Publications by authors named "Sancy A Leachman"

137 Publications

Nuclear receptor coactivator NCOA3 regulates ultraviolet radiation-induced DNA damage and melanoma susceptibility.

Cancer Res 2021 Mar 25. Epub 2021 Mar 25.

Cancer Center, CPMC Research Institute

Melanoma occurs as a consequence of inherited susceptibility to the disease and exposure to ultraviolet radiation (UVR) and is characterized by uncontrolled cellular proliferation and a high mutational load. The precise mechanisms by which UVR contributes to the development of melanoma remain poorly understood. Here we show that activation of nuclear receptor coactivator 3 (NCOA3) promotes melanomagenesis through regulation of UVR sensitivity, cell cycle progression, and circumvention of the DNA damage response (DDR). Downregulation of NCOA3 expression, either by genetic silencing or small molecule inhibition, significantly suppressed melanoma proliferation in melanoma cell lines and patient-derived xenografts. NCOA3 silencing suppressed expression of xeroderma pigmentosum C and increased melanoma cell sensitivity to UVR. Suppression of NCOA3 expression led to activation of DDR effectors and reduced expression of cyclin B1, resulting in G2/M arrest and mitotic catastrophe. A single nucleotide polymorphism in NCOA3 (T960T) reduced NCOA3 protein expression and was associated with decreased melanoma risk, given a significantly lower prevalence in a familial melanoma cohort than in a control cohort without cancer. Overexpression of wild-type NCOA3 promoted melanocyte survival following UVR and was accompanied by increased levels of UVR-induced DNA damage, both of which were attenuated by overexpression of NCOA3 (T960T). These results describe NCOA3-regulated pathways by which melanoma can develop with germline NCOA3 polymorphisms in the setting of UVR exposure, enabling enhanced melanocyte survival despite an increased mutational burden. They also identify NCOA3 as a novel therapeutic target for melanoma.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3450DOI Listing
March 2021

Melanoma toolkit for early detection (MTED) for primary care providers: A pilot study.

Pigment Cell Melanoma Res 2021 Feb 26. Epub 2021 Feb 26.

Oregon Health and Science University, Department of Dermatology.

Introduction: Primary care providers have greater access to patients despite often lacking the appropriate training or time to implement effective skin cancer screenings in their busy practices. Through collaborative efforts with Oregon's War on Melanoma public health campaign and other primary care trainings, we created "Melanoma Toolkit for Early Detection" (MTED): a training curriculum and resource repository for primary care providers.

Methods And Results: MTED consisted of three self-paced modules. Each participant completed a pre- and post-test consisting of demographic, confidence, and image identification questions. A subsequent optional 6-month follow-up image identification test was also provided. Of the 96 participants, 40 completed all the modules, the pre, and post-test. On average, scores increased by 6.0 (95% CI: 3.5 to 8.6) percentage points (P<0.001, paired t-test). The percent of participants reporting confidence with melanoma identification increased significantly from the pre- (23.3%) to the post-test (67.4%), an increase of 44.2 (95% CI: 29.3 to 59.0,) percentage points (P<0.001, McNemar's test).

Discussion: This study shows that an online curriculum such as MTED has the potential to increase PCPs confidence and knowledge. This could subsequently lead to improved early melanoma diagnosis by primary care providers.
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http://dx.doi.org/10.1111/pcmr.12968DOI Listing
February 2021

Clinical challenges in interpreting multiple pathogenic mutations in single patients.

Hered Cancer Clin Pract 2021 Feb 4;19(1):15. Epub 2021 Feb 4.

Department of Dermatology, Oregon Health & Science University, 3303 SW Bond Ave, Suite 16D, Portland, OR, 97239, USA.

Background: In the past two decades, genetic testing for cancer risk assessment has entered mainstream clinical practice due to the availability of low-cost panels of multiple cancer-associated genes. However, the clinical value of multiple-gene panels for cancer susceptibility is not well established, especially in cases where panel testing identifies more than one pathogenic variant. The risk for specific malignancies as a result of a mutated gene is complex and likely influenced by superimposed modifier variants and/or environmental effects. Recent data suggests that the combination of multiple pathogenic variants may be fewer than reported by chance, suggesting that some mutation combinations may be detrimental. Management of patients with "incidentally" discovered mutations can be particularly challenging, especially when established guidelines call for radical procedures (e.g. total gastrectomy in CDH1) in patients and families without a classic clinical history concerning for that cancer predisposition syndrome.

