Breast Cancer Screening Trials Research Articles

Receiving a pathogenic variant in a population breast cancer screening trial: a mixed method study

Receiving a pathogenic variant in a population breast cancer screening trial: a mixed method study

Expansion of outreach to native Hawaii and Pacific Islander communities to increase breast cancer screening and clinical trial awareness in underserved and rural Oahu.

e13725 Background: Multiple barriers exist in the enrollment of racial and ethnic minority groups into breast cancer screening and clinical trials. Such barriers include the lack of knowledge, mistrust, and access. To increase participation of rural-dwelling Native Hawaiian/Pacific Islanders (NHPI) and other underserved minority groups in breast cancer screening and clinical trials, a pilot project was developed to augment community engagement, provide education, and gain insights into the cancer screening/clinical trial process. Our objective was to engage rural Oahu's underserved communities in breast cancer screening and facilitate enrollment into the Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients of Breast Cancer Trial (TMIST) utilizing a team comprising of a cultural congruent and gender concordant Community Health Educator (CHE) and medical oncology health care provider. Methods: We reviewed the community activities over the course of a year. The CHE facilitated outreach by speaking at numerous church events and other community gatherings. Results: Participants did not respond favorably to surveys on social determinants of health. Common reasons for their reluctance included lack of perceived importance and medical mistrust. When discussing verbiage that was intimidating or confusing such as clinical trial protocol consent language, TMIST study participants conveyed a strong sense of dehumanization. Conclusions: A total of 93 women were screened for the TMIST clinical trial. Of those, 13 were enrolled in TMIST and 31 participants received mammograms. Participant insight highlighted the importance of education using culturally sensitive language and community engagement to combat the lack of knowledge and mistrust. Continued development of education materials centered around community involvement will improve the accrual of NHPI participation in breast cancer screening/clinical trials. We hope this project established a basis for equity in communities with low breast cancer screening and clinical trial participation rates. We intend to build upon the community partnerships forged during this pilot project.

Exploration and validation of optimal cut-off values for tPSA and fPSA/tPSA screening of prostate cancer at different ages

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (＜60, 60-＜70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.

Breast Cancer Screening and Treatment Clinical Trials Updated for 2023.

There are many active or recently completed breast cancer screening and treatment trials in 2023 that have the potential to fundamentally change the way breast radiologists practice medicine. Breast cancer screening trials may provide evidence to support supplemental screening beyond mammography to include US, contrast-enhanced mammography, and breast MRI. Furthermore, there are multiple efforts to support risk-adaptive screening strategies that would personalize screening modalities, frequencies, and ages of initiation. For breast cancer treatment, aims to reduce overtreatment may provide nonsurgical treatment options for women with low-risk breast cancer. Breast radiologists must be familiar with the study designs, major inclusion and exclusion criteria, and principal endpoints in order to determine when and how the study results should influence clinical care. As multidisciplinary team members, breast radiologists will have major roles in the success or failure of these trials as they transition from research to actual clinical practice.

Cohort profile: design and methods of the Chinese colorectal, breast, lung, liver, and stomach cancer screening trial (C-BLAST)

Cohort profile: design and methods of the Chinese colorectal, breast, lung, liver, and stomach cancer screening trial (C-BLAST)

The role of polygenic risk scores in breast cancer risk perception and decision-making.

Polygenic risk scores (PRS) have the potential to improve the accuracy of clinical risk assessments, yet questions about their clinical validity and readiness for clinical implementation persist. Understanding how individuals integrate and act on the information provided by PRS is critical for their effective integration into routine clinical care, yet few studies have examined how individuals respond to the receipt of polygenic risk information. We conducted an embedded Ethical, Legal, and Social Implications (ELSI) study to examine if and how unaffected participants in a US population breast cancer screening trial understood and utilized PRS, as part of a multifactorial risk score combining traditional risk factors with a genetic risk assessment, to make screening and risk-reduction decisions. Semi-structured qualitative interviews were conducted with 24 trial participants who were designated at elevated risk for breast cancer due to their combined risk score. Interviews were analyzed using a grounded theory approach. Participants understood PRS conceptually and accepted it as one of many risk factors to consider, yet the value and meaning they ascribed to this risk estimate varied. Most participants reported financial and insurance barriers to enhanced screening with MRI and were not interested in taking risk-reducing medications. These findings contribute to our understanding of how PRS may be best translated from research to clinical care. Furthermore, they illuminate ethical concerns about identifying risk and making recommendations based on polygenic risk in a population screening context where many may have trouble accessing appropriate care.

