Conlin, Alison

Importance The NRG Oncology research organization and NSABP B-35 randomized clinical trial prospectively collected margin width data on postmenopausal women with hormone receptor (HR)–positive ductal carcinoma in situ (DCIS) who underwent lumpectomy, whole-breast irradiation (WBI), and randomly assigned adjuvant anastrozole or tamoxifen therapy. This permitted analysis of outcomes per margin width. Objective To analyze the effect of margin width on ipsilateral breast tumor recurrence (IBTR). Design, Setting, and Participants NSABP B-35 was a phase 3, double-blind, randomized clinical trial in which patients were randomized to either 5 years of tamoxifen or anastrozole. Postmenopausal women with HR-positive DCIS and tumor-free margins were eligible. Enrollment was from January 6, 2003, to June 15, 2006, in academic and community hospital members of the NSABP. Study data were analyzed from July 2024 to April 2025. Interventions There were no specific interventions based on lumpectomy margin width. Main Outcomes and Measures Lumpectomy margin width data were prospectively collected within 3 months of randomization. A pathology form classified margins as positive (ink on tumor), close (<1 mm), or negative (≥1 mm). For the negative margin subgroup, closest margin width was stated separately. Thus, an ancillary analysis using 1-mm and 2-mm margin width partitions was performed. Results A total of 3104 postmenopausal women (mean [SD] age, 61 [7.8] years) were enrolled in NSABP B-35. In an ancillary analysis, 2707 patients were included in the 1-mm margin width partition group, and 2546 patients were included in the 2-mm margin width partition group. IBTR was the most common first event, occurring in 90 of 2707 patients (3.3%): 24 of 502 patients (4.8%) with a margin width less than 1 mm and 66 of 2205 patients (3.0%) with a margin width greater than or equal to 1 mm. Ten-year unadjusted cumulative incidence of IBTR events was 5.6% vs 4.0% for margins less than 1 mm vs margins greater than or equal to 1 mm ( P = .04). Using 2 mm as the discriminant threshold for margin width, 39 of 879 patients (4.4%) with margins less than 2 mm and 49 of 1667 patients (2.9%) with margins greater than or equal to 2 mm experienced an IBTR first. Ten-year unadjusted cumulative incidence of IBTR events with margins less than or equal to 2 mm was 5.3% vs 3.8% for those with margins greater than 2 mm ( P = .05). In models adjusting for other patient and tumor factors, margin width was not a significant predictor of IBTR risk (2-mm threshold hazard ratio, 1.33; 95% CI, 0.86-2.06). Conclusions and Relevance Results of this ancillary analysis of the NSABP B-35 trial show that absolute differences in IBTR rates using margin width groupings of less than 1 mm or greater than or equal to 1 mm and margin width groupings of less than 2 mm or greater than or equal to 2 mm in postmenopausal women with HR-positive DCIS receiving lumpectomy, WBI, and adjuvant endocrine therapy were small. Omission of reexcision lumpectomies based on margin widths of less than 1 mm or less than 2 mm can be reconsidered in appropriate patients. Trial Registration ClinicalTrials.gov Identifier: NCT00053898

Abstract Background Breast cancer chemoprevention is underutilized among high-risk women. We examined whether decision support could increase informed decision making. Methods We conducted a cluster randomized controlled trial to evaluate the effect of a patient-facing decision aid (RealRisks) and provider tool (BNAV) compared with standard education on the number of women with high-risk breast lesions making informed choices. Questionnaires were administered at baseline and 6 and 12 months. The primary outcome was chemoprevention informed choice (defined as adequate knowledge and attitudes congruent with decision) at 6 months. Secondary endpoints included breast cancer risk perceptions, worry, chemoprevention knowledge, decision conflict, and chemoprevention decision. Results Across 31 randomized sites, we enrolled 210 providers, who were primarily breast health specialists. Of these, 24 sites (14 intervention, 10 control) enrolled 412 patients. Among 287 patients evaluable for the primary outcome, there were no statistically significant differences in informed choice between the intervention and control arms at 6 months (35% vs 27%, respectively; P = .20) and 12 months (37% vs 25%, respectively; P = .05). At 6 months, women in the intervention compared with control arm were more likely to have accurate breast cancer risk perceptions (31% vs 21%, respectively; P = .03) and adequate chemoprevention knowledge (33% vs 23%, respectively; P = .04). At 12 months, 52% of women in the control and 50% in the intervention arm self-reported initiating chemoprevention. Conclusion Decision support led to modest improvements in accurate risk perceptions and chemoprevention knowledge but not informed choice. Relatively high chemoprevention uptake was achieved among women with high-risk breast lesions managed mainly by breast health specialists. Trial Registration NCT04496739, https://clinicaltrials.gov/study/NCT04496739?cond=NCT04496739&viewType=Card&rank=1

