McGuire, Kandace P.

Abstract Objective To test the effectiveness of a surgical web‐based decision aid (DA) in improving knowledge. Summary of Background Data DAs support decision making by providing information about the options. Methods A stepped wedge trial was conducted in 10 National Cancer Institute Community Oncology Research Program clinics (Alliance for Clinical Trials in Oncology). Clinics were randomized to time of transition from usual care (UC) to delivery of a web‐based DA. Patients with stage 0 through 3 breast cancer being considered for surgery were enrolled. Knowledge (primary outcome) was measured using the Breast Cancer Surgery Decision Quality Instrument and patients were asked, “How informed do you feel?” Intervention effects were tested with linear mixed‐effects models, accounting for surgeon and clinic‐level clustering, time, and enrollment after COVID. Additional models controlled for demographics. Results A total of 44% of DA arm patients reviewed the DA and 58% in UC arm reported reviewing “any information.” Being in the DA arm versus UC was not associated with knowledge. However, “review of information” was associated with higher knowledge. In addition, non‐White race and lower education were associated with lower knowledge. The DA arm was associated with higher perceptions of feeling informed (parameter estimate 1.36; 95% CI, 0.18–2.55; p = .02); this persisted even when controlling for review of information or demographics. Conclusion Improved knowledge was not demonstrate with a web‐based DA versus UC. Interestingly, the DA was associated with a higher likelihood of feeling informed. Future research will explore the discrepancy between patients feeling informed but having low knowledge, especially for disadvantaged patients. Trial Registration ClinicalTrials.gov Identifier: NCT0376600

314 Background: In a recent trial, we observed no statistically significant increase in engagement after a web-based decision aid (DA) was delivered to breast cancer patients prior to a surgical consult. However, a minority of the intervention group (44%) reviewed the DA. The objective is to assess the effect of the DA on engagement for the cohort of patients who reviewed it. Methods: A stepped wedge trial was conducted with 10 NCI Community Oncology Research Program clinics that care for a high proportion of socioeconomically disadvantaged patients (6/2019-12/2021). Clinics were randomized to time of transition from usual care (UC) to delivery of a DA. Patients with stage 0-3 breast cancer eligible for surgery provided consent prior to a surgical consult. Engagement was measured from audio-recorded surgical consults (Active Patient Behaviors, Street protocol). For this analysis, we identified a cohort of treatment compliant (TC) patients who reviewed the DA. Intervention effects comparing TC and UC groups were tested with linear mixed-effects models, accounting for time, enrollment post-COVID, and patient age, race, education, and socioeconomic disadvantage (assessed with Area Deprivation Index and dichotomized). Exploratory models were generated using Active Patient Behavior subcomponents (asking questions, assertive responses, expressions of concern) as the outcome. Results: The cohort includes 407 patients (UC 264; TC 143). TC patients were more likely to be white (TC 73%, UC 64%, p=0.03), have a college degree (TC 65%, UC 55%, p=0.05), and not be disadvantaged (TC 89%, UC 72%, p=0.001). TC was associated with increased engagement (8.2 [0.08, 16.2], p=0.048, Table). A college degree was associated with higher, while black race and socioeconomic disadvantage lower, engagement. On exploratory analyses, TC had a stronger association with higher levels of assertive responses (2.9 [-0.3, 6.1], p=0.07) compared with asking questions (5.2 [-1.4, 11.9], p=0.12) or expressions of concern (0.08 [-0.60, 0.76], p=0.82). Conclusions: We observed increased engagement in breast cancer patients who reviewed a DA prior to a surgical consult. However, we also observed differences based on race, education, and socioeconomic disadvantage. Further research will identify adjunct interventions to combine with the DA to improve cancer care delivery for diverse populations. Support: UG1 CA189823; AHRQ R01HS025194; https://acknowledgments.alliancefound.org. Clinical trial information: NCT03766009 .[Table: see text]

