various risks and cancer subtypes. The authors evaluated the outcomes of genetic testing among women who had a personal history of BC. A total of 35,409 women with a single diagnosis of BC who underwent clinical genetic testing with a 25-gene panel were included in the current analysis. Women with multiple BCs and men with BC were excluded. The frequency and distribution of PVs were assessed for the overall cohort, among women with triple-negative BC (TNBC) (n = 4797), and by age at diagnosis. PVs were identified in 9.3% of women tested; 51.5% of PVs were identified in genes other than breast cancer 1 (BRCA1) and BRCA2, including checkpoint kinase 2 (CHEK2) (11.7%), ata...

Journal of Genetic Counseling, 2016

Scientific advances have allowed the development of multiplex gene-panels to assess many genes si... more Scientific advances have allowed the development of multiplex gene-panels to assess many genes simultaneously in women who have tested negative for BRCA1/2. We examined correlates of interest in testing for genes that confer modest and moderate breast cancer risk and risk communication preferences for women from BRCA negative families. Female first-degree relatives of breast cancer patients who tested negative for BRCA1/2 mutations (N = 149) completed a survey assessing multiplex genetic testing interest and risk communication preferences. Interest in testing was high (70 %) and even higher if results could guide risk-reducing behavior changes such as taking medications (79 %). Participants preferred to receive genomic risk communications from a variety of sources including: primary care physicians (83 %), genetic counselors (78 %), printed materials (71 %) and the web (60 %). Factors that were independently associated with testing interest were: perceived lifetime risk of developing cancer (odds ratio (OR) = 1.67: 95 % confidence interval (CI) 1.06-2.65) and high cancer worry (OR = 3.12: CI 1.28-7.60). Findings suggest that women from BRCA1/2 negative families are a unique population and may be primed for behavior change. Findings also provide guidance for clinicians who can help develop genomic risk communications, promote informed decision making and customize behavioral interventions.

The Journal for Nurse Practitioners, 2016

One size does not fit all for breast cancer screening. Early detection and prevention are most ef... more One size does not fit all for breast cancer screening. Early detection and prevention are most effective for those most at risk. Several United States organizations recommend offering annual screening breast magnetic resonance imaging in addition to mammography for women with > 20% lifetime risk for breast cancer using models that take extensive family history into account. The purpose of this article is to help nurse practitioners make critical decisions about breast cancer screening and referrals to genetic services for women based on their lifetime risk for breast cancer. This article reviews several software-based risk assessment models and provides instructions for using the Tyrer-Cuzick model.

The Application of Clinical Genetics, 2016

Cowden syndrome (CS) is an often difficult to recognize hereditary cancer predisposition syndrome... more Cowden syndrome (CS) is an often difficult to recognize hereditary cancer predisposition syndrome caused by mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN). In addition to conferring increased cancer risks, CS also predisposes individuals to developing hamartomatous growths in many areas of the body. Due to the rarity of CS, estimates vary on the penetrance of certain phenotypic features, such as macrocephaly and skin findings (trichilemmomas, mucocutaneous papules), as well as the conferred lifetime cancer risks. To address this variability, separate clinical diagnostic criteria and PTEN testing guidelines have been created to assist clinicians in the diagnosis of CS. As knowledge of CS increases, making larger studies of affected patients possible, these criteria continue to be refined. Similarly, the management guidelines for cancer screening and risk reduction in patients with CS continue to be updated. This review will summarize the current literature on CS to assist clinicians in staying abreast of recent advances in CS knowledge, diagnostic approaches, and management.

Journal of oncology practice / American Society of Clinical Oncology, 2016

Many individuals at risk for BRCA1 or BRCA2 mutations do not have access to trained genetic couns... more Many individuals at risk for BRCA1 or BRCA2 mutations do not have access to trained genetic counselors. This study conducted an economic evaluation alongside a clinical trial of approaches to extending the reach of genetic testing services to geographically underserved populations. Telephone genetic counseling was less expensive than in-person services delivered in the community per individual counseled, individual tested, or mutation detected. For example, it cost an average of 120(range,120 (range, 120(range,80 to 200)perpersoncounseledinthetelephonecounselingarmcomparedwith200) per person counseled in the telephone counseling arm compared with 200)perpersoncounseledinthetelephonecounselingarmcomparedwith270 (range, 180to180 to 180to400) for in-person counseling. One-way sensitivity analyses showed that the average cost per participant remained consistently lower in the telephone counseling arm than in the in-person counseling arm across the range values for each cost parameter and for each study outcome. Microcosting was used to enumerate resources for counseling delivered at 14 primary care clinics (nine geographically re...

Surgical Oncology Clinics of North America, 2015

In the past decade, laws have been passed to provide legal protections against genetic discrimina... more In the past decade, laws have been passed to provide legal protections against genetic discrimination. Many members of the public and medical providers are unaware of the legislation, and concerns about genetic privacy can prevent delivery of optimal medical care. Patient health information, including genetic testing and family history, is protected under the Health Insurance Portability and Accountability Act and the Genetic Information Nondiscrimination Act. Additional protections are granted through the Americans with Disabilities Act, state laws, and the Affordable Care Act. Communicating a genetic test result back to a patient is important for medical management decisions and family members.