Abstract Background: Breast cancer (BC) chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) remains underutilized among high-risk women. Improving knowledge about BC risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this BC risk reduction strategy. Methods: We conducted a cluster randomized controlled trial to evaluate the effectiveness of web-based patient and provider decision support, RealRisks and BNAV, to improve chemoprevention informed choice among women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS). Thirty-one sites, including academic and community practices across the U.S., were randomized to standard patient educational materials alone or combined with RealRisks and BNAV. A total of 412 patients and 210 healthcare providers were enrolled. Patient surveys were administered at baseline, 6 and 12 months. The primary outcome at 6 months was chemoprevention informed choice, defined as adequate chemoprevention knowledge and attitudes congruent with decision. Secondary endpoints included BC risk perceptions, worry, chemoprevention knowledge, decision conflict and chemoprevention decision. Assuming 10% loss to follow up (LTFU), roughly equal accrual across sites, and an intraclass coefficient (ICC) of 0.02, we had 90% power to detect a 15% absolute difference in informed choice if the event rate in the control arm was 10%. Results: Among 24 evaluable sites, 14 were randomized to the intervention arm and 10 to the control arm. Among 210 enrolled providers, median age was 46 (range, 28-83) and 78% were female; 75% physicians and 25% advanced practice providers/nurses; 53% medical oncologists, 29% surgeons, and 10% gynecologists/family practitioners/internists; and 83% had previously prescribed chemoprevention. Among 412 enrolled patients, median age was 53 (range, 35-74), including 77% White, 8% Black, and 10% Asian race, and 14% Hispanic ethnicity. In terms of BC risk factors, 77% had AH and 23% LCIS, 34% had a first-degree family history of BC, and 65% had heterogeneously or extremely dense breasts on mammography. Thirty percent were unevaluable for the primary endpoint (1% ineligible, 26% LTFU, 3% missing data). Among 288 evaluable patients (148 at intervention sites, 140 at control sites), the proportion of patients exercising informed choice at 6 months in the intervention and control arms was 35% vs. 27%, respectively (odds ratio [OR]=1.44, 95% confidence interval [CI]=0.84-2.46, p=0.19; observed ICC=0.006). Compared to patients in the control arm at 6 months, those in the intervention arm were more likely to have accurate BC risk perceptions (OR=1.80, 95% CI=1.11-2.91) and adequate chemoprevention knowledge (OR=1.62, 95% CI=1.00-2.61). We observed no significant differences in BC worry, decision conflict, or chemoprevention decision between study arms. At 6 months, 49% of women in the control arm and 51% in the intervention arm decided to take a SERM or AI for BC chemoprevention (p=0.58), a rate higher than anticipated. Conclusions: We did not observe a significant increase in informed choice among patients and providers assigned to chemoprevention decision support compared to standard educational materials alone. Among women with AH or LCIS seen mainly by breast specialists who prescribed chemoprevention, about half decided to take a SERM or AI. Therefore, relatively high chemoprevention uptake may be achieved among women with high-risk breast lesions managed by breast specialists. Chemoprevention decision support may improve decision antecedents, such as accurate BC risk perceptions and chemoprevention knowledge, but may have a limited role in changing health behaviors. Citation Format: K. D. Crew, G. L. Anderson, K. B. Arnold, A. Michel, M. T. DeLucie, C. W. Law, S. Pruthi, A. C. Sandoval Leon, R. Shirley, M. T. Grosse Perdekamp, S. V. Colonna, S. L. Krisher, T. King, L. D. Yee, T. J. Ballinger, C. Braun-Inglis, D. A. Mangino, K. B. Wisinski, C. A. DeYoung, M. Ross, J. D. Floyd, A. Kaster, L. VanderWalde, T. Saphner, C. Zarwan, S. Lo, C. Graham, A. K. Conlin, K. J. Yost, D. M. Agnese, C. Jernigan, D. L. Hershman, M. L. Neuhouser, J. A. Zell, B. Arun, R. Kukafka. Making informed choices on incorporating chemoprevention into care (MiCHOICE): Cluster randomized controlled trial of decision support for breast cancer chemoprevention, SWOG 1904 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-15.