Test sensitivity in a prospective cancer screening program: A critique of a common proxy measure.

The true sensitivity of a cancer screening test, defined as the frequency with which the test returns a positive result if the cancer is present, is a key indicator of diagnostic performance. Given the challenges of directly assessing test sensitivity in a prospective screening program, proxy measures for true sensitivity are frequently reported. We call one such proxy empirical sensitivity, as it is given by the observed ratio of screen-detected cancers to the sum of screen-detected and interval cancers. In the setting of the canonical three-state Markov model for progression from preclinical onset to clinical diagnosis, we formulate a mathematical relationship for how empirical sensitivity varies with the screening interval and the mean preclinical sojourn time and identify conditions under which empirical sensitivity exceeds or falls short of true sensitivity. In particular, when the inter-screening interval is short relative to the mean sojourn time, empirical sensitivity tends to exceed true sensitivity, unless true sensitivity is high. The Breast Cancer Surveillance Consortium (BCSC) has reported an estimate of 0.87 for the empirical sensitivity of digital mammography. We show that this corresponds to a true sensitivity of 0.82 under a mean sojourn time of 3.6 years estimated based on breast cancer screening trials. However, the BCSC estimate of empirical sensitivity corresponds to even lower true sensitivity under more contemporary, longer estimates of mean sojourn time. Consistently applied nomenclature that distinguishes empirical sensitivity from true sensitivity is needed to ensure that published estimates of sensitivity from prospective screening studies are properly interpreted.

Correction to: Errors in Conduct of the CNBSS Trials of Breast Cancer Screening Observed by Research Personnel.

Correction to: Errors in Conduct of the CNBSS Trials of Breast Cancer Screening Observed by Research Personnel.

Surrogate endpoints in breast cancer screening trials – Authors' reply

We appreciate Ismail Jatoi's interest in the TOSYMA study. He challenges the choice of the primary endpoints—the invasive breast cancer detection rates at screening and the following invasive interval cancer rates—as used in this randomised controlled trial comparing digital breast tomosynthesis plus synthesised two-dimensional mammography with digital mammography.

“It’s personalized, but it’s still bucket based”: the promise of personalized medicine vs. the reality of genomic risk stratification in a breast cancer screening trial

Adaptive pragmatic clinical trials offer an innovative approach that integrates clinical care and research. Yet, blurring the boundaries between research and clinical care raises questions about how clinicians and investigators balance their patient care and research roles and what types of knowledge and risk assessment are most valued. This paper presents findings from an ethnographic ELSI (Ethical, Legal, Social Implications) study of an innovative clinical trial of risk-based breast cancer screening that utilizes genomics to stratify risk and recommend a breast cancer screening schedule commensurate with the assessed risk. We argue that the trial demonstrates a fundamental tension between the promissory ideals of personalized medicine, and the reality of implementing risk-stratified care on a population scale. We examine the development of a Screening Assignment Review Board in response to this tension which allows clinician-investigators to negotiate, but never fully resolve, the inherent contradiction of “precision population screening.”

Development and evaluation of a method for tumor growth simulation in virtual clinical trials of breast cancer screening.

Purpose: Image-based analysis of breast tumor growth rate may optimize breast cancer screening and diagnosis by suggesting optimal screening intervals and guide the clinical discussion regarding personalized screening based on tumor aggressiveness. Simulation-based virtual clinical trials (VCTs) can be used to evaluate and optimize medical imaging systems and design clinical trials. This study aimed to simulate tumor growth over multiple screening rounds. Approach: This study evaluates a preliminary method for simulating tumor growth. Clinical data on tumor volume doubling time (TVDT) was used to fit a probability distribution ("clinical fit") of TVDTs. Simulated tumors with TVDTs sampled from the clinical fit were inserted into 30 virtual breasts ("simulated cohort") and used to simulate mammograms. Based on the TVDT, two successive screening rounds were simulated for each virtual breast. TVDTs from clinical and simulated mammograms were compared. Tumor sizes in the simulated mammograms were measured by a radiologist in three repeated sessions to estimate TVDT. Results: The mean TVDT was 297days (standard deviation, SD, 169days) in the clinical fit and 322days (SD, 217days) in the simulated cohort. The mean estimated TVDT was 340days (SD, 287days). No significant difference was found between the estimated TVDTs from simulated mammograms and clinical TVDT values ( ). No significant difference ( ) was observed in the reproducibility of the tumor size measurements between the two screening rounds. Conclusions: The proposed method for tumor growth simulation has demonstrated close agreement with clinical results, supporting potential use in VCTs of temporal breast imaging.

