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Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, −2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy.British Journal of Cancer (2008) 98, 25–33. doi:10.1038/sj.bjc.6604092 www.bjcancer.com Published online 27 November 2007 [ABSTRACT FROM AUTHOR]

We evaluated quality of life (QL) and quality-adjusted survival in International Breast Cancer Study Group Trial IX, a randomised trial including 1669 eligible patients receiving tamoxifen for 5 years or three prior cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 57 months tamoxifen. During the time with CMF toxicity (Tox), without symptoms and toxicity (TWiST), and following relapse (Rel), patients scored their QL indicators and a utility indicator for subjective health estimation between 'perfect' and 'worst' health. Scores were averaged within Tox, TWiST and Rel and transformed to utilities. Mean durations for the three transition times were weighted with utilities to obtain mean quality-adjusted TWiST (Q-TWiST). Patients receiving CMF reported significantly worse scores for most QL domains at month 3, but less hot flushes. After completing chemotherapy, there were no differences by treatment groups. Benefits evaluated by Q-TWiST favoured the additional chemotherapy. CMF provided 3 more months of Q-TWiST for patients with ER-negative tumours, but CMF provided no benefit in Q-TWiST for patients with ER-positive tumours. Q-TWiST analysis based on patient ratings is feasible in large-scale cross-cultural clinical trials. [ABSTRACT FROM AUTHOR]

Objective To analyze data from a large group of patients enrolled in the International Breast Cancer Study Group (IBCSG) Trial in order to provide information about the prognostic significance of medially located primary breast cancers. [ABSTRACT FROM AUTHOR]

Abstract Background Primary human tissues are an invaluable widely used tool for discovery of gene expression patterns which characterize disease states. Tissue processing methods remain unstandardized, leading to unanswered concerns of how to best store collected tissues and maintain reproducibility between laboratories. We subdivided uterine myometrial tissue specimens and stored split aliquots using the most common tissue processing methods (fresh, frozen, RNALater) before comparing quantitative RNA expression profiles on the Affymetrix U133 human expression array. Split samples and inclusion of duplicates within each processing group allowed us to undertake a formal genome-wide analysis comparing the magnitude of result variation contributed by sample source (different patients), processing protocol (fresh vs. frozen vs. 24 or 72 hours RNALater), and random background (duplicates). The dataset was randomly permuted to define a baseline pattern of ANOVA test statistic values against which the observed results could be interpreted. Results 14,639 of 22,283 genes were expressed in at least one sample. Patient subjects provided the greatest sources of variation in the mixed model ANOVA, with replicates and processing method the least. The magnitude of variation conferred by processing method (24 hours RNALater vs 72 hours RNALater vs. fresh vs frozen) was similar to the variability seen within replicates. Subset analysis of the test statistic according to gene functional class showed that the frequency of "outlier" ANOVA results within each functional class is overall no greater than expected by chance. Conclusions Ambient storage of tissues for 24 or 72 hours in RNALater did not contribute any systematic shift in quantitative RNA expression results relative to the alternatives of fresh or frozen tissue. This nontoxic preservative enables decentralized tissue collection for expression array analysis without a requirement for specialized equipment.

Background: Knowing the predictive factors of the variation in a center-level continuous outcome of interest is valuable in the design and analysis of parallel-arm cluster randomized trials. The symbolic two-step method for sample size planning that we present incorporates this knowledge while simultaneously accounting for patient-level characteristics. Our approach is illustrated through application to cluster randomized trials in cancer care delivery research. The required number of centers (clusters) depends on the between- and within-center variance; the within-center variance is a function of estimates obtained by regressing the log within-center variance on predictive factors. Obtaining accurate estimates of the components needed to characterize the within-center variation is challenging., Methods: Using our previously derived sample size formula, our objective in the current research is to directly account for the imprecision in these estimates, using a Bayesian approach, to safeguard against designing an underpowered study when using the symbolic two-step method. Using estimates of the required components, including the number of centers that contribute to those estimates, we make formal allowance for the imprecision in these estimates on which a sample size will be based., Results: The mean of the distribution for power is consistently smaller than the single point estimate that the sample size formula yields. The reduction in power is more pronounced in the presence of increased uncertainty about the estimates with the reduction becoming more attenuated with increased numbers of centers that contribute to the estimates., Conclusions: Accounting for imprecision in the estimates of the components required for sample size estimation using the symbolic two-step method in the design of a cluster randomized trial yields conservative estimates of power., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Operable triple-negative breast cancer (TNBC) has a higher risk of recurrence and death compared to other subtypes. Tumor size and nodal status are the primary clinical factors used to guide systemic treatment, while biomarkers of proliferation have not demonstrated value. Recent studies suggest that subsets of TNBC have a favorable prognosis, even without systemic therapy. We evaluated the association of fully automated mitotic spindle hotspot (AMSH) counts with recurrence-free (RFS) and overall survival (OS) in two separate cohorts of patients with early-stage TNBC who did not receive systemic therapy. AMSH counts were obtained from areas with the highest mitotic density in digitized whole slide images processed with a convolutional neural network trained to detect mitoses. In 140 patients from the Mayo Clinic TNBC cohort, AMSH counts were significantly associated with RFS and OS in a multivariable model controlling for nodal status, tumor size, and tumor-infiltrating lymphocytes (TILs) (p < 0.0001). For every 10-point increase in AMSH counts, there was a 16% increase in the risk of an RFS event (HR 1.16, 95% CI 1.08-1.25), and a 7% increase in the risk of death (HR 1.07, 95% CI 1.00-1.14). We corroborated these findings in a separate cohort of systemically untreated TNBC patients from Radboud UMC in the Netherlands. Our findings suggest that AMSH counts offer valuable prognostic information in patients with early-stage TNBC who did not receive systemic therapy, independent of tumor size, nodal status, and TILs. If further validated, AMSH counts could help inform future systemic therapy de-escalation strategies., (© 2024. The Author(s).)