Case Presentation: We present two cases, one of an individual and one of a family, with multiple pathogenic mutations detected by multi-gene panel testing to highlight challenges practitioners face in counseling patients about pathogenic variants and determining preventive and therapeutic interventions.

Conclusions: Ongoing investigation is needed to improve our understanding of inherited susceptibility to disease in general and cancer predisposition syndromes, as this information has the potential to lead to the development of more precise and patient-specific counseling and surveillance strategies. The real-world adoption of new or improved technologies into clinical practice frequently requires medical decision-making in the absence of established understanding of gene-gene interactions. In the meantime, practitioners must be prepared to apply a rationale based on currently available knowledge to clinical decision-making. Current practice is evolving to rely heavily on clinical concordance with personal and family history in making specific therapeutic decisions.
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http://dx.doi.org/10.1186/s13053-021-00172-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863461PMC
February 2021

The State of Melanoma: Emergent Challenges and Opportunities.

Clin Cancer Res 2021 Jan 7. Epub 2021 Jan 7.

Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute

Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike - prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for melanoma patients and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome and offer recommendations for the best path forward.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4092DOI Listing
January 2021

Dermoscopy Proficiency Expectations for US Dermatology Resident Physicians: Results of a Modified Delphi Survey of Pigmented Lesion Experts.

JAMA Dermatol 2021 Feb;157(2):189-197

The Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, New York.

Importance: Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know.

Objectives: To identify consensus-based learning constructs representing an appropriate foundational proficiency in dermoscopic image interpretation for dermatology resident physicians, including dermoscopic diagnoses, associated features, and representative teaching images. Defining these foundational proficiency learning constructs will facilitate further skill development in dermoscopic image interpretation to help residents achieve clinical proficiency.

Design, Setting, And Participants: A 2-phase modified Delphi surveying technique was used to identify resident learning constructs in 3 sequential sets of surveys-diagnoses, features, and images. Expert panelists were recruited through an email distributed to the 32 members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group. Twenty-six (81%) opted to participate. Surveys were distributed using RedCAP software.

Main Outcomes And Measures: Consensus on diagnoses, associated dermoscopic features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for US dermatology resident physicians.

Results: Twenty-six pigmented lesion and dermoscopy specialists completed 8 rounds of surveys, with 100% (26/26) response rate in all rounds. A final list of 32 diagnoses and 116 associated dermoscopic features was generated. Three hundred seventy-eight representative teaching images reached consensus with panelists.

Conclusions And Relevance: Consensus achieved in this modified Delphi process identified common dermoscopic diagnoses, associated features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for dermatology residency training. This list of validated objectives provides a consensus-based foundation of key learning points in dermoscopy to help resident physicians achieve clinical proficiency in dermoscopic image interpretation.
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http://dx.doi.org/10.1001/jamadermatol.2020.5213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788510PMC
February 2021

Strategizing Screening for Melanoma in an Era of Novel Treatments: A Model-Based Approach.

Cancer Epidemiol Biomarkers Prev 2020 Dec 21;29(12):2599-2607. Epub 2020 Sep 21.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: Benefit-harm tradeoffs of melanoma screening depend on disease risk and treatment efficacy. We developed a model to project outcomes of screening for melanoma in populations with different risks under historic and novel systemic treatments.

Methods: Computer simulation model of a screening program with specified impact on overall and advanced-stage incidence. Inputs included meta-analyses of treatment trials, cancer registry data, and a melanoma risk prediction study RESULTS: Assuming 50% reduction in advanced stage under screening, the model projected 59 and 38 lives saved per 100,000 men under historic and novel treatments, respectively. With 10% increase in stage I, the model projects 2.9 and 4.7 overdiagnosed cases per life saved and number needed to be screened (NNS) equal to 1695 and 2632 under historical and novel treatments. When screening was performed only for the 20% of individuals with highest predicted risk, 34 and 22 lives per 100,000 were saved under historic and novel treatments. Similar results were obtained for women, but lives saved were lower.