A multilevel intervention increased accrual of Native Hawaiians and other Pacific Islanders to a national breast cancer screening trial.

6547 Background: The University of Hawaii Cancer Center (UHCC) Minority/Underserved NCI Community Oncology Research Program (Hawaii MU NCORP) provides access to NCI-sponsored clinical trials in Hawaii. The Hawaii MU NCORP is dedicated to increasing minority and underserved accruals to clinical trials. Native Hawaiian women have the highest breast cancer incidence and mortality; only 26% of Micronesian women in Hawaii over the age of 40 have ever had a mammogram. In 2018, the Hawaii MU NCORP became a recruitment site for the ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST). A pilot study was launched in 2019, to support our NCORP recruitment of underrepresented Native Hawaiian and other Pacific Islander (NHPI) women to the TMIST study. Subsequently, specific funding was provided by the NCI’s Center to Reduce Cancer Health Disparities that enabled the UHCC’s Office of Community Outreach and Engagement (COE) to develop an effective multilevel recruitment strategy together with the Hawaii MIU NCORP. Methods: To foster community awareness of the TMIST study among NHPI women, the UHCC COE hired a Community Health Educator (CHE). The CHE, a Pacific Islander woman, utilized small group educational sessions to provide culturally and linguistically appropriate cancer prevention information and promote the TMIST study to NHPI women in Hawaii. The CHE worked in partnership with Hawaii MU NCORP clinical research associates (CRAs) in these efforts. In 2020, statewide COVID-19 health and safety protocols were enacted, limiting public group interactions in Hawaii. Despite this challenge, the CHE successfully adapted the in-person educational sessions on clinical trials and TMIST to conduct sessions using Zoom and Facebook Messenger. Results: Before the hire of the CHE in 2019, only one Pacific Islander (Micronesian) woman was recruited to the TMIST in Hawaii. The CHE conducted 21 community health events with 426 attendees from 2019 to 2021. The Hawaii MU NCORP NHPI TMIST enrollment went from the 9.9% in 2018 to 2019, to 20.1% in 2019 to 2020 and to 33% in 2020 to 2021. To date, 18 Micronesian, 52 Native Hawaiian and 6 Other Pacific Islander women out of 353 participants ware enrolled. Conclusions: The multilevel intervention of our CHE, in collaboration with NCORP staff providing clinical trial awareness training and community outreach, resulted in increasing the enrollment of NHPI women to the TMIST Trial. CHE-led community health education sessions on cancer prevention can be delivered using emergent technologies and social media. The use of culturally and gender concordant CHEs working with CRAs have the potential to increase awareness and accruals to cancer clinical trials.

Errors in Conduct of the CNBSS Trials of Breast Cancer Screening Observed by Research Personnel.

To investigate why the Canadian National Breast Screening Study (CNBSS) did not show mortality reduction with mammography. This study explored long-standing concerns related to the validity of the randomization process, methods of recruiting women to participate in the trials, and training of the staff working in the CNBSS. Surviving former CNBSS personnel, whose roles involved direct recruitment, enrollment, randomization, clinical examination, image interpretation, and management of patients in the CNBSS were interviewed. Individuals were contacted and consented to provide firsthand accounts of daily operations and adherence to research protocols via standardized questions. Consistency of observational data with quantitative results from the CNBSS trials was evaluated. Eleven of 28 (39.3%) staff confirmed that women with preexisting symptoms of breast cancer were systematically recruited at some centers; 57.1% (16/28) confirmed that personnel performing screening in CNBSS had very limited training and experience; 39.3% (11/28) verified that imaging equipment was often substandard; 50% (14/28) indicated that mammography image quality was generally poor; and 28.6% (8/28) corroborated that in some cases surgeons were unwilling to perform biopsies or surgeries for women with suspicious abnormalities found only on screening mammography that lacked a palpable correlate. These firsthand accounts provide new information confirming that the CNBSS did not consistently and rigorously assess the true efficacy of screening mammography. The staff accounts clarify reasons why the CNBSS results were outliers compared with the six other randomized trials of screening mammography and should not be used as credible scientific evidence to inform health policy.