Background and Aims: Effective approaches for prevention of hepatocellular carcinoma (HCC) will have a significant impact on HCC-related mortality. There are strong preclinical data and rationale to support targeting epidermal growth factor receptor (EGFR) for HCC chemoprevention. Small molecule inhibitors of EGFR have been Food and Drug Administration-approved for cancer therapy, which provides an opportunity to repurpose one of these drugs for chemoprevention of HCC. Unfortunately, the frequency of side effects associated with administration of these drugs at oncology doses renders them ineffective for chemoprevention. This clinical trial assesses whether lower doses of one of these inhibitors, erlotinib, still engages EGFR in the liver to block signaling (eg, EGFR phosphorylation). The objective of this clinical trial was determination of a safe and minimum effective dose of erlorinib for which ≥ 50% reduction phospho-EGFR immunohistochemical staining in the liver was observed., Methods: Forty six participants were preregistered and 25 participants were registered in this multicenter trial. By dose de-escalation trial design, cohorts of participants received a 7-day course of erlotinib 75 mg/day, 50 mg/day or 25 mg/day with liver tissue acquisition prior to and after erlotinib., Results: A ≥50% reduction phospho-EGFR immunohistochemical staining in the liver was observed in a minimum of 40% of participants (predetermined threshhold) at each of the dose levels. Erlotinib was very well tolerated with few side effects observed, particularly at the dose of 25 mg/day. Favorable modulation of the Prognostic Liver Signature was observed in participants who received erlotinib., Conclusion: These data support the selection of erlotinib doses as low as 25 mg/day of for a longer intervention to assess for evidence of efficacy as an HCC chemoprevention drug (ClinicalTrials.govNCT02273362)., (© 2024 The Authors.)

Background: The Patient Cloud ePRO app was adopted by the National Cancer Institute National Clinical Trials Network (NCTN) to facilitate capturing electronic patient-reported (ePRO) outcome data, but use has been low. The study objectives were to test whether a patient-targeted ePRO educational resource (ePRO-E) would increase ePRO intent (number of users) and improve data quality (high quality: ≥80% of the required surveys submitted) within an ongoing NCTN study., Methods: The ePRO-E intervention, a patient-targeted educational resource (written material and 6-minute animated YouTube video), was designed to address ePRO barriers. ePRO intent and data quality were compared between 2 groups (N = 69): a historical control group and a prospectively recruited intervention group exposed to ePRO-E. Covariates included technology attitudes, age, sex, education, socioeconomic status, and comorbidity., Results: Intervention group ePRO intent (78.8%) was statistically significantly higher than historical control group intent (47.1%) (P = .03). Patients choosing ePRO versus paper surveys had more positive and higher technology attitudes scores (P = .03). The odds of choosing ePRO were 4.7 times higher (95% Confidence Interval [CI] = 1.2 to 17.8) (P = .02) among intervention group patients and 5.2 times higher (95% CI = 1.3 to 21.6) (P = .02) among patients with high technology attitudes scores, after controlling for covariates. However, the 80% submission rate (percentage submitting ≥80% of required surveys) in the ePRO group (30.6%) was statistically significantly lower than in the paper group (57.9%) (P = .05)., Conclusions: ePRO-E exposure increased ePRO intent. High technology attitudes scores were associated with ePRO selection. Since the ePRO survey submission rate was low, additional strategies are needed to promote high-quality data submission., (© The Author(s) 2024. Published by Oxford University Press.)