Conclusions: Melanoma early detection programs must shift a substantial fraction of cases from advanced to localized stage to be sustainable. Advances in systemic therapies for melanoma might noticeably reduce benefits of screening, but restricting screening to individuals at highest risk will likely reduce intervention efforts and harms while preserving >50% of the benefit of nontargeted screening.

Impact: Our accessible modeling framework will help to guide population melanoma screening programs in an era of novel treatments for advanced disease.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0881DOI Listing
December 2020

Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit.

JAMA Dermatol 2020 09;156(9):1004-1011

Stanford University Medical Center and Cancer Institute, Stanford, California.

Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care.

Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies.

Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed.

Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility.

Conclusions And Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.
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http://dx.doi.org/10.1001/jamadermatol.2020.1729DOI Listing
September 2020

Reply to: Comments on "Proposed approach for reusing surgical masks in COVID-19 pandemic".

J Am Acad Dermatol 2020 09 22;83(3):e229. Epub 2020 May 22.

Department of Dermatology, Oregon Health & Science University, Portland, Oregon. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.05.084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242196PMC
September 2020

Priority of Risk (But Not Perceived Magnitude of Risk) Predicts Improved Sun-Protection Behavior Following Genetic Counseling for Familial Melanoma.

Ann Behav Med 2021 02;55(1):24-40

Oregon Health & Science University, Portland, OR.

Background: Understanding multiple components of risk perceptions is important because perceived risk predicts engagement in prevention behaviors.

Purpose: To examine how multiple components of risk perceptions (perceived magnitude of and worry about risk, prioritization of the management of one's risk) changed following genetic counseling with or without test reporting, and to examine which of these components prospectively predicted improvements in sun-protection behavior 1 year later.

Methods: A prospective, nonrandomized study design was used. Participants were 114 unaffected members of melanoma-prone families who (i) underwent genetic testing for a CDKN2A/p16 mutation (n = 69) or (ii) were at comparably elevated risk based on family history and underwent genetic counseling but not testing (no-test controls, n = 45). Participants reported risk perception components and sun-protection behavior at baseline, immediately following counseling, and 1 month and 1 year after counseling.

Results: Factor analysis indicated three risk components. Carriers reported increased perceived magnitude and priority of risk, but not cancer worry. No-test controls showed no changes in any risk perception. Among noncarriers, priority of risk remained high at all assessments, whereas magnitude of risk and cancer worry decreased. Of the three risk components, greater priority of risk uniquely predicted improved self-reported sun protection 1 year post-counseling.

Conclusions: Priority of risk (i) seems to be a component of risk perceptions distinguishable from magnitude of risk and cancer worry, (ii) may be an important predictor of daily prevention behavior, and (iii) remained elevated 1 year following genetic counseling only for participants who received a positive melanoma genetic test result.
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http://dx.doi.org/10.1093/abm/kaaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880221PMC
February 2021

Proposed approach for reusing surgical masks in COVID-19 pandemic.

J Am Acad Dermatol 2020 Jul 26;83(1):e53-e54. Epub 2020 Apr 26.

Department of Dermatology, Oregon Health & Science University, Portland, Oregon. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.04.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194514PMC
July 2020

Parent and child perspectives on family interactions related to melanoma risk and prevention after CDKN2A/p16 testing of minor children.

J Community Genet 2020 Jul 18;11(3):321-329. Epub 2020 Jan 18.

Department of Dermatology, Oregon Health & Science University, Portland, USA.

Predispositional genetic testing of children for adult-onset health risks is typically only used when prevention and screening measures have utility during childhood. Little is known about how children and their parents may use predispositional risk information, including whether it changes their interactions around risk-reducing prevention and screening behaviors. The current study examined perspectives on family interactions around skin cancer prevention and control practices through 1 year after test reporting and counseling among children who received melanoma predispositional genetic testing and their parents. Eighteen children (50% carriers, 56% male, mean age = 12.4 years) and 11 parents from 11 families participated in semi-structured interviews 1 month and 1 year after receiving the child's test result. Both parents (73%) and children (50%) reported making changes to family skin cancer prevention and control practices after receiving the test result. Parent- and child-reported discussions about melanoma prevention increased over time (36% parents and 61% children at 1 month, 73% parents and 67% at 1 year). One-quarter (27%) of parents and no children reported having conflicts about sun protection or screening 1 year after test reporting. A majority of parents (63%) reported treating their child differently at the 1-year follow-up, especially among carriers. Predispositional genetic testing for melanoma was associated with reported changes to plans for and discussions about sun protection, and high levels of parent-child collaboration to implement child sun protection. Future work could seek to identify child and parent factors and interactions that predict improved prevention and screening behaviors following pediatric predispositional genetic testing.
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http://dx.doi.org/10.1007/s12687-020-00453-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295919PMC
July 2020

