Cancer worry among BRCA1/2 pathogenic variant carriers choosing surgery to prevent tubal/ovarian cancer: course over time and associated factors

Objective High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers undergoing surgery to prevent ovarian cancer, and identified factors associated with high cancer worry. Methods Cancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose either novel risk-reducing salpingectomy with delayed oophorectomy or standard risk-reducing salpingo-oophorectomy. The Cancer Worry Scale was obtained before and 3 and 12 months after surgery. Cancer worry patterns were analysed using latent class growth analysis and associated factors were identified with regression analysis. Results Of all 577 BRCA1/2-PV carriers, 320 (57%) had high (≥ 14) cancer worry pre-surgery, and 54% had lower worry 12 months post-surgery than pre-surgery. Based on patterns over time, BRCA1/2-PV carriers could be classified into three groups: persistently low cancer worry (56%), persistently high cancer worry (6%), and fluctuating, mostly declining, cancer worry (37%). Factors associated with persistently high cancer concerns were age below 35 (BRCA1) or 40 (BRCA2), unemployment, previous breast cancer, lower education and a more recent BRCA1/2-PV diagnosis. Conclusions Some degree of cancer worry is considered normal, and most BRCA1/2-PV carriers have declining cancer worry after gynaecological risk-reducing surgery. However, a subset of these BRCA1/2-PV carriers has persisting major cancer concerns up to 1 year after surgery. They should be identified and potentially offered additional support. Clinical trial registration The TUBA-study is registered at ClinicalTrials.gov since December 11th, 2014. Registration number: NCT02321228.

A Randomized Clinical Trial of Precision Prevention Materials Incorporating MC1R Genetic Risk to Improve Skin Cancer Prevention Activities Among Hispanics

Purpose: Skin cancer incidence is increasing among Hispanics, who experience worse outcomes than non-Hispanic Whites. Precision prevention incorporating genetic testing for (melanocortin-1 receptor) MC1R, a skin cancer susceptibility marker, may improve prevention behavior. Experimental Design: Hispanic participants (n = 920) from Tampa, FL and Ponce, PR, were block-randomized within MC1R higher- and average-risk groups to precision prevention or generic prevention arms. We collected baseline information on demographics, family history of cancer, phenotypic characteristics, health literacy, health numeracy, and psychosocial measures. Participants reported weekday and weekend sun exposure (in hours), number of sunburns, frequency of five sun protection behaviors, intentional outdoor and indoor tanning, and skin examinations at baseline, 3 months, and 9 months. Participants also reported these outcomes for their eldest child ≤10 years old. Results: Among MC1R higher-risk participants, precision prevention increased sunscreen use (OR = 1.74, P = 0.03) and receipt of a clinical skin exam (OR = 6.51, P = 0.0006); and it decreased weekday sun exposure hours (β = −0.94, P = 0.005) and improved sun protection behaviors (β = 0.93, P = 0.02) in their children. There were no significant intervention effects among MC1R average-risk participants. The intervention did not elevate participant cancer worry. We also identified moderators of the intervention effect among both average- and higher-risk participants. Conclusions: Receipt of MC1R precision prevention materials improved some skin cancer prevention behaviors among higher-risk participants and their children and did not result in reduced prevention activities among average-risk participants. Despite these encouraging findings, levels of sun protection behaviors remained suboptimal among participants, warranting more awareness and prevention campaigns targeted to Hispanics Significance: Our results support a precision public health approach to reducing skin cancers among Hispanics, an underserved population in precision medicine, and may additionally improve preventive behaviors among their children.

High Prevalence of Monoclonal Gammopathy in a Population at Risk: The First Results of the Promise Study