Abstract P5-19-01: The impact of streamlined processes and patient-directed messaging to improve enrollment in a remote, pragmatic clinical trial

Abstract Background Recent advances in technology have made it possible to conduct remote clinical trials that allow individuals to participate from home with comfort, privacy, and ease. Despite these advances, challenges persist in running remote trials, such as survey question redundancies, lack of patient-initiated data-sharing tools, and unclear patient communication around critical enrollment steps. The Women Informed to Screen Depending on Measures of risk (WISDOM) Study is a pragmatic, preference-tolerant randomized control breast cancer screening trial comparing personalized risk-based screening to traditional, annual screening. The study population includes women ages 40-74 without a history of breast cancer or DCIS. Since 2016, study enrollment has been available to all women in the U.S. who meet study eligibility criteria. Since October 2020, WISDOM has implemented multiple strategies to improve participant experience: participant-initiated data-sharing tools and clear participant messaging. This abstract presents the efficacy of these interventions as they relate to increasing patient enrollment in remote, pragmatic clinical trials. Methods The WISDOM Study online enrollment process includes registration, participant study arm selection or randomization, online consent, and enrollment (submission of multiple study surveys over a secure, online platform). Barriers to online enrollment were uncovered through an internally-conducted needs assessment of participants who enrolled between 2019-2020, and participant feedback obtained through phone interviews conducted by WISDOM’s embedded ethics study. Improvements to our online enrollment procedures were executed in October 2020 and included: improving the clarity of study arm selection options, streamlining data collection surveys, and enacting a secure, patient-initiated online data-sharing tool and an online portal feature with auto-launch of critical information. Study metrics were obtained through Google Analytics and Salesforce. Results Prior to the end of 2020, only 62% of the 30,046 participants who registered for the WISDOM Study completed study enrollment. After improving the enrollment process, of the 5,334 participants registered for the study between Jan-June 2021, 69% completed the enrollment process finishing both the online consent and survey forms. Conversion from consent to enrollment went from 78% in January 2020 to 93% in June 2021. Currently, 56% participants complete enrollment in one day. Streamlining online patient questionnaires led to an increase in completion rates, with 75% of participants completing their yearly surveys, compared to 59% prior to April 2021. A secure patient upload feature for data sharing led to 1,054 participants successfully sharing their mammogram reports with WISDOM between March - June 2021. Previously, mammogram reports were missing for 20% of enrolled participants. This feature has enabled WISDOM to process 300 additional mammogram reports per month. Integration of an auto-launch feature in the participant’s portal in Feb 2021 has led to a 17% increase in participants viewing their screening recommendations in Yr 1. Prior to auto-launch, only 59% (n=6328) of Yr 1 screening recommendations and 61% (n=3681) of genetic testing reports were viewed by participants. Since implementation, the numbers increased to 78% (n=8406) and 85% (n=5160), respectively. Conclusions. Streamlining data to the most essential elements, and minimizing the steps required to share clinical documents, complete questionnaires and open key study notification is essential to improving enrollment rates in virtual, pragmatic trials. Patient-initiated data-sharing tools such as the ability for participants to share documents through secure, online portals is one example of success. Citation Format: Patricia Choy, Tomiyuri Lewis, Stephanie Flores, Leah Sabacan, Halle Thannickal, Steffanie Goodman, Yiwey Shieh, Lisa Madlensky, Jeffrey A. Tice, Elad Ziv, Martin Eklund, Amie Blanco, Barry Tong, Deborah Goodman, Nancy Anderson, Heather Harvey, Steele Fors, Hannah Lui Park, Antonia Petruse, Skye Stewart, Samrrah Raouf, Janet Wernisch, Barbara Koenig, Celia Kaplan, Robert Hiatt, Neil Wenger, Vivian Lee, Diane Heditsian, Susie Brain, Dolores Moorehead, Barbara A Parker, Alexander Borowsky, Hoda Anton-Culver, Arash Naeim, Andrea Kaster, Laura van 't Veer, Andrea Z LaCroix, Olufunmilayo I. Olopade, Deepa Sheth, Agustin Garcia, Rachel Lancaster, Jennifer James, Galen Joseph, Wisdom Study, Athena Breast Health Network Investigators and Advocates, Allison Stover Fiscallini, Laura Esserman. The impact of streamlined processes and patient-directed messaging to improve enrollment in a remote, pragmatic clinical trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-19-01.