Pragmatic randomized clinical trials (pRCTs) have a unique set of considerations for data and safety monitoring. Because of their unconventional trial designs coupled with collection of multilevel data and implementation outcomes in real-world settings, thoughtful consideration is needed on the presentation of the trial design and accruing data to facilitate review and decision-making by the trial's data and safety monitoring board (DSMB). To our knowledge, there is limited information available in practical guidelines for generalists and medical general practitioners on what to monitor and to report to the DSMB during the conduct of pRCTs and what the DSMB should focus on in its review of reports. This article discusses these matters in the context of 3 case studies focusing on a set of critical data and safety monitoring questions that would be of interest to the generalist conducting pRCTs. In considering these questions, we provide tabular and graphical illustrations of how data can be presented to the DSMB while drawing attention to those areas that the DSMB should focus on in its review of the trial. The strategies and viewpoints discussed herein provide practical guidelines and can serve as a resource for the generalist conducting pRCTs., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Hormone receptor-positive (HR +) breast cancer is the most common type of breast cancer in the USA but has excellent long-term outcomes in recent decades, in part due to effective oral endocrine therapy (ET). ET medications are typically prescribed for 5 to 10 years, depending on the risk of recurrence, and must be taken daily. One limiting factor to ET efficacy is nonadherence, with high-risk groups for nonadherence including younger women and Black women., Methods: The Alliance for Clinical Trials in Oncology (Alliance) trial A191901 is an ongoing, four-arm (text message reminder (TMR), motivational interviewing (MI), TMR plus MI, or enhanced usual care) randomized clinical trial that tests the efficacy and effect of two interventions (TMR and/or MI) on improved ET adherence, patient-reported outcomes (PROs), and resource use requirements among HR + breast cancer survivors. Participants are randomized in a 1:1:1:1 ratio to the four arms. With an assumed loss to follow-up of approximately 11%, we plan to recruit 1180 participants. Randomization is stratified based on age and race to ensure balance between the arms, and we oversample younger and Black women, with each group representing 30% of the study population. Participants randomized to an intervention will actively participate in the intervention for 9 months, and all participants will be followed for adherence data and PRO endpoints, through the use of the Pillsy cap medication event monitoring system and Alliance ePRO survey app (i.e., Patient Cloud). The primary analysis will compare Pillsy-measured ET adherence among study arms at 12 months., Discussion: This multisite study will not only define strategies to improve adherence to breast cancer oral therapies, but it will also potentially support strategies in large cooperative research groups that can increase delivery and tolerability of ET, involve diverse patient populations in clinical research, and engage patients effectively in interventional studies, using remote and cost-effective delivery methods., Trial Registration: Clinicaltrials.gov NCT04379570 . Registered on 7 May 2020., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To describe clinical research professionals (CRPs)' experiences with electronic patient-reported outcome (ePRO) data collection systems in oncology clinical trials and identify correlates of CRPs' attitude toward technology., Methods: An online survey was conducted among 210 CRPs from 125 National Cancer Institute-funded research sites. Measures included CRPs' demographic characteristics, working years, employment locations, and previous experiences with various types of ePROs. Their attitude toward technology was measured by the Technology Attitude Scale-Adapted. The Wilcoxon signed-rank test was used to compare two subdomains of attitude (perceived usefulness [PU] and perceived ease of use [PEU]). Multiple linear regression was used to explore correlates of (1) overall attitude, (2) PU, and (3) PEU. The significance level was 5%., Results: Participants' median age was 41 years (range, 21-67). Most were female (90%) and White (82%). More than half of the participants had previous experiences with web-based ePROs using patients' own devices (72%) or site-/sponsor-provided on-site devices (eg, kiosks or tablets; 64%). CRPs who were 60 years or older (β = -0.32, P < .05) or worked for 10-20 years (β = -0.11, P < .05) had relatively negative attitudes, controlling for other factors. Previous experiences with more ePRO types were associated with more positive attitudes (β = 0.08, P = .02). Similar correlates were found with PU but not with PEU., Conclusion: This study revealed that CRPs had various experiences with ePRO systems and attitudes toward technology. Age, working years, and previous experiences with ePROs were correlates of overall attitude toward technology and PU. These findings suggest necessary targeted training to facilitate ePRO use in oncology clinical trials by improving CRPs' awareness and attitude toward technology.

Objective: To evaluate the role of timing (either before or during initial consultation) on the effectiveness of decision aids (DAs) to support shared-decision-making in a minority-enriched sample of patients with localized prostate cancer using a patient-level randomized controlled trial design., Methods: We conducted a 3-arm, patient-level-randomized trial in urology and radiation oncology practices in Ohio, South Dakota, and Alaska, testing the effect of preconsultation and within-consultation DAs on patient knowledge elements deemed essential to make treatment decisions about localized prostate cancer, all measured immediately following the initial urology consultation using a 12-item Prostate Cancer Treatment Questionnaire (score range 0 [no questions correct] to 1 [all questions correct]), compared to usual care (no DAs)., Results: Between 2017 and 2018, 103 patients-including 16 Black/African American and 17 American Indian or Alaska Native men-were enrolled and randomly assigned to receive usual care (n = 33) or usual care and a DA before (n = 37) or during (n = 33) the consultation. After adjusting for baseline characteristics, there were no statistically significant proportional score differences in patient knowledge between the preconsultation DA arm (0.06 knowledge change, 95% CI -0.02 to 0.12, P = .1) or the within-consultation DA arm (0.04 knowledge change, 95% CI -0.03 to 0.11, P = .3) and usual care., Conclusion: In this trial oversampling minority men with localized prostate cancer, DAs presented at different times relative to the specialist consultation showed no improvement in patient knowledge above usual care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naïve (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naïve TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers., (© 2023. The Author(s).)

Introduction: Nasal symptoms are frequently reported by patients undergoing chemotherapy., Methods: Eligible patients planning to receive paclitaxel, docetaxel, nab-paclitaxel, bevacizumab without a concomitant taxane, or "other" (non-taxane, non-bevacizumab) chemotherapy regimens were invited to participate in this prospective study. Patients reported nasal symptoms prior to each dose of chemotherapy., Results: The percentage of patients (95% CI) who reported nasal symptoms was the same for patients who received bevacizumab or nab-paclitaxel, 82.6% (61.2%, 95.1%). There were no significant differences among the proportions of patients experiencing nasal symptoms within the paclitaxel, nab-paclitaxel, and bevacizumab cohorts. Patients in the nab-paclitaxel cohort were more likely to experience symptoms than those in the non-taxane non-bevacizumab cohort or docetaxel cohort (p = 0.001, p = 0.001). Patients in the bevacizumab cohort were more likely to experience nasal symptoms than those in the non-taxane non-bevacizumab cohort (p = 0.03)., Conclusion: Nasal vestibulitis symptoms are common in patients receiving chemotherapy, especially those receiving paclitaxel, docetaxel, and bevacizumab. Further investigations into treatments of this symptom complex are warranted., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL12 DNA) as an addition to 6.0 mg of (INO-8000; HCV DNA vaccine). Vaccines were administered by intramuscular injection followed by electroporation at study entry and at weeks 4, 12, and 24. HCV-specific CD4+ and CD8+ T-cell immune responses were measured by IFNγ ELISpot and flow cytometry-based assays. Transient, mild-to-moderate injection site reactions unrelated to IL12 DNA dose were common. Increases in HCV-specific IFNγ production occurred in 15/20 (75%) participants. Increases in the frequency of HCV-specific CD4+ and CD8+ T cells occurred at all dose levels, with the greatest increases seen at 1.0 mg of INO-9012. HCV-specific CD8+ and CD4+ T-cell activities increased in 16/18 (89%) and 14/17 (82%) participants with available data, respectively. The vaccine regimen was safe and induced HCV-specific CD4+ and CD8+ cellular immune responses of modest magnitude in most HCV-infected participants. The addition of 1.0 mg of IL12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia., Prevention Relevance: The administration of IL12 DNA along with a hepatitis C viral antigen DNA vaccine enhanced the HCV-specific immune responses induced by the vaccine in individuals with chronic hepatitis C, an important cause of hepatocellular carcinoma. IL12 could be an effective adjuvant in vaccines targeting HCV and other oncogenic viruses., (©2022 American Association for Cancer Research.)