Prognostic gene expression profiling in melanoma: necessary steps to incorporate into clinical practice.

Melanoma Manag 2019 Dec 17;6(4):MMT32. Epub 2019 Dec 17.

Dermatology, Stanford University Medical Center & Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94305, USA.

Prognostic gene expression profiling (GEP) tests for cutaneous melanoma (CM) are not recommended in current guidelines outside of a clinical trial. However, their use is becoming more prevalent and some practitioners are using GEP tests to guide patient management. Thus, there is an urgent need to bridge this gap between test usage and clinical guideline recommendations by obtaining high-quality evidence to guide us toward best practice use of GEP testing in CM patients. We focus here on the opportunities and uncertainties associated with prognostic GEP testing in CM, review how GEP testing was incorporated into clinical care guidelines for uveal melanoma and breast cancer and discuss the role of clinical trials to determine best use in patients with CM.
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http://dx.doi.org/10.2217/mmt-2019-0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920745PMC
December 2019

A pilot study of a telehealth family-focused melanoma preventive intervention for children with a family history of melanoma.

Psychooncology 2020 01 10;29(1):148-155. Epub 2019 Nov 10.

Cancer Control Program, Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C.

Objective: Melanoma preventive interventions for children with familial risk are critically needed because ultraviolet radiation (UVR) exposure and sunburn occurrence early in life are the primary modifiable risk factors for melanoma. The current study examined the feasibility and acceptability of a new, family-focused telehealth intervention for children with familial risk for melanoma and their parents. The study also explored changes in child sun protection and risk behaviors, sunburn occurrence, and objectively measured UVR exposure.

Methods: This was a prospective study with a single-group design (n = 21 parent-child dyads, children ages 8-17). Dyads were asked to participate in three in-person assessments and three live video teleconference intervention sessions.

Results: The intervention was feasibly delivered, and the intervention content was acceptable to parents and children. The intervention was associated with improvements in child use of certain sun protection strategies over time and declines in child UVR exposure.

Conclusions: A telehealth-delivered,family-focused melanoma preventive intervention was feasibly delivered and was acceptable to parent-child dyads. Future melanoma preventive interventions for this at-risk population could incorporate eHealth technologies to facilitate improvements in use of sun protection and monitoring of UVR exposure. This trial was registered with Clinicaltrials.gov, number NCT02846714.
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http://dx.doi.org/10.1002/pon.5232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980884PMC
January 2020

Use of new molecular tests for melanoma by pigmented-lesion experts.

J Am Acad Dermatol 2020 01 13;82(1):245-247. Epub 2019 Aug 13.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City; Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City; Department of Oncological Sciences, University of Utah Health Sciences Center, Salt Lake City. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2019.08.022DOI Listing
January 2020

CDKN2A testing and genetic counseling promote reductions in objectively measured sun exposure one year later.

Genet Med 2020 01 2;22(1):26-34. Epub 2019 Aug 2.

Oregon Health and Science University, Portland, OR, USA.

Purpose: This study investigated whether genetic counseling and test reporting for the highly penetrant CDKN2A melanoma predisposition gene promoted decreases in sun exposure.

Methods: A prospective, nonequivalent control group design compared unaffected participants (N = 128, M = 35.24, 52% men) from (1) families known to carry a CDKN2A pathogenic variant, who received counseling about management recommendations and a positive or negative genetic test result and (2) no-test control families known not to carry a CDKN2A pathogenic variant, who received equivalent counseling based on their comparable family history. Changes in daily ultraviolet radiation (UVR) exposure (J/m), skin pigmentation (melanin index), and sunburns between baseline and one year following counseling were compared among carriers (n = 32), noncarriers (n = 46), and no-test control participants (n = 50).