Background Multiple myeloma (MM) evolves from monoclonal gammopathy of undetermined significance (MGUS), a clinically detectable but asymptomatic premalignant phase seen in ~3% of the general population 50 years of age or older. The prevalence of MGUS has not been described in a population at high risk of developing MM, specifically Black/African American (AA) individuals or first-degree relatives of patients with hematologic malignancies (HM). In 2019, we launched the first nationwide US screening study for individuals at high risk of MM to help better identify what population would benefit most from screening and early intervention for precursor MM stages. We aim to assess the prevalence of MGUS in a population at high risk of MM and characterize clinical variables of individuals who screen positive. Here, we report interim screening data on the first 2,960 participants. Methods Individuals aged 40 or older with an additional MM risk factor are eligible to be screened in the PROMISE Study. High-risk individuals include Black/AAs and those with a first-degree relative diagnosed with a hematologic malignancy or a precursor condition to MM. Blood from all participants was analyzed via serum protein electrophoresis, immunofixation, and Optilite® to measure the serum free light chains (sFLC), IgG, IgA and IgM. Results were returned to all participants, and those who tested positive for a monoclonal gammopathy (MGUS/SMM) were referred to a hematologist for clinical follow-up and invited to periodically complete epidemiologic exposure and psychosocial questionaries, including a 4-item cancer worry questionnaire and the RAND 36-item Short Form Survey (SF-36). To investigate the use of the higher-sensitivity matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) with the Optilite® IgG, IgA, IgM and sFLC results as a screening test for all participants, we rescreened 1,092 samples from PROMISE. The Binding Site Group proprietary software was used for the analysis of the combined MS/Optilite® results, allowing for the detection and quantification of M-protein. Heavy-Chain MGUS (HC-MGUS) was defined by the presence of one or more paired heavy and light chain monoclonal peaks detected by MS. Pairing was based on mass to charge ratio of identified peaks. To enrich the PROMISE cohort with Black/AA individuals, we identified and screened 1,868 Black/AA additional individuals from the Mass General Brigham (MGB) Biobank who met the PROMISE enrollment criteria. Screening was performed by MS/Optilite®, and results have not been returned to participants. Results We screened 2,960 participants with the combined MS/Optilite® approach. We report here the prevalence of HC-MGUS and plan on presenting the estimated rate of light chain MGUS in our cohort, at the meeting. We detected HC-MGUS in 9.6% (95% CI: 8.6-11%) of our cohort, with a prevalence of 10% (95% CI: 8.3-12%) in the PROMISE cohort and 9.4% (95% CI: 8.1-11%) in the MGB cohort (Table 1 and Figure 1). HC-MGUS prevalence increased with age in high-risk individuals from 4.9% (CI: 3.3-6.9%) for participants aged 40-49 to 13% (CI: 10-17%) in the 70-79 range (P < 1.2E-5). Among monoclonal HC-MGUS, we found 65% IgG, 18% IgM, and 18% IgA. M-spike was quantified in 97% of samples. Median M-spike concentration was, 0.058g/dL (max. 2.6g/dL) for IgG, 0.0043g/dL (max. 0.6g/dL) for IgM, and 0.067g/dL (max. 0.8g/dL) for IgA. In the Promise cohort, no significant change in cancer worry was observed across the pre- and post-screening interval among participants who screened positive (P = 0.52). Health-related quality of life, as measured by the SF-36, was not significantly different in screen-positive vs. screen-negative individuals for any of the eight subscales (all P > 0.20). Conclusions We present the largest dataset on monoclonal gammopathy prevalence and screening in individuals at high risk for MM, and more specifically the largest cohort of Black/AA, using a novel high-sensitivity testing approach. Our results confirm that older adults who are Black/AA or have a first-degree relative with an HM have a high prevalence MGUS and may benefit from precision screening approaches to allow for early detection and clinical intervention. Preliminary data on cancer worry and quality of life indicates that the psychosocial burden of screening in this population is likely minimal. Figure 1 Figure 1. Disclosures Sakrikar: The Binding Site: Current Employment. Krause: The Binding Site: Current Employment. Barnidge: The Binding Site: Current Employment. Bustoros: Takeda: Consultancy, Honoraria; Janssen, Bristol Myers Squibb: Honoraria, Speakers Bureau. Perkins: The Binding Site: Current Employment. Harding: The Binding Site: Current Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kapoor: Ichnos Sciences: Research Funding; Amgen: Research Funding; Pharmacyclics: Consultancy; Takeda: Research Funding; Sanofi: Consultancy; Regeneron Pharmaceuticals: Research Funding; AbbVie: Research Funding; BeiGene: Consultancy; Sanofi: Research Funding; Karyopharm: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Consultancy; Cellectar: Consultancy. Mo: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Eli Lilly: Consultancy; Janssen: Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Murray: The Binding Site: Patents & Royalties: Potential Royalties for use of mass spectrometry in M-protein detection. Getz: Scorpion Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; IBM, Pharmacyclics: Research Funding. Marinac: JBF Legal: Consultancy; GRAIL Inc: Research Funding. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy.