The limits of personalization in precision medicine: Polygenic risk scores and racial categorization in a precision breast cancer screening trial.

Population-based genomic screening is at the forefront of a new approach to disease prevention. Yet the lack of diversity in genome wide association studies and ongoing debates about the appropriate use of racial and ethnic categories in genomics raise key questions about the translation of genomic knowledge into clinical practice. This article reports on an ethnographic study of a large pragmatic clinical trial of breast cancer screening called WISDOM (Women Informed to Screen Depending On Measures of Risk). Our ethnography illuminates the challenges of using race or ethnicity as a risk factor in the implementation of precision breast cancer risk assessment. Our analysis provides critical insights into how categories of race, ethnicity and ancestry are being deployed in the production of genomic knowledge and medical practice, and key challenges in the development and implementation of novel Polygenic Risk Scores in the research and clinical applications of this emerging science. Specifically, we show how the conflation of social and biological categories of difference can influence risk prediction for individuals who exist at the boundaries of these categories, affecting the perceptions and practices of scientists, clinicians, and research participants themselves. Our research highlights the potential harms of practicing genomic medicine using under-theorized and ambiguous categories of race, ethnicity, and ancestry, particularly in an adaptive, pragmatic trial where research findings are applied in the clinic as they emerge. We contribute to the expanding literature on categories of difference in post-genomic science by closely examining the implementation of a large breast cancer screening study that aims to personalize breast cancer risk using both common and rare genomic markers.

Breast Cancer Screening Trials: Endpoints and Overdiagnosis.

Screening mammography was assessed in 9 randomized trials initiated between 1963 and 1990, with breast cancer-specific mortality as the primary endpoint. In contrast, breast cancer detection has been the primary endpoint in most screening trials initiated during the past decade. These trials have evaluated digital breast tomosynthesis, magnetic resonance imaging, and ultrasound, and novel screening strategies have been recommended solely on the basis of improvements in breast cancer detection rates. Yet, the assumption that increases in tumor detection produce reductions in cancer mortality has not been validated, and tumor-detection endpoints may exacerbate the problem of overdiagnosis. Indeed, the detection of greater numbers of early stage breast cancers in the absence of a subsequent decline in rates of metastatic cancers and cancer-related mortality is the hallmark of overdiagnosis. There is now evidence to suggest that both ductal carcinoma in situ and invasive cancers are overdiagnosed as a consequence of screening. For each patient who is overdiagnosed with breast cancer, the adverse consequences include unnecessary anxiety, financial hardships, and a small risk of morbidity and mortality from unnecessary treatments. Moreover, the overtreatment of breast cancer, as a consequence of overdiagnosis, is costly and contributes to waste in health-care spending. In this article, we argue that there is a need to establish better endpoints in breast cancer screening trials, including quality of life and composite endpoints. Tumor-detection endpoints should be abandoned, because they may lead to the implementation of screening strategies that increase the risk of overdiagnosis.

All-cause mortality versus cancer-specific mortality as outcome in cancer screening trials: A review and modeling study.