Results: Both carriers and no-test control participants exhibited a decrease one year later in daily UVR dose (B = -0.52, -0.33, p < 0.01). Only carriers exhibited a significant decrease in skin pigmentation at the wrist one year later (B = -0.11, p < 0.001), and both carriers and no-test control participants reported fewer sunburns than noncarriers (p < 0.05). Facial pigmentation did not change for any group. Noncarriers did not change on any measure of UVR exposure.

Conclusions: These findings support the clinical utility of disclosing CDKN2A test results and providing risk management education to high-risk individuals.
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http://dx.doi.org/10.1038/s41436-019-0608-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946876PMC
January 2020

Melanoma to Vitiligo: The Melanocyte in Biology & Medicine-Joint Montagna Symposium on the Biology of Skin/PanAmerican Society for Pigment Cell Research Annual Meeting.

J Invest Dermatol 2020 02 23;140(2):269-274. Epub 2019 Jul 23.

Department of Dermatology, Oregon Health & Science University, Portland, Oregon; Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, Oregon. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2019.03.1164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981008PMC
February 2020

A four-group experiment to improve Western high school students' sun protection behaviors.

Transl Behav Med 2019 05;9(3):468-479

Cancer Prevention and Control Program, Georgetown Lombardi Comprehensive Cancer Center, NW Washington, DC, USA.

Multicomponent skin cancer preventive interventions for adolescents that aim to decrease ultraviolet radiation (UVR) exposure and sunburns are particularly needed given their intentional tanning and infrequent use of sun protection. The purpose of this study was to conduct an early-phase study within the Multiphase Optimization Strategy framework that experimentally tested four unique intervention components targeting high school students' skin cancer prevention behaviors. Schools (11 total, N = 1,573 students) were assigned to receive one of four interventions: skin cancer education (control), education plus a sunscreen activity (to illustrate sunscreen's UVR-blocking properties), or behavior change worksheet (sun protection goal setting and planning) or receipt of a personalized UV damage photograph (photograph of facial damage). Sun protection, sunburn, and tanning outcomes were assessed before intervention and at 1-month follow-up. Within- and between-intervention changes in outcomes were examined using generalized estimating equation modeling. All interventions were associated with significant improvements in sun protection. The photograph was superior in controlling intentional tanning and sunburn when compared to the behavior change worksheet (ps < .05). In contrast, the worksheet was associated with greater increases in sun protection use when compared with the photograph (ps < .05). In this experiment testing four skin cancer preventive intervention components that varied in approach, content, and interactivity, the behavior change worksheet was superior in improving sun protection use whereas the UV photograph was superior in controlling intentional tanning and sunburn. Future randomized trials to test combinations of these intervention components are needed, and could identify mechanisms underlying improved effects and demographic or behavioral moderators of intervention effects.
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http://dx.doi.org/10.1093/tbm/ibz021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520801PMC
May 2019

MoleMapper: an application for crowdsourcing mole images to advance melanoma early-detection research.

Semin Cutan Med Surg 2019 Mar 1;38(1):E49-E56. Epub 2019 Mar 1.

Department of Dermatology, Oregon Health & Science University, Portland, Oregon.

Advancements in smartphone technologies and the use of specialized health care applications offer an exciting new era to promote melanoma awareness to the public and improve education and prevention strategies. These applications also afford an opportunity to power meaningful research aimed at improving image diagnostics and early melanoma detection. Here, we summarize our experience associated with developing and managing the implementation of MoleMapper™, a research-based application that not only provides an efficient way for users to digitally track images of moles and facilitate skin self-examinations but also provides a platform to crowdsource research participants and the curation of mole images in efforts to advance melanoma research. Obtaining electronic consent, safeguarding participant data, and employing a framework to ensure collection of meaningful data represent a few of the inherent difficulties associated with orchestrating such a wide-scale research enterprise. In this review, we discuss strategies to overcome these and other challenges leading to the implementation of MoleMapper™.
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http://dx.doi.org/10.12788/j.sder.2019.001DOI Listing
March 2019

Parent and child perspectives on perceived barriers to child sun protection and their association with sun protection strategies among children of melanoma survivors.