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate., Objective: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP., Design, Setting and Participants: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres., Exposures: Participants self-administered 350 mg of erlotinib by mouth, one time per week for 6 months., Main Outcomes and Measures: Duodenal polyp burden (sum of polyp diameters) was assessed in the proximal duodenum by esophagogastroduodenoscopy performed at baseline and 6 months, with mean per cent change defined as the primary efficacy outcome of interest. Rate of grade 2-3 AEs was evaluated as a co-primary outcome. Secondary outcomes included changes in total duodenal polyp count, along with changes in lower gastrointestinal (GI) polyp burden and count (for participants examined by optional lower endoscopy)., Results: Forty-six participants (mean age, 44.1 years (range, 18-68); women, 22 (48%)) were enrolled; 42 participants completed 6 months of intervention and were included in the per-protocol analysis. Duodenal polyp burden was significantly reduced after 6 months of weekly erlotinib intervention, with a mean per cent change of -29.6% (95% CI, -39.6% to -19.7%; p<0.0001). Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (mean, -27%; 95% CI, -38.7% to -15.2%; p<0.0001). Post-intervention Spigelman stage was downstaged in 12% of the participants. Lower GI polyp number was also decreased after 6 months of intervention (median, -30.8%; IQR, -47.4% to 0.0%; p=0.0256). Grade 2 or 3 AEs were reported in 71.7% of subjects, with only two experiencing grade 3 toxicity at least possibly related to intervention., Conclusion: In this single-arm, multi-centre trial of participants with FAP, erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower GI polyp burden, after 6 months of intervention. While AEs were still reported by nearly three-quarters of all participants, these events were generally lower grade and well-tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for FAP-associated GI polyposis., Trial Registration Number: NCT02961374., Competing Interests: Competing interests: PJL serves as Chief Medical Officer for Screening at Exact Sciences through a contracted services agreement with Mayo Clinic. PJL and Mayo Clinic have contractual rights to receive royalties through this agreement; Exact Sciences. JS is a consultant for Janssen Research and Development, Recursion Pharmaceuticals and Cancer Prevention Pharmaceuticals. CAB is a consultant for SLA pharma, Freenome, and has received research support from Janssen Pharmaceuticals, Cancer Prevention Pharmaceuticals, Ferring Pharmaceuticals and Emtora Biosciences. EV has a consulting or advisory role with Janssen Research and Development and Recursion Pharma and has received research support from Janssen Research and Development., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

mTOR inhibitors such as everolimus may cause oral stomatitis, often a dose-limiting toxicity. Prior clinical research has suggested that a dexamethasone mouth rinse might help prevent and/or treat this. Alliance A221701 was a randomized phase III trial of patients initiating 10 mg daily oral everolimus that compared dexamethasone mouthwash taken preventively (initial dexamethasone group) versus therapeutically (initial placebo group) to assess two coprimary endpoints: the incidence of mTOR inhibitor-associated stomatitis (mIAS), and the area under the curve (AUC) of mIAS-associated pain over an 8-week treatment period. A Fisher's exact test was used to compare the incidences while a Wilcoxon rank-sum test was used to compare the AUCs. In addition, we performed an exploratory analysis of the association of everolimus trough concentrations and toxicity using a Mann-Whitney U test. Due to slow accrual, this study closed after 39 patients were randomized (19 to upfront placebo and 20 to upfront dexamethasone). There were no significant differences between groups seen in either of the coprimary endpoints; furthermore, we found no association between whole blood everolimus trough concentrations and toxicity. Although limited by poor enrollment, the results of this study do not suggest that prophylactic dexamethasone mouthwash is superior to therapeutic dexamethasone mouthwash (initiated at the first sign of mouth pain) for reducing the incidence or severity of mIAS from everolimus., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Amplification of chromosome 9p24.1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes. However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in TNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non-metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.1 PDJ amplicon, 9q24.3, and 9q34.1. Samples with mean PDJ signal of > 4.5 copies, and ratios of PDJ/9q24 ≥ 2 and/or PDJ/9q34.1 ≥ 2 were called amplified (PDJ+). Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons in TNBCs. In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ- TNBCs. Matched pre- and post-neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status. Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon in TNBC., (© 2023. The Author(s).)