Abstract Background: Despite evidence of substantial breast cancer risk reduction, few high-risk women adopt chemopreventive medications such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Women with benign breast disease, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have an increased risk of developing breast cancer and derive a greater benefit from antiestrogens compared to other high-risk women. Reasons for low uptake of chemoprevention include insufficient patient and clinician knowledge about antiestrogens, time constraints during the clinical encounter, and concerns about side effects. To address these barriers, we have developed patient and provider web-based decision support tools to improve informed choice about breast cancer chemoprevention among women with AH or LCIS. Study design: We are conducting a cluster-randomized controlled trial of clinical decision support to improve chemoprevention informed choice among women with AH or LCIS and their treating providers. Twenty-six U.S. sites through the SWOG Cancer Research Network were randomly assigned 1:1 to standard educational materials alone or in combination with the patient-centered decision aid (RealRisks) and provider decision support tool (BNAV). A total of 415 patients and 200 healthcare providers will be recruited from these sites. RealRisks consists of interactive modules to calculate personalized breast cancer risk and elicit preferences on chemoprevention. The modules are available in English and Spanish. BNAV is comprised of self-directed case-based learning modules on breast cancer risk assessment and chemoprevention. Patients complete questionnaires at baseline, 6 and 12 months. Providers complete surveys at baseline and after their enrolled patient’s 6-month clinical encounter. The primary endpoint is chemoprevention informed choice at 6 months, using a measure combining knowledge, attitude, and intention scales. Secondary endpoints include perceived breast cancer risk/worry, chemoprevention knowledge/intention, decision conflict/regret, shared decision-making, and chemoprevention uptake. For patients who begin chemoprevention, adherence and reasons for discontinuation are assessed annually for up to 5 years. Barriers and facilitators to implementing RealRisks and BNAV into clinic workflow will be assessed by conducting patient and provider interviews at baseline and mid-implementation. Eligibility criteria: Eligible patients include women, age 35-74 years, with AH or LCIS, no history of breast cancer, no prior use of SERMs or AIs, no bilateral mastectomies, English or Spanish-speaking, and access to the internet. Eligible providers include breast surgeons, medical oncologists, primary care providers, and physician extenders who see patients with AH or LCIS. Statistical methods: We have 90% power to detect a 15% increase in the frequency of chemoprevention informed choice with a 1-sided 0.025 level test, assuming an intraclass correlation (ICC) of 0.02 to account for clustering, roughly equal accrual at each site, 10% loss to follow-up, and ≤10% event rate in the control arm. Current/target accrual: The trial was activated on 9/1/2020. As of 7/7/2022, all 26 sites have been randomized, 157/200 providers and 184/415 patients have been enrolled. Discussion: Our hybrid effectiveness/implementation study seeks to evaluate the effectiveness of a multi-level intervention in promoting informed decision-making about breast cancer chemoprevention. Study results will provide valuable insights on how the decision support tools are integrated in diverse clinical settings. Citation Format: Katherine D. Crew, Garnet Anderson, Kathryn Arnold, Andrew Stieb, Jacquelyn N. Amenta, Cynthia Law, Ana Sandoval-Leon, Sarah Colonna, Tari King, Debra Mangino, Sandhya Pruthi, Maria Grosse Perdekamp, Christa Braun-Inglis, Stacy Krisher, Lisa Yee, Danielle Bertoni, Samantha Seaward, Kari B. Wisinski, Justin Floyd, Corrine Zarwan, Tarah J. Ballinger, Lindi VanderWalde, Masey M. Ross, Preston Steen, Shelly Lo, Alison Conlin, Kathleen Yost, John Ellerton, Erin Lin, Holly J. Pederson, Sagar Sardesai, Cheryl Jernigan, Dawn Hershman, Marian L. Neuhouser, Banu K. Arun, Rita Kukafka. SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-15-01.