Pediatr Dermatol 2019 May 20;36(3):317-323. Epub 2019 Mar 20.

Department of Dermatology & Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.

Background/objectives: Children with an elevated familial risk for melanoma inconsistently implement sun protection behaviors that could mitigate their melanoma risk. Little is known about perceived barriers to child sun protection among this at-risk group and their parents, and the extent to which perceived barriers are associated with child sun protection. The goal of this study was to examine, among children with a family history of melanoma, the frequency with which children and their parents reported barriers to child sun protection and the extent to which barriers were associated with reported use of sun protection among children.

Methods: Children with a family history of melanoma and their parents completed questionnaires assessing perceived barriers and reported child use of sun protection.

Results: Common barriers to child sun protection included being bothered by implementing the behavior or forgetting. A greater number of perceived barriers were associated with less frequent child use of sunscreen, long-sleeved shirts, long pants, and shade.

Conclusions: Children at elevated risk for melanoma due to a family history of the disease and their parents perceive multiple barriers to sun protection that are associated with children's use of these melanoma preventive behaviors. Sun protection interventions for this at-risk population could provide families with specific strategies to address common barriers to implementing child sun protection.
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http://dx.doi.org/10.1111/pde.13796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525049PMC
May 2019

Understanding Skin Screening Practices Among Children at Elevated Risk for Melanoma to Inform Interventions for Melanoma Prevention and Control.

J Cancer Educ 2020 06;35(3):509-514

Huntsman Cancer Institute, 2000 Circle of Hope, Rm 4509, Salt Lake City, UT, 84112, USA.

Melanoma is the deadliest form of skin cancer. Screening can aid in early disease detection, when treatment is more effective. Although there are currently no consensus guidelines regarding skin screening for pediatric populations with elevated familial risk for melanoma, at-risk children with the help of their parents and healthcare providers may implement skin self-exams. Healthcare providers may also recommend screening practices for these children. The goal of the current study was to describe current screening behaviors and provider recommendation for screening among children of melanoma survivors. Parents of children with a family history of melanoma completed a questionnaire that included items on children's screening frequency, thoroughness, and who performed the screening. Seventy-four percent of parents reported that their children (mean age = 9.0 years, SD = 4.8) had engaged in parent-assisted skin self-exams (SSEs) in the past 6 months. Only 12% of parents reported that children received SSEs once per month (the recommended frequency for adult melanoma survivors). In open-ended responses, parents reported that healthcare providers had provided recommendations around how to conduct SSEs, but most parents did not report receiving information on recommended SSE frequency. Twenty-six percent of parents (n = 18) reported that children had received a skin exam by a healthcare provider in the past 6 months. The majority of children with a family history of melanoma are reportedly engaging in skin exams despite the lack of guidelines on screening in this population. Future melanoma preventive interventions should consider providing families guidance about implementing screening with their children.
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http://dx.doi.org/10.1007/s13187-019-01489-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697232PMC
June 2020

Reply to Reimann et al.

Mod Pathol 2019 05 21;32(5):725-727. Epub 2019 Jan 21.

Department of Pathology, Oregon Health & Science University, Portland, OR, USA.

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http://dx.doi.org/10.1038/s41379-018-0197-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760647PMC
May 2019

Melanoma Early Detection: Big Data, Bigger Picture.

J Invest Dermatol 2019 01 25;139(1):25-30. Epub 2018 Oct 25.

Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA; Melanoma Program, Knight Cancer Institute at Oregon Health & Science University, Portland, Oregon, USA. Electronic address:

Innovative technologies, including novel communication and imaging tools, are affecting dermatology in profound ways. A burning question for the field is whether we will retrospectively react to innovations or proactively leverage them to benefit precision medicine. Early detection of melanoma is a dermatologic area particularly poised to benefit from such innovation. This session of the Montagna Symposium on Biology of Skin focused on provocative, potentially disruptive advances, including crowdsourcing of patient advocacy efforts, rigorous experimental design of public education campaigns, research with mobile phone applications, advanced skin imaging technologies, and the emergence of artificial intelligence as a diagnostic supplement.
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http://dx.doi.org/10.1016/j.jid.2018.06.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685706PMC
January 2019

Frontiers in pigment cell and melanoma research.