Background: Advances in precision medicine have given oncologists new evaluative tools to better individualize treatments for patients with curable breast cancer. These innovations have revealed a need to improve patient understanding of novel, often complex information related to breast cancer treatment decisions. Ensuring patients have the emotional support to face consequential treatment decisions, as well as the opportunity to engage and discuss with their clinicians, is key to improving patient-centered communication and patient understanding., Methods/design: This study will implement a multilevel intervention with patient and clinician components as a NCORP Cancer Care Delivery Research (CCDR) trial within the Alliance for Clinical Trials in Oncology Research Base (Alliance). The two interventions in this study, the Shared Decision Engagement System (SharES), include (1) two versions of an evidence-based patient-facing breast cancer treatment decision tool (iCanDecide +/- an emotional support module) and (2) a clinician-facing dashboard (Clinician Dashboard) that is reviewed by surgeons/clinicians and summarizes ongoing patient needs. The design is a near minimax, hybrid stepped wedge trial of SharES where both interventions are being evaluated in a crossed design over six 12-week time periods. The primary outcome (knowledge) and key secondary outcomes (i.e., self-efficacy and cancer worry) are assessed via patient report at 5 weeks after surgery. Secondary outcomes are also assessed at 5 weeks after surgery, as well as in a second survey 9 months after registration. We anticipate recruiting a total of 700 breast cancer patients (600 evaluable after attrition) from 25 surgical practices affiliated with Alliance., Discussion: Upon study completion, we will have better understanding of the impact of a multilevel intervention on patient-centered communication in breast cancer with a specific focus on whether the intervention components improve knowledge and self-efficacy and reduce cancer worry., Trial Registration: ClinicalTrials.gov NCT04549571 . Registered on 16 September 2020., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Socioeconomic disparities for breast cancer surgical care exist. Although the aetiology of the observed socioeconomic disparities is likely multifactorial, patient engagement during the surgical consult is critical. Shared decision-making may reduce health disparities by addressing barriers to patient engagement in decision-making that disproportionately impact socioeconomically disadvantaged patients. In this trial, we test the impact of a decision aid on increasing socioeconomically disadvantaged patients' engagement in breast cancer surgery decision-making., Methods and Analysis: This multisite randomised trial is conducted through 10 surgical clinics within the National Cancer Institute Community Oncology Research Program (NCORP). We plan a stepped-wedge design with clinics randomised to the time of transition from usual care to the decision aid arm. Study participants are female patients, aged ≥18 years, with newly diagnosed stage 0-III breast cancer who are planning breast surgery. Data collection includes a baseline surgeon survey, baseline patient survey, audio-recording of the surgeon-patient consultation, a follow-up patient survey and medical record data review. Interviews and focus groups are conducted with a subset of patients, surgeons and clinic stakeholders. The effectiveness of the decision aid at increasing patient engagement (primary outcome) is evaluated using generalised linear mixed-effects models. The extent to which the effect of the decision aid intervention on patient engagement is mediated through the mitigation of barriers is tested in joint linear structural equation models. Qualitative interviews explore how barriers impact engagement, especially for socioeconomically disadvantaged women., Ethics and Dissemination: This protocol has been approved by the National Cancer Institute Central Institutional Review Board, and Certificate of Confidentiality has been obtained. We plan to disseminate the findings through journal publications and national meetings, including the NCORP network. Our findings will advance the science of medical decision-making with the potential to reduce socioeconomic health disparities., Trial Registration Number: ClinicalTrials.gov Registry (NCT03766009)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Health-related quality of life (HRQoL) among patients with localized prostate cancer (PC) on active surveillance (AS) and whether it may be improved through lifestyle-focused interventions remain underdefined., Objective: To assess longitudinal changes in HRQoL in patients who received and those who did not receive a behavioral intervention that increased vegetable intake., Design, Setting, and Participants: A secondary analysis of participants in the Men's Eating and Living (MEAL) study (Cancer and Leukemia Group 70807 [Alliance]), a randomized trial of vegetable consumption in patients on AS, was conducted., Outcome Measurements and Statistical Analysis: Patient-reported outcomes (PROs) included the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), the Expanded Prostate Cancer Index Composite 26 (EPIC-26), and the Functional Assessment of Cancer Therapy Scale-Prostate (FACT-P). Areas under the curves (AUCs) were used to summarize serial HRQoL., Results and Limitations: PROs were completed in 87% (n = 387) of the intention-to-collect population. Baseline characteristics of patients completing HRQoL measures did not differ significantly from the entire study population or between groups. Baseline scores were high for all PROs and remained stable over 24 mo, with no significant differences from baseline at any time point. In adjusted analyses, there were no significant differences in summary AUC measures comparing control with intervention for the total MAX-PC score (p = 0.173); EPIC-26 domains of urinary incontinence (p = 0.210), urinary obstruction (p = 0.062), bowel health (p = 0.607), sexual health (p = 0.398), and vitality (p = 0.363); and total FACT-P scores (p = 0.471)., Conclusions: Among men with localized PC on AS enrolled in a randomized trial, HRQoL was high across multiple domains at baseline, remained high during follow-up, and did not change in response to a behavioral intervention that increased vegetable intake., Patient Summary: Patients with localized prostate cancer enrolled on active surveillance experience minimal cancer-associated anxiety, suffer low levels of cancer-associated symptoms, and perceive high physical and emotional well-being., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Alliance for Clinical Trials in Oncology (Alliance) coordinated trials utilize Medidata Rave® (Rave) as the primary clinical data capture system. A growing number of innovative and complex cancer care delivery research (CCDR) trials are being conducted within the Alliance with the aims of studying and improving cancer-related care. Because these trials encompass patients, providers, practices, and their interactions, a defining characteristic of CCDR trials is multilevel data collection in pragmatic settings. Consequently, CCDR trials necessitated innovative strategies for database development, centralized data management, and data monitoring in the presence of these real-world multilevel relationships. Having real trial experience in working with community and academic centers, and having recently implemented five CCDR trials in Rave, we are committed to sharing our strategies and lessons learned in implementing such pragmatic trials in oncology., Methods: Five Alliance CCDR trials are used to describe our approach to analyzing the database development needs and the novel strategies applied to overcome the unanticipated challenges we encountered. The strategies applied are organized into 3 categories: multilevel (clinic, clinic stakeholder, patient) enrollment, multilevel quantitative and qualitative data capture, including nontraditional data capture mechanisms being applied, and multilevel data monitoring., Results: A notable lesson learned in each category was (1) to seek long-term solutions when developing the functionality to push patient and non-patient enrollments to their respective Rave study database that affords flexibility if new participant types are later added; (2) to be open to different data collection modalities, particularly if such modalities remove barriers to participation, recognizing that additional resources are needed to develop the infrastructure to exchange data between that modality and Rave; and (3) to facilitate multilevel data monitoring, orient site coordinators to the their trial's multiple study databases, each corresponding to a level in the hierarchy, and remind them to establish the link between patient and non-patient participants in the site-facing NCI web-based enrollment system., Conclusion: Although the challenges due to multilevel data collection in pragmatic settings were surmountable, our shared experience can inform and foster collaborations to collectively build on our past successes and improve on our past failures to address the gaps., (© 2022. The Author(s).)

