Study protocol: a cluster randomized controlled trial of web-based decision support tools for increasing BRCA1/2 genetic counseling referral in primary care.

BACKGROUND: BRCA1 and BRCA2 mutations confer a substantial breast risk of developing breast cancer to those who carry them. For this reason, the United States Preventative Services Task Force (USPSTF) has recommended that all women be screened in the primary care setting for a family history indicative of a mutation, and women with strong family histories of breast or ovarian cancer be referred to genetic counseling. However, few high-risk women are being routinely screened and fewer are referred to genetic counseling. To address this need we have developed two decision support tools that are integrated into clinical care. METHOD: This study is a cluster randomized controlled trial of high-risk patients and their health care providers. Patient-provider dyads will be randomized to receive either standard education that is supplemented with the patient-facing decision aid, RealRisks, and the provider-facing Breast Cancer Risk Navigation Toolbox (BNAV) or standard education alone. We will assess these tools' effectiveness in promoting genetic counseling uptake and informed and shared decision making about genetic testing. DISCUSSION: If found to be effective, these tools can help integrate genomic risk assessment into primary care and, ultimately, help expand access to risk-appropriate breast cancer prevention options to a broader population of high-risk women. TRIAL REGISTRATION: This trial is retrospectively registered with ClinicalTrials.gov Identifier: NCT03470402 : 20 March 2018.

Pilot study of decision support tools on breast cancer chemoprevention for high-risk women and healthcare providers in the primary care setting.

BACKGROUND: Breast cancer chemoprevention can reduce breast cancer incidence in high-risk women; however, chemoprevention is underutilized in the primary care setting. We conducted a pilot study of decision support tools among high-risk women and their primary care providers (PCPs). METHODS: The intervention included a decision aid (DA) for high-risk women, RealRisks, and a provider-centered tool, Breast Cancer Risk Navigation (BNAV). Patients completed validated surveys at baseline, after RealRisks and after their PCP clinical encounter or at 6-months. Referral for high-risk consultation and chemoprevention uptake were assessed via the electronic health record. The primary endpoint was accuracy of breast cancer risk perception at 6-months. RESULTS: Among 40 evaluable high-risk women, median age was 64.5 years and median 5-year breast cancer risk was 2.19%. After exposure to RealRisks, patients demonstrated an improvement in accurate breast cancer risk perceptions (p = 0.02), an increase in chemoprevention knowledge (p < 0.01), and 24% expressed interest in taking chemoprevention. Three women had a high-risk referral, and no one initiated chemoprevention. Decisional conflict significantly increased from after exposure to RealRisks to after their clinical encounter or at 6-months (p < 0.01). Accurate breast cancer risk perceptions improved and was sustained at 6-months or after clinical encounters. We discuss the side effect profile of chemoprevention and the care pathway when RealRisks was introduced to understand why patients experienced increased decision conflict. CONCLUSION: Future interventions should carefully link the use of a DA more proximally to the clinical encounter, investigate timed measurements of decision conflict and improve risk communication, shared decision making, and chemoprevention education for PCPs. Additional work remains to better understand the impact of decision aids targeting both patients and providers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02954900 November 4, 2016 Retrospectively registered.

Real-world clinical outcomes with avelumab in patients with Merkel cell carcinoma treated in the USA: a multicenter chart review study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neuroendocrine neoplasm with annual incidence rates of 0.13-1.6 cases/100,000/year worldwide as of 2018. Chemotherapy for metastatic MCC (mMCC) has high objective response rates (ORRs), but responses are not durable and overall survival (OS) is poor. Avelumab (anti-programmed death-ligand 1) has demonstrated meaningful survival benefit and durable responses in clinical trials for mMCC. This study investigated real-world clinical outcomes in avelumab-treated patients with advanced (stage IIIB/IV) MCC in US academic medical centers. METHODS: We conducted a retrospective chart review of patients with advanced MCC who initiated avelumab between March 1, 2017, and July 31, 2019, at six US academic centers. Data were requested for eligible patients from index date through December 31, 2020. Descriptive analyses were conducted to assess demographic and clinical characteristics, real-world ORR (rwORR), real-world duration of response, real-world progression-free survival (rwPFS), and OS. RESULTS: Ninety patients with advanced MCC (82%, stage IV; 18%, stage IIIB) received avelumab. Median follow-up was 20.8 months (95% CI: 19.1 to 24.2). Median age was 68 years (range, 48-83), and the majority of patients were men (58%) and white (93%). The primary tumor was most commonly located on the lower limb (38%), with metastases mostly located in lymph nodes (68%), lung (52%), and viscera (52%). Approximately 42% and 26% of patients had an Eastern Cooperative Oncology Group performance status of 2 and 3, respectively. Seventy-three patients (81%) received avelumab as first-line treatment of advanced MCC, while 17 (19%) received avelumab as second-line or later treatment. The median duration of avelumab treatment was 13.5 months (95% CI: 6.4 to 30.6), with 42% of patients still receiving avelumab by the end of follow-up. Patients with avelumab treatment had an rwORR of 73% (95% CI: 64 to 83), median rwPFS of 24.4 months (95% CI: 8.31 to not estimable (NE)), and median OS of 30.7 months (95% CI: 11.2 to NE). CONCLUSIONS: This real-world study of patients with advanced MCC demonstrated that avelumab treatment resulted in a high response rate with durable responses and prolonged survival. The study findings validate the results demonstrated in prospective clinical trials and other observational studies.