Journal of the National Cancer Institute, 2014

The growing demand for cancer genetic services underscores the need to consider approaches that e... more The growing demand for cancer genetic services underscores the need to consider approaches that enhance access and efficiency of genetic counseling. Telephone delivery of cancer genetic services may improve access to these services for individuals experiencing geographic (rural areas) and structural (travel time, transportation, childcare) barriers to access. This cluster-randomized clinical trial used population-based sampling of women at risk for BRCA1/2 mutations to compare telephone and in-person counseling for: 1) equivalency of testing uptake and 2) noninferiority of changes in psychosocial measures. Women 25 to 74 years of age with personal or family histories of breast or ovarian cancer and who were able to travel to one of 14 outreach clinics were invited to participate. Randomization was by family. Assessments were conducted at baseline one week after pretest and post-test counseling and at six months. Of the 988 women randomly assigned, 901 completed a follow-up assessmen...

Journal of Genetic Counseling, 2011

This study was an investigation of awareness, cognitions, and psychosocial and educational needs ... more This study was an investigation of awareness, cognitions, and psychosocial and educational needs related to genetic counseling and testing among Latinas and non-Latina whites at increased risk for having a BRCA1/2 mutation. Sixty-three Latina and eighty-four non-Latina white women completed telephone surveys employing a mixture of quantitative and qualitative questions assessing awareness, benefits, risks, barriers, and genetic counseling communication preferences regarding BRCA1/2 testing. Among participants who had not previously had genetic counseling/testing, 56.9% of Latinas (29/51) and 34.8% of non-Latina white participants (24/69) were unaware of the availability of BRCA1/2 testing. In multivariate logistic regression analysis, Latina ethnicity was the only statistically significant independent factor associated with lack of awareness (OR = 0.42; 95% CI = 0.19-0.35). No appreciable differences were noted between ethnic groups regarding perceived benefits of BRCA1/2 testing or desired genetic counseling topics. These findings underscore the importance of increasing awareness of cancer genetic counseling and genetic testing among both Latina and non-Latina white populations.

Journal of Clinical Oncology, 2014

Purpose Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genet... more Purpose Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery. Patients and Methods Participants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC participants received in-person pre- and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC. Results TC was noninferior to UC on all primary outcomes. At 2 w...

Human Mutation, 2012

Unclassified sequence variants (UV) arising from clinical mutation screening of cancer susceptibi... more Unclassified sequence variants (UV) arising from clinical mutation screening of cancer susceptibility genes present a frustrating issue to clinical genetics services and the patients that they serve. We created an open-access database holding missense substitutions from the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2. The main inclusion criterion is that each variant should have been assessed in a published work that used the Bayesian integrated evaluation of unclassified BRCA gene variants. Transfer of data on these substitutions from the original publications to our database afforded an opportunity to analyze the missense substitutions under a single model and to remove inconsistencies that arose during the evolution of the integrated evaluation over the last decade. This analysis also afforded the opportunity to reclassify these missense substitutions according to the recently published IARC 5-Class system. From an initial set of 248 missense substitutions, 31 were set aside due to non-negligible probability to interfere with splicing. Of the remaining substitutions, 28 fell into one of the two pathogenic classes (IARC Classes 4 or 5), 174 fell into one of the two non-pathogenic classes (IARC Classes 1 or 2), and 15 remain in IARC Class 3, "Uncertain". The database is available at <http://brca.iarc.fr/LOVD>.

Genetics in Medicine, 2010

Purpose: To inform development of a culturally sensitive hereditary breast and ovarian cancer com... more Purpose: To inform development of a culturally sensitive hereditary breast and ovarian cancer communication initiative and related clinical genetic services. Methods: Five focus groups were conducted with 51 female and male Latinos. Educational materials were designed to communicate information about hereditary breast or ovarian cancer and availability of relevant clinical services or prevention strategies. Focus groups explored participants' knowledge, attitudes, and beliefs about hereditary breast and ovarian cancer, BRCA1/2 testing, and communication preferences for hereditary breast and ovarian cancer health messages. Results: Overall, awareness of familial breast and ovarian cancer and availability of genetic risk assessment was low. Once informed, participants held favorable attitudes toward risk assessment and counseling services. Critical themes of the research highlighted the need to provide bilingual media products and use of a variety of strategies to increase awareness about hereditary cancer risk and availability of clinical genetic services. Important barriers were identified regarding family cancer history communication and cancer prevention services. Strategies were suggested for communicating cancer genetic information to increase awareness and overcome these barriers; these included both targeted and tailored approaches. Conclusion: This research suggests that cancer genetic communication efforts should consider community and cultural perspectives as well as health care access issues before widespread implementation. Genet Med 2010:12(2):105-115.