Importance: Standard treatment for resectable non-small cell lung cancer (NSCLC) includes anatomic resection with adequate lymph node dissection and adjuvant chemotherapy for appropriate patients. Historically, many patients with early-stage NSCLC have not received such treatment, which may affect the interpretation of the results of adjuvant therapy trials., Objective: To ascertain patterns of guideline-concordant treatment among patients enrolled in a US-wide screening protocol for adjuvant treatment trials for resected NSCLC., Design, Setting, and Participants: This retrospective cohort study included 2833 patients with stage IB to IIIA NSCLC (per American Joint Committee on Cancer 7th edition criteria) who enrolled in the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) screening study (Alliance for Clinical Trials in Oncology A151216) from August 18, 2014, to April 1, 2019, and who did not enroll in a therapeutic adjuvant clinical trial; patients had tumors of at least 4 cm and/or with positive lymph nodes. Statistical analysis was conducted from June 1, 2020, through October 1, 2021., Exposures: Care patterns were ascertained overall and by sociodemographic and clinical factors, including age, sex, race and ethnicity, educational level, marital status, geography, histologic characteristics, stage, genomic variant status, smoking history, and comorbidities., Main Outcomes and Measures: Five outcomes are reported: whether patients (1) had anatomic surgical resection, (2) had adequate lymph node dissection (≥1 N1 nodal station plus ≥3 N2 nodal stations), (3) received any adjuvant chemotherapy, (4) received any cisplatin-based adjuvant chemotherapy, and (5) received at least 4 cycles of adjuvant chemotherapy., Results: Of the 2833 patients (1505 women [53%]; mean [SD] age, 66.5 [9.2] years) included in this analysis, 2697 (95%) had anatomic surgical resection, 1513 (53%) had adequate lymph node dissection, 1617 (57%) received any adjuvant chemotherapy, 1237 (44%) received at least 4 cycles of adjuvant platinum-based chemotherapy, and 965 (34%) received any cisplatin-based adjuvant chemotherapy. Rates were similar across race and ethnicity., Conclusions and Relevance: This cohort study found that among participants in a screening protocol for adjuvant clinical trials for resected early-stage NSCLC, just 53% underwent adequate lymph node dissection, and 57% received adjuvant chemotherapy, despite indications for such treatment. These results may affect the interpretation of adjuvant trials. Efforts are needed to optimize the use of proven therapies for early-stage NSCLC., Trial Registration: ClinicalTrials.gov Identifier: NCT02194738.

Background: Decision aids (DAs) can improve knowledge for prostate cancer treatment. However, the relative effects of DAs delivered within the clinical encounter and in more diverse patient populations are unknown. A multicenter cluster randomized controlled trial with a 2×2 factorial design was performed to test the effectiveness of within-visit and previsit DAs for localized prostate cancer, and minority men were oversampled., Methods: The interventions were delivered in urology practices affiliated with the NCI Community Oncology Research Program Alliance Research Base. The primary outcome was prostate cancer knowledge (percent correct on a 12-item measure) assessed immediately after a urology consultation., Results: Four sites administered the previsit DA (39 patients), 4 sites administered the within-visit DA (44 patients), 3 sites administered both previsit and within-visit DAs (25 patients), and 4 sites provided usual care (50 patients). The median percent correct in prostate cancer knowledge, based on the postvisit knowledge assessment after the intervention delivery, was as follows: 75% for the pre+within-visit DA study arm, 67% for the previsit DA only arm, 58% for the within-visit DA only arm, and 58% for the usual-care arm. Neither the previsit DA nor the within-visit DA had a significant impact on patient knowledge of prostate cancer treatments at the prespecified 2.5% significance level (P = .132 and P = .977, respectively)., Conclusions: DAs for localized prostate cancer treatment provided at 2 different points in the care continuum in a trial that oversampled minority men did not confer measurable gains in prostate cancer knowledge., (© 2021 American Cancer Society.)

Background: A recently developed two-step method provides an alternative to single-step methods in the analysis of cluster randomized trials (CRTs). This method, called the symbolic two-step method because it was developed within the symbolic data analysis framework, adjusts for patient-level factors when estimating and testing effects of center-level factors on both the average center-level outcome and its variation. Estimation/testing of center-level effects on center-outcome variation is the innovation of the method; identifying such effects may lead to practice changes to reduce such variation. We evaluated the performance of our method in challenging settings and recommend when this method is preferred over single-step methods., Methods: The method was compared to single-step multilevel linear models - one that permitted heterogeneous within-center variances and one that did not - via simulation. We applied each method to a CRT., Results: After adjusting for patient-level factors in the setting of varying center sizes without any correlation between patient and center-level factors, the single-step models led to increased statistical power for center-level factors. In the presence of correlation, our method was more powerful. Applying these methods to model the center-mean outcome from the CRT led to similar conclusions; however, because the two-step method also models the within-center variability of that outcome we identified a factor predicting the within-center variance that was not possible with the single-step methods., Conclusions: We recommend single-step methods under the restrictive assumptions of no correlation between patient- and center-level factors and no center-level factor affecting center-outcome variation. Otherwise, we recommend the symbolic two-step method., (Copyright © 2022 Elsevier Inc. All rights reserved.)