BackgroundAll‐cause mortality has been suggested as an end‐point in cancer screening trials in order to avoid biases in attributing the cause of death. The aim of this study was to investigate which sample size and follow‐up is needed to find a significant reduction in all‐cause mortality.MethodsA literature review was conducted to identify previous studies that modeled the effect of screening on all‐cause mortality. Microsimulation modeling was used to simulate breast cancer, lung cancer, and colorectal cancer screening trials. Model outputs were: cancer‐specific deaths, all‐cause deaths, and life‐years gained per year of follow‐up.ResultsThere were large differences between the evaluated cancers. For lung cancer, when 40 000 high‐risk people are randomized to each arm, a significant reduction in all‐cause mortality could be expected between 11 and 13 years of follow‐up. For breast cancer, a significant reduction could be found between 16 and 26 years of follow‐up for a sample size of over 300 000 women in each arm. For colorectal cancer, 600 000 persons in each arm were required to be followed for 15‐20 years. Our systematic literature review identified seven papers, which showed highly similar results to our estimates.ConclusionCancer screening trials are able to demonstrate a significant reduction in all‐cause mortality due to screening, but require very large sample sizes. Depending on the cancer, 40 000‐600 000 participants per arm are needed to demonstrate a significant reduction. The reduction in all‐cause mortality can only be detected between specific years of follow‐up, more limited than the timeframe to detect a reduction in cancer‐specific mortality.

Identification of the Fraction of Indolent Tumors and Associated Overdiagnosis in Breast Cancer Screening Trials.

It is generally accepted that some screen-detected breast cancers are overdiagnosed and would not progress to symptomatic cancer if left untreated. However, precise estimates of the fraction of nonprogressive cancers remain elusive. In recognition of the weaknesses of overdiagnosis estimation methods based on excess incidence, there is a need for model-based approaches that accommodate nonprogressive lesions. Here, we present an in-depth analysis of a generalized model of breast cancer natural history that allows for a mixture of progressive and indolent lesions. We provide a formal proof of global structural identifiability of the model and use simulation to identify conditions that allow for parameter estimates that are sufficiently precise and practically actionable. We show that clinical follow-up after the last screening can play a critical role in ensuring adequately precise identification of the fraction of indolent cancers in a stop-screen trial design, and we demonstrate that model misspecification can lead to substantially biased estimates of mean sojourn time. Finally, we illustrate our findings using the example of Canadian National Breast Screening Study 2 (1980-1985) and show that the fraction of indolent cancers is not precisely identifiable. Our findings provide the foundation for extended models that account for both in situ and invasive lesions.

Abstract OT3-03-01: Preference-Tolerant randomized trial of risk-based vs. annual breast cancer screening: WISDOM study in progress

Abstract Purpose: Women Informed to Screen Depending on Measures of risk (WISDOM) trial is a pragmatic study comparing two real world approaches to clinical care for breast screening: annual screening versus personalized screening. The novelty of the personalized arm of the study is that we are combining known risk factors (age, family history, history of breast disease, ethnicity, BIRADS breast density, and genetics) into a single risk assessment model. All components of the model have been tested and established, but have never been used jointly. The goal of the WISDOM study is to examine the effectiveness of personalized breast cancer screening and to bring objective recommendations to the current mammography screening debate. Methods: The WISDOM trial will enroll 100,000 women with a preference-tolerant design that will determine if risk-based screening vs. annual screening, is as safe, less morbid, enables prevention, and is preferred by women. Women 40 - 74 years of age with no history of breast cancer or DCIS, and no previous double mastectomy can join the study from the WISDOM Study website (wisdomstudy.org). All participants sign up, elect randomization or self-select the study arm, provide electronic consent using DocuSign (eConsent), and sign a Medical Release Form. For all participants, 5-year risk of developing breast cancer is calculated according to the Breast Cancer Screening Consortium (BCSC) model. For participants in the personalized arm, the overall 5-year risk BCSC score is combined with a Polygenic Risk Score, based on a genetic test including mutations in 9 genes (BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, ATM, PALB2, and CHEK2) and a panel of 75 common single nucleotide polymorphisms known to increase breast cancer risk. Risk stratification will determine frequency of screening. The study is registered on ClinicalTrials.gov as NCT02620852. Results: As of June 12th 2017, the WISDOM study is live at all UC medical centers and recruitment is open to all eligible women in California. Up to date 4,769 eligible women registered at all sites. 2,823 women have consented in the trial. 64% were randomized and 36% chose their screening arm. A pilot was conducted to test the logistics of online participation and examine the acceptance of the study design and approach. We are partnering with health insurance companies and self-insured companies to reach our recruitment goal. Conclusions: Enrollment will be completed by end of 2018. Acknowledgment: support by the Patient-Centered Outcomes Research Institute (PCORI), PCS-1402-10749 to L.J.E. (*) Authors equally contributed to this work. Citation Format: Acerbi I, Abihider K, Ling J, Layton T, DeRosa D, Madlensky L, Tice J, Shieh Y, Ziv E, Sarrafan S, Firouzian R, Tong B, Blanco A, Lee V, Heditsian D, Brain S, Kaplan C, Borowsky A, Anton-Culver H, Naeim A, Cink T, Stover Fiscalini A, Parker B, van 't Veer L, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, LaCroix A, Esserman L. Preference-Tolerant randomized trial of risk-based vs. annual breast cancer screening: WISDOM study in progress [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-03-01.