Study protocol: Randomized controlled trial of web-based decision support tools for high-risk women and healthcare providers to increase breast cancer chemoprevention.

BACKGROUND: Chemoprevention using selective estrogen receptor modulators and aromatase inhibitors has been shown to reduce invasive breast cancer incidence in high-risk women. Despite this evidence, few high-risk women who are eligible for chemoprevention utilize it as a risk-reducing strategy. Reasons for low uptake include inadequate knowledge about chemoprevention among patients and healthcare providers, concerns about side effects, time constraints during the clinical encounter, and competing comorbidities. METHODS/DESIGN: We describe the study design of a randomized controlled trial examining the effect of two web-based decision support tools on chemoprevention decision antecedents and quality, referral for specialized counseling, and chemoprevention uptake among women at an increased risk for breast cancer. The trial is being conducted at a large, urban medical center. A total of 300 patients and 50 healthcare providers will be recruited and randomized to standard educational materials alone or in combination with the decision support tools. Patient reported outcomes will be assessed at baseline, one and six months after randomization, and after their clinic visit with their healthcare provider. DISCUSSION: We are conducting this trial to provide evidence on how best to support personalized breast cancer risk assessment and informed and shared decision-making for chemoprevention. We propose to integrate the decision support tools into clinical workflow, which can potentially expand quality decision-making and chemoprevention uptake. TRIAL REGISTRATION: NCT03069742.

An Applied Framework in Support of Shared Decision Making about BRCA Genetic Testing.

The United States Preventive Services Taskforce recommends that primary care providers screen patients for an increased risk of carrying a BRCA1 or BRCA2 mutation and refer those who meet family history criteria to genetic counseling. Such screening requires detailed and accurate family history data, which often goes uncollected during a primary care visit due to time constraints, competing priorities, and lack of awareness on behalf of both patients and providers. In order to address these barriers and promote appropriate genetic counseling referral, we developed a user-centered framework that collects and communicates relevant data in order to prepare patients and their primary care providers for an informed discussion on genetic counseling referral. This paper describes this framework and the underlining data schema that makes it possible.

Automatic Genetic Risk Assessment Calculation Using Breast Cancer Family History Data from the EHR compared to Self-Report.

Genetic testing is a method to assess hereditary cancer risk. However, it is under-utilized and various methods of family history intake have been evaluated in previous studies. The six-point-scale (SPS) is a validated family history screener that is used to determine eligibility for BRCA genetic counseling. We automated the calculation of the SPS score using structured family history data along with free text from the electronic health record (EHR) to detect detailed family history information of breast cancer. We extracted data for all women aged 35 to 74 who had screening mammography at Columbia University Medical Center (CUMC) from January 2015 to May 2017 (N=37,596). After we calculated SPS scores using structured and free-text EHR data, we compared the results with SPS score calculated from a baseline survey conducted for a prospective study called Know Your Risks: Assessment at Screening (KYRAS). Among 1,202 patients with EHR structured family history data, we found 1.43% had an SPS score of 6 higher which meets criteria for genetic counseling referral, while 12.05% of the survey respondents had SPS score of 6 or higher. Results show there is a need for more efficient methods to identify patients eligible for genetic counseling through EHR analysis.

Factors Associated with False Positive Results on Screening Mammography in a Population of Predominantly Hispanic Women.

Background: Potential harms of screening mammography include false positive results, such as recall breast imaging or biopsies.Methods: We recruited women undergoing screening mammography at Columbia University Medical Center in New York, New York. They completed a questionnaire on breast cancer risk factors and permitted access to their medical records. Breast cancer risk status was determined using the Gail model and a family history screener. High risk was defined as a 5-year invasive breast cancer risk of ≥1.67% or eligible for BRCA genetic testing. False positive results were defined as recall breast imaging (BIRADS score of 0, 3, 4, or 5) and/or biopsies that did not yield breast cancer.Results: From November 2014 to October 2015, 2,361 women were enrolled and 2,019 were evaluable, of whom 76% were Hispanic and 10% non-Hispanic white. Fewer Hispanic women met high-risk criteria for breast cancer than non-Hispanic whites (18.0% vs. 68.1%), but Hispanics more frequently engaged in annual screening (71.9% vs. 60.8%). Higher breast density (heterogeneously/extremely dense vs. mostly fat/scattered fibroglandular densities) and more frequent screening (annual vs. biennial) were significantly associated with false positive results [odds ratio (OR), 1.64; 95% confidence interval (CI), 1.32-2.04 and OR, 2.18; 95% CI, 1.70-2.80, respectively].Conclusions: We observed that women who screened more frequently or had higher breast density were at greater risk for false positive results. In addition, Hispanic women were screening more frequently despite having a lower risk of breast cancer compared with whites.Impact: Our results highlight the need for risk-stratified screening to potentially minimize the harms of screening mammography. Cancer Epidemiol Biomarkers Prev; 27(4); 446-53. ©2018 AACR.