While oxaliplatin-induced peripheral neuropathy (OIPN) is more common and severe in patients who receive the previous standard, 6-month oxaliplatin-based treatment, we hypothesized that OIPN was still pervasive in patients who received shorter, 3-month-treatment regimens. Using six EORTC QLQ-CIPN20 questions that quantify numbness (N), tingling (T) and shooting/burning pain (P) in upper/lower distal extremities, our aim is to quantify patient-reported responses over 3 months (6 cycles) of oxaliplatin regarding symptom-specific timing, location and severity. For each question, patients were asked how each of the sensory symptoms had affected them during the preceding week, with 1 = “Not at all”, 2 = “A little”, 3 = “Quite a bit” and 4 = “Very much”. The proportional odds model for the cumulative log odds of response that allowed symptom-specific patient heterogeneity to be obtained was applied to a pooled dataset from the placebo arms of two multisite OIPN prevention trials and fit separately to the upper/lower distal extremities. For each symptom, we report the cycle-specific marginal probabilities for each response. In 141 patients, substantial patient heterogeneity in the likelihood, at a given cycle, of a more severe response for a symptom was present. Distinct patterns in the probabilities for each response over time for N and T were observed between the upper/lower distal extremities, while the probabilities of a response >1 for P was largely negligible in both locations. Despite the decrease in exposure to oxaliplatin from 6 to 3 months, OIPN was still pervasive with patients experiencing considerable N and T in the fingers (or hands) and toes (or feet).

Purpose: To describe the natural history of nasal vestibulitis in patients receiving taxane chemotherapy, including incidence, severity, and associated symptoms., Methods: Eligible patients with minimal or no baseline nasal symptoms were enrolled in this natural history study at initiation of a new chemotherapy regimen. Patients completed nasal symptom logs each time they received a chemotherapy dose. This manuscript reports upon the patients who received paclitaxel, docetaxel, or non-taxane non-bevacizumab chemotherapy. The proportions of patients within each cohort reporting any treatment-emergent nasal symptoms were estimated, with corresponding exact 95% confidence intervals. A cumulative incidence function was estimated within the chemotherapy cohorts to calculate the cumulative incidence rate of treatment-emergent nasal vestibulitis, treating death and disease progression as competing risks., Results: Of the 81 evaluable patients, nasal symptoms were reported by 76.5% (58.8%, 89.3%) receiving paclitaxel, 54.2% (32.8%, 74.5%) receiving docetaxel, and 47.8% (26.8%, 69.4%) receiving non-taxane and non-bevacizumab chemotherapy. Of the three pairwise chemotherapy group comparisons, both the tests comparing the cumulative incidence function between the paclitaxel and non-taxane non-bevacizumab chemotherapy cohorts and between the paclitaxel and docetaxel cohorts achieved statistical significance at the 5% level with a higher incidence of treatment-emergent nasal vestibulitis in the paclitaxel cohort in both comparisons (P = 0.026 and P = 0.035, respectively). These significant differences were retained in the cumulative incidence function regression analysis controlling for age, smoking history, allergies, and asthma. Most patients in the paclitaxel cohort reported nasal symptoms as moderate or severe (56%)., Conclusion: Patients receiving paclitaxel chemotherapy experience a high incidence of nasal symptoms., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the presence of a placebo dose-response effect in four randomized, double-blind, placebo-controlled, multi-dose hot flash clinical trials conducted at Mayo Clinic., Methods: Hot flash score, frequency, and hot flash-related distress for each placebo dose level were summarized at each time point by mean and standard deviation and changes from baseline were plotted to visualize a possible placebo dose-effect response. Furthermore, a meta-analysis was conducted for each endpoint in the highest and lowest dosage arms across the four trials., Results: Longitudinal plots of mean hot flash scores, frequencies, and hot flash-related distress scores in patients taking placebo in each study showed a decline in hot flash scores over time without any clinically meaningful differences between the lowest and highest dosage arms in each study. The meta-analysis for each endpoint in the highest and lowest dosage arms across the four trials revealed no clinically important differences either., Conclusion: While the current study cannot rule out the existence of a placebo dose-response effect in multi-dose placebo-controlled trials in patients with hot flashes or other conditions, it suggests, along with the available data in the placebo literature, that, at least in well-conducted multi-dose clinical trials in which the placebo was used as control, such an effect, if it exists at all, should be very small. Therefore, pooling data from different placebo subgroups is unlikely to compromise the validity of comparisons between the combined placebo arms and each treatment arm., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Programmed death ligand 1 [PD-(L)1]-targeted therapies have shown modest survival benefit in triple-negative breast cancer (TNBC). PD-L1 + microenvironments in TNBC are not well characterized and may inform combinatorial immune therapies. Herein, we characterized clinicopathologic features, RNA-based immune signatures, and spatially defined protein-based tumor-immune microenvironments (TIME) in early-stage PD-L1 + and PD-L1 - TNBC., Experimental Design: From a large cohort of chemotherapy-naïve TNBC, clinicopathologic features, deconvoluted RNA immune signatures, and intraepithelial and stromal TIME (Nanostring GeoMX) were identified in subsets of PD-L1 + and PD-L1 - TNBC, as defined by FDA-approved PD-L1 companion assays., Results: 228 of 499 (46%) TNBC were PD-L1 + (SP142: ≥1% immune cells-positive). Using PD-L1 22C3, 46% had combined positive score (CPS) ≥ 1 and 16% had CPS ≥10. PD-L1 + TNBC were higher grade with higher tumor-infiltrating lymphocytes (TIL; P < 0.05). PD-L1 was not associated with improved survival following adjustment for TILs and other variables. RNA profiles of PD-L1 + TNBC had increased dendritic cell, macrophage, and T/B cell subset features; and decreased myeloid-derived suppressor cells. PD-L1+ stromal and intraepithelial TIMEs were highly enriched in IDO-1, HLA-DR, CD40, and CD163 compared with PD-L1-TIME, with spatially specific alterations in CTLA-4, Stimulator of Interferon Genes (STING), and fibronectin. Macrophage- and antigen presentation-related proteins correlated most strongly with PD-L1 protein., Conclusions: In this early-stage TNBC cohort, nearly 50% were PD-L1 + (SP142 companion assay) while 16% were PD-L1 + with the 22C3 companion assay. PD-L1 + TNBC had specific myeloid-derived and lymphoid features. Spatially defined PD-L1 + TIME were enriched in several clinically actionable immune proteins. These data may inform future studies on combinatorial immunotherapies for patients with PD-L1 + TNBC. See related commentary by Symmans, p. 5446 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects. This study evaluates the effect of 1-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with ≥25% MD and no history of cancer were randomly assigned to 2,000 international units (IU) of vitamin D or placebo orally daily for 1 year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between January 2011 and December 2013 with a mean age of 43 and diverse ethnicity [14% Hispanic, 12% African American (AA)]. Supplementation significantly increased vitamin D levels compared with placebo (14.5 ng/mL vs. -1.6 ng/mL; P < 0.0001) with all participants on the vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs. placebo) at 1 year was -0.75 (-0.26, 1.76; P = 0.56). A greater effect was seen for women with ≥50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2,000 IU for 1 year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study). PREVENTION RELEVANCE: Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and are underutilized due to toxicity and side effects. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects., (©2021 American Association for Cancer Research.)