Abstract PD2-14: Participation in a personalized breast cancer screening trial does not increase anxiety at baseline

Abstract Introduction: The purpose of this study is to examine whether participation in a personalized screening trial is associated with anxiety or breast cancer worry. The Patient Centered Outcomes Research Institute recently funded WISDOM (Women Informed to Screen Depending On Measures of risk), which is a randomized trial that tests the safety and efficacy of basing starting age, stopping age, frequency and modality of breast cancer screening on individual risk (Clinical Trials Identifier NCT02620852). Methods: In WISDOM, participants can be randomized to annual screening or personalized screening arm, or self-select an arm an observational cohort. This interim analysis examined the first 1817 participants to determine if the personalized risk arm is acceptable and to explore whether baseline anxiety was associated with study arm. For acceptability our target was to have &amp;gt;60% of participants agree to randomization. Participants completed questions about their Risk Perception, the PROMIS Anxiety short form 8a (total scores 8-40 with higher scores indicating more anxiety), and Breast Cancer Risk Worry (BCRW) survey (total scores 5-20) with higher scores indicating more worry) at baseline and before they were given information on their personal risk or study assignment. For the purposes of these analyses, we defined high anxiety to be the percentage of participants scoring =&amp;gt;22 on the PROMIS and &amp;gt;8 on the BCRW. Results: The participants were recruited from three sites (UCSD, UCSF, Sanford Health). Of the 1817 initial participants, 1643 completed the baseline questionnaire. Participants has a mean age of 57 years (SD 9). 15.8% felt their chances of developing breast cancer was high, 19.5% felt their chance of developing breast cancer was greater than the average women, and 56.6% felt their lifetime risk of developing breast cancer was &amp;gt;25. Risk perception was not significantly different between women who opted to be randomized versus the observational arm. The majority of participants were willing to be randomly assigned to an arm (1071/1643, 65.1%). Of those who joined the observational cohort, the majority selected personalized risk arm (474/572, 82.9%). Overall, PROMIS anxiety scores were low at baseline (14.0 MEAN (SD 4.6)) as were the Breast Cancer Risk Worry scores (5.7 MEAN (SD 1.05)). Less than 8% of participants had PROMIS scores &amp;gt;22 and that did not vary across the randomized or observational groups (P=0.2)). About 2% of participants had a BCRW scores &amp;gt;8. Women who worried with breast cancer were more likely to select to be in the observational (3.5%) than randomized (1.7%) arm of the study (P=0.02). Conclusions: For the women approached to participate in Wisdom, personalized screening was acceptable alternative to annual mammography. Participants in general overestimated their lifetime risk of breast cancer, had very low anxiety and low breast cancer worry. Those who were worried about breast cancer opted more often for the observational arm of the study to allow them to choose between the personalized versus annual arm. Future analyses will follow participants prospectively to determine adherence to assigned or selected arm, and whether anxiety changes after receipt of their personalized risk information. Citation Format: Naeim A, Sepucha K, Wenger N, Eklund M, Annette S, Madlensky L, van't Veer L, Parker B, Yau C, Cink T, Anton-Culver H, Borowsky A, Petruse A, Sarrafan S, Stover-Fiscalini A, LaCroix A, Adduci K, Wisdom Advocate Partners, Laura E. Participation in a personalized breast cancer screening trial does not increase anxiety at baseline [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-14.