Understanding Factors Associated with Uptake of BRCA1/2 Genetic Testing among Orthodox Jewish Women in the USA Using a Mixed-Methods Approach.

BACKGROUND/AIMS: Ashkenazi Jews have a 1:40 prevalence of BRCA1/2 mutations. Orthodox Jews are an understudied population with unique cultural and religious factors that may influence BRCA1/2 genetic testing uptake. METHODS: Using a mixed-methods approach, we conducted a cross-sectional survey and focus groups among Orthodox Jewish women in New York/New Jersey to explore factors affecting decision-making about BRCA1/2 genetic testing. RESULTS: Among 321 evaluable survey participants, the median age was 47 years (range, 25-82); 56% were Modern Orthodox and 44% Yeshivish/Chassidish/other; 84% were married; 7% had a personal history of breast or ovarian cancer. Nearly 20% of the women had undergone BRCA1/2genetic testing. Predictors of genetic testing uptake included being Modern Orthodox (odds ratio [OR] = 2.31), married (OR = 3.49), and having a personal or family history of breast or ovarian cancer (OR = 9.74). Focus group participants (n = 31) confirmed the importance of rabbinic consultation in medical decision-making and revealed that stigma was a prominent factor in decisions about BRCA1/2 testing due to its potential impact on marriageability. CONCLUSION: In order to increase the uptake of BRCA1/2 genetic testing among the Orthodox Jewish population, it is crucial to understand religious and cultural factors, such as stigma and effect on marriageability, and engage religious leaders in raising awareness within the community.

Chemoprevention Uptake among Women with Atypical Hyperplasia and Lobular and Ductal Carcinoma In Situ.

Women with atypical hyperplasia and lobular or ductal carcinoma in situ (LCIS/DCIS) are at increased risk of developing invasive breast cancer. Chemoprevention with selective estrogen receptor modulators or aromatase inhibitors can reduce breast cancer risk; however, uptake is estimated to be less than 15% in these populations. We sought to determine which factors are associated with chemoprevention uptake in a population of women with atypical hyperplasia, LCIS, and DCIS. Women diagnosed with atypical hyperplasia/LCIS/DCIS between 2007 and 2015 without a history of invasive breast cancer were identified (N = 1,719). A subset of women (n = 73) completed questionnaires on breast cancer and chemoprevention knowledge, risk perception, and behavioral intentions. Descriptive statistics were generated and univariate and multivariable log-binomial regression were used to estimate the association between sociodemographic and clinical factors and chemoprevention uptake. In our sample, 29.3% had atypical hyperplasia, 23.3% had LCIS, and 47.4% had DCIS; 29.4% used chemoprevention. Compared with women with atypical hyperplasia, LCIS [RR, 1.43; 95% confidence interval (CI), 1.16-1.76] and DCIS (RR, 1.54; 95% CI, 1.28-1.86) were significantly associated with chemoprevention uptake, as was medical oncology referral (RR, 5.79; 95% CI, 4.80-6.98). Younger women were less likely to take chemoprevention (RR, 0.61; 95% CI, 0.42-0.87), and there was a trend toward increased uptake in Hispanic compared with non-Hispanic white women. The survey data revealed a strong interest in learning about chemoprevention, but there were misperceptions in personal breast cancer risk and side effects of chemoprevention. Improving communication about breast cancer risk and chemoprevention may allow clinicians to facilitate informed decision-making about preventative therapy. Cancer Prev Res; 10(8); 434-41. ©2017 AACR.

Usability Testing of a Web-Based Decision Aid for Breast Cancer Risk Assessment Among Multi-Ethnic Women.

Chemoprevention with antiestrogens could decrease the incidence of invasive breast cancer but uptake has been low among high-risk women in the United States. We have designed a web-based patient-facing decision aid, called RealRisks, to inform high-risk women about the risks and benefits of chemoprevention and facilitate shared decision-making with their primary care provider. We conducted two rounds of usability testing to determine how subjects engaged with and understood the information in RealRisks. A total of 7 English-speaking and 4 Spanish-speaking subjects completed testing. Using surveys, think-aloud protocols, and subject recordings, we identified several themes relating to the usability of RealRisks, specifically in the content, ease of use, and navigability of the application. By conducting studies in two languages with a diverse multi-ethnic population, we were able to implement interface changes to make RealRisks accessible to users with varying health literacy and acculturation.