6520 Background: Increased patient engagement in decision making may mitigate disparities in breast cancer surgical care. Socioeconomically disadvantaged patients disproportionately experience barriers to engagement. Decision aids (DA) increase engagement by providing information, establishing role expectations during the consult, and increasing confidence in surgeon interactions. The objective was to test the effectiveness of a surgical web-based DA in increasing engagement among breast cancer patients in clinics that care for a high proportion of socioeconomically disadvantaged patients. Methods: A stepped wedge trial was conducted with 10 NCI Community Oncology Research Program clinics (Alliance for Clinical Trials in Oncology Research Base, 6/19-12/21). Clinics were randomized to time of transition from usual care (UC) to delivery of a web-based DA. Patients with stage 0-3 breast cancer eligible for surgery provided consent prior to a surgical consult. Socioeconomic disadvantage was assessed with the Area Deprivation Index measured at the zip+4 level and dichotomized. Patient engagement was measured by Patient’s Self-Efficacy in Patient-Physician Interactions (PEPPI-5, follow-up survey) and count of Active Patient Behaviors (Street protocol, audio recorded consult). Intervention effects were tested with linear mixed-effects models, accounting for surgeon and clinic-level clustering, time, and enrollment post-COVID. Heterogeneity of treatment effect by socioeconomic disadvantage was assessed with an interaction term. Results: 573 patients enrolled. 44% (136/309) reviewed the DA. No significant difference in engagement was observed comparing DA and UC for PEPPI-5 (-0.80 [95% CI -2.13, 0.54], p = 0.24) or Active Patient Behaviors (2.52 [CI -4.11, 9.15], p = 0.46). Enrollment post-COVID was associated with increased Active Patient Behaviors (9.59 [CI 1.76, 17.43], p = 0.02) but no change in PEPPI-5 (-1.31 [CI -2.88, 0.26], p = 0.10). No heterogeneity of treatment effect was observed. Conclusions: In this trial conducted in clinics that serve diverse populations, no significant relationship was observed between a web-based DA and patient engagement. Conducting this stepped wedge trial during the pandemic was challenging. Future analyses will explore the impact of COVID on outcomes and effect of the decision aid for patients who reviewed it. UG1 CA189823; AHRQ R01HS025194; https://acknowledgments.alliancefound.org . Clinical trial information: NCT03766009 . [Table: see text]

507 Background: The 21-gene Recurrence Score (OncotypeDX Breast Cancer Assay) predicts outcome and benefit from chemotherapy (CT) in early stage ER+ BC treated with adjuvant endocrine therapy. We evaluated the association between Recurrence Score (RS), time to progression (TTP), and overall survival (OS) in patients with stage IV BC enrolled in TBCRC 013. Methods: TBCRC 013 is a registry study evaluating surgery of the primary tumor in pts presenting with Stage IV BC. From 7/09 - 4/12, 128 evaluable pts were enrolled in two cohorts (A: metastases (mets) with intact primary tumor (n=112); B: mets within 3 months of primary surgery (n=16)). This study includes 110 pts with pre-treatment primary tumor samples available for analysis. Clinical variables, TTP and OS were correlated with RS using long-rank, Kaplan-Meier and Cox regression. Results: Median pt age was 52yrs (21-79) and median tumor size 3.1cm (0.7-15). 82 (80%) were ER+, 83 (81%) Her2(-) and 51 (46%) had bone-only mets. Cohorts A and B did not differ. At a median follow-up of 26 mos (1-47), median TTP is 19 mos (95%CI16-25) and surgery is not associated with OS. 102 samples qualified for RS. 23 (23%) had low RS<18, 29 (28%) intermediate RS, 18-30; and 50 (49%) high RS≥31. Age, tumor size or site of 1stmets was not associated with RS. Risk groups were prognostic for TTP in ER+ pts and for 2 yr OS in ER+Her2- pts (Table). In Cox models continuous RS was also prognostic for TTP in ER+ pts (HR 3.5; for 50 point difference (PD) 95%CI 1.5-8.1, p=0.003) and for OS in ER+Her2- pts (HR 21.4, for 50 PD 95%CI 2.2-204.4, p=0.008). In MVA, adjusting for clinical variables, RS remained prognostic for TTP in ER+ pts (p=0.01). Further analysis of surgery in this trial is ongoing. Conclusions: The 21-gene RS is independently prognostic for TTP in ER+ Stage IV BC. RS is also prognostic for OS in ER+Her2- BC, suggesting that a high RS may be a surrogate for endocrine resistance and could be used to select pts with ER+ Stage IV BC for CT. A randomized trial to address this hypothesis is warranted. Clinical trial information: NCT00941759. [Table: see text]