Pigment Cell Melanoma Res 2018 11 3;31(6):728-735. Epub 2018 Oct 3.

Department of Dermatology, University of Colorado Denver, Aurora, Colorado.

In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution.
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http://dx.doi.org/10.1111/pcmr.12728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701837PMC
November 2018

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials.

Cancer 2019 01 3;125(1):18-44. Epub 2018 Oct 3.

Department of Dermatology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.
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http://dx.doi.org/10.1002/cncr.31719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860362PMC
January 2019

Mineral sunscreens not recommended by Consumer Reports: Suggestions to improve the review process.

J Am Acad Dermatol 2019 03 18;80(3):832-833. Epub 2018 Sep 18.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah; Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah; Department of Oncological Sciences, University of Utah, Salt Lake City, Utah. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2018.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479990PMC
March 2019

Daily Minutes of Unprotected Sun Exposure (MUSE) Inventory: Measure description and comparisons to UVR sensor and sun protection survey data.

Prev Med Rep 2018 Sep 24;11:305-311. Epub 2018 Jul 24.

Department of Dermatology, Northwestern University Feinberg School of Medicine, 645 N Michigan Ave, Suite 1050, Chicago, IL 60611, USA.

One in five US adults will be diagnosed with skin cancer. As most skin cancers are attributable to sun exposure, this risk factor is an important target for research and intervention. Most sun exposure measures assess frequency of specific sun-protection behaviors, which does not account for the use of multiple, potentially overlapping sun-protection methods. In contrast, the Daily Minutes of Unprotected Sun Exposure (MUSE) Inventory assesses sun-protection behavior during self-reported activities, providing several useful metrics, including duration of unprotected sun exposure on 17 body sites, combined to yield an overall MUSE score weighted by percent of body exposed. The present study was conducted July-September 2017, in Chicago, IL USA. For 10 days, participants (39 melanoma survivors;  = 58.59, 64.5% female) wore an ultraviolet radiation (UVR) sensor and completed the Daily MUSE Inventory each evening. The Sun Habits Survey was completed at the end of the study. Outdoor time reported in the MUSE Inventory significantly predicted outdoor time recorded by UVR sensors,  = 0.53,  < .001. For all sun-protection behaviors except shade, reports from the Daily MUSE Inventory (i.e., percentage of outdoor time a particular strategy was used) correlated with frequency ratings of the same strategy from the Sun Habits Survey (s = 0.66-0.75,  < .05). In sum, the Daily MUSE Inventory corresponds with sensor and survey data, and provides a novel metric of unprotected sun exposure that will be useful for evaluating overall extent of sun exposure, including exposure on several smaller body sites that are at high risk for skin cancer.
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http://dx.doi.org/10.1016/j.pmedr.2018.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092553PMC
September 2018

Evaluation of Biodistribution of Sulforaphane after Administration of Oral Broccoli Sprout Extract in Melanoma Patients with Multiple Atypical Nevi.

Cancer Prev Res (Phila) 2018 07 24;11(7):429-438. Epub 2018 Apr 24.

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.

Broccoli sprout extract containing sulforaphane (BSE-SFN) has been shown to inhibit ultraviolet radiation-induced damage and tumor progression in skin. This study evaluated the toxicity and potential effects of oral BSE-SFN at three dosages. Seventeen patients who each had at least 2 atypical nevi and a prior history of melanoma were randomly allocated to 50, 100, or 200 μmol oral BSE-SFN daily for 28 days. Atypical nevi were photographed on days 1 and 28, and plasma and nevus samples were taken on days 1, 2, and 28. Endpoints assessed were safety, plasma and skin sulforaphane levels, gross and histologic changes, IHC for phospho-STAT3(Y705), Ki-67, Bcl-2, HMOX1, and TUNEL, plasma cytokine levels, and tissue proteomics. All 17 patients completed 28 days with no dose-limiting toxicities. Plasma sulforaphane levels pooled for days 1, 2, and 28 showed median postadministration increases of 120 ng/mL for 50 μmol, 206 ng/mL for 100 μmol, and 655 ng/mL for 200 μmol. Median skin sulforaphane levels on day 28 were 0.0, 3.1, and 34.1 ng/g for 50, 100, and 200 μmol, respectively. Plasma levels of proinflammatory cytokines decreased from day 1 to 28. The tumor suppressor decorin was increased from day 1 to 28. Oral BSE-SFN is well tolerated at daily doses up to 200 μmol and achieves dose-dependent levels in plasma and skin. A larger efficacy evaluation of 200 μmol daily for longer intervals is now reasonable to better characterize clinical and biological effects of BSE-SFN as chemoprevention for melanoma. .
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http://dx.doi.org/10.1158/1940-6207.CAPR-17-0268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030491PMC
July 2018