Association of Cancer Worry and Physical Activity Behaviors in Adults without Cancer

Background: Cancer worry has been conceptualized as a potential motivator to engage in cancer preventative behaviors like cancer screening, genetic testing, or smoking cessation. It is currently unknown if these findings extend to the domain of physical activity, as physical activity has been associated with decreased cancer risk. Objective: To examine if the association between cancer worry and other health behaviors will extend to physical activity in a sample of adults not diagnosed with cancer. Methods: Data are drawn from the NCI's 2017 Health Information National Trends Survey (HINTS) Iteration 5 Cycle 1 (N = 2,706) dataset, a nationally representative survey of adults in the United States. A KruskalWallis-H test was conducted to determine whether physical activity duration (i.e., daily minutes) differed between cancer worry levels with a post hoc Dunn's multiple comparison test to compare the differences between mean ranks. Results: A Kruskal-Wallis-H test showed statistically significant differences in PA duration (i.e., daily minutes) between groups that differed in their level of cancer worry. PA in minutes on a typical day was significantly lower in those who reported not at all, moderate, and extreme worry about developing cancer compared to those who reported slightly and somewhat worried. Conclusion: Contrary to our expectations, our results suggest that higher cancer worry levels are paradoxically associated with less PA. This study's results are significant in that they add to the breadth of literature linking cancer worry to health behaviors and may be used to inform future health promotion interventions.

Factors Affecting Cancer Prevention Behaviors and Cancer Screening in First-Degree Relatives of Breast and Colorectal Cancer Patients in Korea: A Cross-Sectional Study

BackgroundFirst-degree relatives (FDRs) of cancer patients have a high risk of cancer due to a similar lifestyle and genetic predisposition. However, previous studies rarely examined the level of cancer prevention behaviors and screening and affecting factors in cancer patients’ FDRs.PurposeThis study aimed to describe the levels of cancer knowledge, attitudes toward cancer, cancer worry, perceived cancer risk, and cancer prevention behaviors and cancer screening in FDRs of breast and colorectal cancer patients. Moreover, it sought to identify factors affecting cancer prevention behavior and cancer screening.MethodsA cross-sectional, descriptive correlational design was used. The study enrolled 138 FDRs of breast and colorectal cancer patients. Participants completed self-administered questionnaires at a tertiary hospital in Seoul, Korea. Descriptive statistics, frequencies, chi-square test, independent t test, one-way analysis of variance (ANOVA), Pearson’s correlation, multiple regression, and logistic regression were performed for data analysis.ResultsThe levels of perceived cancer risk, cancer knowledge, attitude toward cancer, and cancer prevention behaviors were moderate, while the level of cancer worry was high. Ninety-two participants reported having undergone cancer screenings, but the types of screening were not associated with their family history. Age, gender, and attitude toward cancer affected cancer prevention behaviors. The cancer screening rate was higher in older participants, in women, and in patients’ FDRs with a longer cancer diagnosis.Implications for PracticeAttitude was the modifiable factor for cancer prevention behaviors. Nurse-led educational and counseling interventions should be developed to improve attitude toward cancer among FDRs of cancer patients.

Effect of Educating Healthy Women About Breast Cancer on Their Fear of Breast Cancer and Breast Cancer Worry

Background Breast cancer (BC) is the most common cancer among females worldwide and prognosis depends on early diagnosis; however women seldom seek medical attention on time. Two of the important reasons for this delay are BC worry (BCW) and fear (BCF). We aimed to assess whether educating healthy women about BC could affect their BCF and BCW. Methods Participants were women above 18 years who visited the Breast Clinic who had a normal or benign breast assessment and were not suffering from any psychological disorder. They filled a survey including items of the hospital anxiety and depression scale (HADS), Lerman BCW scale and Champion BCF scale before and after the intervention. In the course of the study, 20 short educational videos about BC were sent to all of them by WhatsApp. Results The mean age of the 104 participants was 38.37 years. HADS scores showed a fairly good general psychological health of the participants before and after the intervention. The mean BCW and BCF score decreased significantly after vs. before the intervention. Conclusions Our study showed that educating healthy women about BC can effectively reduce BCF and BCW. We suggest that similar studies follow the participants in order to assess the effect on their health-seeking behaviour about BC in the long term.