Abstract Background- The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. Studies of cell-free DNA in the peripheral blood of breast cancer patients suggest that methylated DNA markers in serum or plasma could be used for detection of advanced disease, monitoring of therapeutic response, and for early detection of disease recurrence. Methods- A genome-wide serum DNA methylome array (Illumina HumanMethylation27 BeadChip) analysis was conducted on cell-free circulating DNA in serum from women with stage IV recurrent breast cancer, and 232 key CpG loci were identified. Methylation for this panel of 10 gene loci was evaluated using our newly developed cMethDNA assay to detect miniscule amounts of methylated DNA in Training and Test sets of sera from a total of 112 women (n = 55 normal, n = 57 metastatic breast cancer). The clinical sensitivity and specificity of the assay, along with technical reproducibility, was determined. To evaluate the concordance of DNA methylation patterns, the 10 gene panel was tested on 22 DNA sets of primary tumor, metastases and serum from the same patient. Finally, the ability of cMethDNA to monitor response to therapy was evaluated in 28 patients with metastatic disease. Results- A normal laboratory threshold of 7 cumulative methylation units was set and assay parameters were locked, based on Receiver Operating Characteristic (ROC) analyses of DNA from 300 ul of patient sera in the Training set (normal, n = 28; cancer, n = 24; 92% sensitivity, 96% specificity, and AUC = 0.950). Evaluation of the Test set of patient sera (normal, n = 27; cancer n = 33) resulted in detection of metastatic breast cancer with 91% sensitivity, 100% specificity, and AUC = 0.994 (0.984-1.005, p&lt;0.0001). Reproducibility of the cMethDNA assay increased with copy number; with the highest variation at 50 copies (CV = 29.1%) and the lowest at 3,200 copies (CV = 2.5%) of methylated DNA. The test was shown to be operator independent (ICC = 0.99). Evaluation of concordance between primary and disseminated tumor methylation showed that the methylation pattern from any given individual is highly conserved between serum, primary tissue and their metastases, and poorly conserved between different individuals. cMethDNA analysis of 28 patients before and after initiation of therapy showed a decrease in cumulative methylation in women with stable/responsive disease and a correlation with disease progression free survival (p&lt;0.0001). Conclusion- Together, our data suggest that the cMethDNA test 1) can detect tumor DNA shed into blood, 2) reflect the methylation alterations typical of the primary tumor and its metastatic lesions, and 3) reflect response to treatment after chemotherapy. Next, we will test the clinical utility of cMethDNA in independent clinical trial sample sets where it's complementary and independent roles will be examined against CA15.3 and CTC assays. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-06-01.

Abstract The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. We developed cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers identified by mining our previously reported study of DNA methylation patterns in breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip) and then validating the 10-gene panel in The Cancer Genome Atlas project breast cancer methylome database. For cMethDNA, a fixed physiologic level (50 copies) of artificially constructed, standard nonhuman reference DNA specific for each gene is introduced in a constant volume of serum (300 μL) before purification of the DNA, facilitating a sensitive, specific, robust, and quantitative assay of tumor DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in training (28 normal, 24 cancer) and test (27 normal, 33 cancer) sets of recurrent stage IV patient sera with a sensitivity of 91% and a specificity of 96% in the test set. In a pilot study, cMethDNA assay faithfully reflected patient response to chemotherapy (N = 29). A core methylation signature present in the primary breast cancer was retained in serum and metastatic tissues collected at autopsy two to 11 years after diagnosis of the disease. Together, our data suggest that the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden and treatment response in women with metastatic breast cancer. Cancer Res; 74(8); 2160–70. ©2014 AACR.