Barriers and Facilitators to Melanoma Prevention and Control Behaviors Among At-Risk Children.

J Community Health 2018 10;43(5):993-1001

Department of Dermatology & Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.

Melanoma prevention is essential for children who are at elevated risk for the disease due to family history. However, children who carry a familial risk for the disease do not optimally adhere to recommended melanoma preventive behaviors. The current study sought to identify perceived barriers to and facilitators of children's engagement in melanoma preventive behaviors among children at elevated risk for melanoma due to family history of the disease (i.e., having a parent with a history of melanoma) from both parents' and childrens' perspectives. Qualitative methods were employed and consisted of separate focus group discussions with children (ages 8-17 years, n = 37) and their parents (n = 39). Focus group transcripts were coded using content analysis. Parents and children reported a number of barriers and facilitators, including on the individual (e.g., knowledge and awareness, preferences), social (e.g., peer influences, family modeling and communication), and contextual (e.g., healthcare provider communication) levels. The identified categories of barriers and facilitators both confirm and extend the literature documenting the reasons children who are at elevated risk for melanoma do not engage in melanoma prevention and control behaviors. Programs aiming to decrease melanoma risk among children of melanoma survivors could help families address their barriers to preventive behavior implementation and build on facilitators. Melanoma survivors and their children could benefit from support on their interactions with healthcare providers, schools, peers, and other caregivers about melanoma prevention.
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http://dx.doi.org/10.1007/s10900-018-0516-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119479PMC
October 2018

Montagna Symposium 2017-Precision Dermatology: Next Generation Prevention, Diagnosis, and Treatment.

J Invest Dermatol 2018 06 2;138(6):1243-1248. Epub 2018 May 2.

Department of Dermatology, Oregon Health and Science University, Portland, Oregon, USA; Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2018.02.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970097PMC
June 2018

Genetic test reporting of CDKN2A provides informational and motivational benefits for managing melanoma risk.

Transl Behav Med 2018 01;8(1):29-43

Oregon Health and Science University, Portland, OR, USA.

A CDKN2A/p16 mutation confers 28%-67% lifetime melanoma risk, a risk that may be moderated by ultraviolet radiation exposure. The aim of this study was to test whether melanoma genetic counseling and test disclosure conferred unique informational, motivational, or emotional benefits compared to family history-based counseling. Participants included were 114 unaffected members of melanoma-prone families, ages 16-69, 51.8% men, 65.8% with minor children or grandchildren. Carriers (n = 28) and noncarriers (n = 41) from families with a CDKN2A mutation were compared to no-test controls (n = 45) from melanoma-prone families without an identifiable CDKN2A mutation. All participants received equivalent counseling about melanoma risk and management; only CDKN2A participants received genetic test results. Using newly developed inventories, participants rated perceived costs and benefits for managing their own and their children's or grandchildren's melanoma risk 1 month and 1 year after counseling. Propensity scores controlled for baseline family differences. Compared to no-test controls, participants who received test results (carriers and noncarriers) reported feeling significantly more informed and prepared to manage their risk, and carriers reported greater motivation to reduce sun exposure. All groups reported low negative emotions about melanoma risk. Parents reported high levels of preparedness to manage children's risk regardless of group. Carrier parents reported greater (but moderate) worry about their children's risk than no-test control parents. Women, older, and more educated respondents reported greater informational and motivational benefits regardless of group. Genetic test results were perceived as more informative and motivating for personal sun protection efforts than equivalent counseling based on family history alone.
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http://dx.doi.org/10.1093/tbm/ibx011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065541PMC
January 2018