Introduction: Optimal treatment for older adults with stage III non-small cell lung cancer (NSCLC) remains unclear. Here we hypothesized that sequential chemoradiation therapy (sCRT) is better tolerated than concurrent (cCRT) but confers acceptable efficacy. We evaluated these strategies in older adults utilizing Alliance for Clinical Trials in Oncology data., Materials and Methods: Pooled analyses from 6 first-line stage III NSCLC CRT trials (Cancer and Leukemia Group B 8433, 8831, 9130, 30106, 30407, 39801) were used to compare toxicity and survival outcomes with cCRT versus sCRT in patients age ≥ 65 years. Grade 3-5 adverse events (AEs), progression-free and overall survival (PFS; OS) are reported with adjustment for covariates., Results: Four hundred older adults, of whom 106 (26.5%) had received sCRT and 294 (73.5%) had received cCRT, comprised the cohorts. Virtually all had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 (99%). More grade 3-5 AEs were observed at any time-point with cCRT than sCRT (94.2% versus 86.8%; 95% confidence interval for difference in proportions, 1.3%, 15.5%) and this finding remained after adjusting for length of study treatment (P = 0.018). Comparable PFS and OS were observed with sCRT versus cCRT (median: 8.0 versus 9.2 months; median: 11.9 versus 13.4 months, respectively) even after adjustment for age, sex, ECOG PS, body mass index, pretreatment weight loss, stage, and cisplatin-based therapy (P = 0.604 and P = 0.906, respectively)., Discussion: These data show that sCRT was associated with less toxicity than cCRT with no associated statistically significant decrease in efficacy outcomes and that sCRT merits further study in this population., Competing Interests: Declaration of Competing Interest Dr. Wong has reported a conflict of interest outside of the submitted work (immediate family member is an employee of Genentech with stock ownership). No other authors have reported a conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The incidence of breast cancer among non-Hispanic American Indian and Alaska Native (AI/AN) women varies across the United States. We applied county-level Bayesian disease mapping to quantify potential inequities in 10-year breast cancer incidence in New Mexico to better inform health equity initiatives among its non-Hispanic at-risk AI/AN population., Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) program from 2005 through 2014 to identify new cases of breast cancer in New Mexico's 33 counties. To account for spatial variation, a county-level Area Deprivation Index, and the small area estimation problem inherent in these data, we borrowed strength globally and locally by applying Bayesian disease mapping to the counts of age-adjusted county-level breast cancer incidence. We quantified the disparity effect, as measured by the age-adjusted rate ratio, comparing the incidence of breast cancer between at-risk non-Hispanic AI/AN and non-Hispanic White women and assessed whether the ratio differed among counties., Results: Accounting for over-dispersion and spatial correlation among the 33 counties and a county-level Area Deprivation Index, the posterior mean of the overall age-adjusted rate ratio was 0.384 (95% credible interval, 0.253--0.546). The age-adjusted rate of breast cancer in non-Hispanic AI/AN women was 0.38 times the corresponding age-adjusted rate for non-Hispanic White women; however, a significant reduction in breast cancer incidence was observed in 16 of the 33 counties., Conclusion: The application of Bayesian disease mapping to these data provided substantial evidence of an overall disparity in breast cancer incidence between at-risk non-Hispanic AI/AN and non-Hispanic White women in New Mexico, which was more marked than previously reported and limited to certain counties. Targeted statewide and county-level health-equity initiatives may lead to a reduction in these disparities.