Rural resilience during COVID-19: the lived experience of North Carolinian rural-dwelling cancer caregivers.

PURPOSE: To illuminate the lived experience of resilience in rural-dwelling North Carolinian cancer caregivers at the intersection of cancer and the COVID-19 pandemic. METHODS: In spring, 2020, we recruited self-identified primary caregivers (CGs) for a relative/friend with cancer living in a rural area. We conducted cross-sectional semi-structured interviews and then thematically analyzed transcripts to identify and categorize instances of stressors and benefit-finding. RESULTS: Of the 24 participants, 29% were < 50 years old, 42% identified as non-Hispanic Black, 75% were women, and 58% were spousal CGs. Most care recipients (CRs) had stage IV cancer (n = 20) and cancer types varied. Participants played a variety of roles in caregiving and experienced stressors related to caregiving demands (e.g., conflicts with other responsibilities), rurality (e.g., transportation), and the COVID-19 pandemic (e.g., new visitor policy at hospital). Despite stressful experiences, participants also identified many positive aspects of their caregiving. Five domains of benefit-finding were identified: appreciation (e.g., gratitude toward their ability to care for CRs), CG-CR dyad relationship dynamics (e.g., increased closeness), interpersonal relationship dynamics (e.g., perceived peer support), faith (e.g., ability to cope through praying), and personal growth (e.g., new skills learned from caregiving). CONCLUSION: Rural-dwelling cancer caregivers from mixed sociodemographic backgrounds identified a diverse range of benefits from caregiving, despite experiencing multiple stressors, including emergent stressors from the COVID-19 pandemic. Healthcare delivery serving rural communities may consider expanding transportation assistance and boosting benefit-finding to ameliorate stress in cancer caregivers.

Clinicopathologic and sociodemographic factors associated with late relapse triple negative breast cancer in a multivariable logistic model: A multi-institution cohort study.

BACKGROUND: Most metastatic recurrences of triple negative breast cancer (TNBC) occur within five years of diagnosis, yet late relapses of TNBC (lrTNBC) do occur. Our objective was to develop a risk prediction model of lrTNBC using readily available clinicopathologic and sociodemographic features. METHODS: We included patients diagnosed with stage I-III TNBC between 1998 and 2012 at ten academic cancer centers. lrTNBC was defined as relapse or mortality greater than 5 years from diagnosis. Features associated with lrTNBC were included in a multivariable logistic model using backward elimination with a p < 0.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts. RESULTS: A total 2210 TNBC patients with at least five years follow-up and no relapse before 5 years were included. In final multivariable model, lrTNBC was significantly associated with higher stage at diagnosis (adjusted Odds Ratio [aOR] for stage III vs I, 10.9; 95% Confidence Interval [CI], 7.5-15.9; p < 0.0001) and BMI (aOR for obese vs normal weight, 1.4; 95% CI, 1.0-1.8; p = 0.03). Final model performance was consistent between training (70%) and validation (30%) cohorts. CONCLUSIONS: A risk prediction model incorporating stage, BMI, and age at diagnosis offers potential utility for identification of patients at risk of development of lrTNBC and warrants further investigation.

"If I wasn't in a rural area, I would definitely have more support": social needs identified by rural cancer caregivers and hospital staff.

BACKGROUND: The social needs of rural families facing cancer warrant investigation to inform psychosocial care planning and policy development. METHODS: Using purposive sampling, we interviewed 24 rural caregivers and 17 hospital staff from an academic cancer center in the U.S. South. Social needs were defined as the support needed to effectively provide informal caregiving across economic, physical, interpersonal, and service domains. We used the framework method to code and synthesize findings. FINDINGS: Caregiver economic and physical needs were interconnected and most pressing, including common examples of distance to care and transportation barriers. Caregivers desired additional support from the health system, insurance providers, and community resources. Staff identified similar need patterns and gaps in health system capacity. CONCLUSIONS: Rural cancer caregivers experience multiple unmet social needs. Supportive interventions for this population will benefit from flexible implementation and multilevel, multisector approaches. In particular, interventions that address financial hardship and limited internet access are needed.

Association of body mass index and inflammatory dietary pattern with breast cancer pathologic and genomic immunophenotype in the nurses' health study.

BACKGROUND: Breast tumor immune infiltration is clearly associated with improved treatment response and outcomes in breast cancer. However, modifiable patient factors associated with breast cancer immune infiltrates are poorly understood. The Nurses' Health Study (NHS) offers a unique cohort to study immune gene expression in tumor and adjacent normal breast tissue, immune cell-specific immunohistochemistry (IHC), and patient exposures. We evaluated the association of body mass index (BMI) change since age 18, physical activity, and the empirical dietary inflammatory pattern (EDIP) score, all implicated in systemic inflammation, with immune cell-specific expression scores. METHODS: This population-based, prospective observational study evaluated 882 NHS and NHSII participants diagnosed with invasive breast cancer with detailed exposure and gene expression data. Of these, 262 women (training cohort) had breast tumor IHC for four classic immune cell markers (CD8, CD4, CD20, and CD163). Four immune cell-specific scores were derived via lasso regression using 105 published immune expression signatures' association with IHC. In the remaining 620 patient evaluation cohort, we evaluated association of each immune cell-specific score as outcomes, with BMI change since age 18, physical activity, and EDIP score as predictors, using multivariable-adjusted linear regression. RESULTS: Among women with paired expression/IHC data from breast tumor tissue, we identified robust correlation between novel immune cell-specific expression scores and IHC. BMI change since age 18 was positively associated with CD4+ (ß = 0.16; p = 0.009), and CD163 novel immune scores (ß = 0.14; p = 0.04) in multivariable analyses. In other words, for each 10 unit (kg/m2) increase in BMI, the percentage of cells positive for CD4 and CD163 increased 1.6% and 1.4%, respectively. Neither physical activity nor EDIP was significantly associated with any immune cell-specific expression score in multivariable analyses. CONCLUSIONS: BMI change since age 18 was positively associated with novel CD4+ and CD163+ cell scores in breast cancer, supporting further study of the effect of modifiable factors like weight gain on the immune microenvironment.

Luminal androgen receptor breast cancer subtype and investigation of the microenvironment and neoadjuvant chemotherapy response.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with low overall survival rates and high molecular heterogeneity; therefore, few targeted therapies are available. The luminal androgen receptor (LAR) is the most consistently identified TNBC subtype, but the clinical utility has yet to be established. Here, we constructed a novel genomic classifier, LAR-Sig, that distinguishes the LAR subtype from other TNBC subtypes and provide evidence that it is a clinically distinct disease. A meta-analysis of seven TNBC datasets (n = 1086 samples) from neoadjuvant clinical trials demonstrated that LAR patients have significantly reduced response (pCR) rates than non-LAR TNBC patients (odds ratio = 2.11, 95% CI: 1.33, 2.89). Moreover, deconvolution of the tumor microenvironment confirmed an enrichment of luminal epithelium corresponding with a decrease in basal and myoepithelium in LAR TNBC tumors. Increased immunosuppression in LAR patients may lead to a decreased presence of cycling T-cells and plasma cells. While, an increased presence of myofibroblast-like cancer-associated cells may impede drug delivery and treatment. In summary, the lower levels of tumor infiltrating lymphocytes (TILs), reduced immune activity in the micro-environment, and lower pCR rates after NAC, suggest that new therapeutic strategies for the LAR TNBC subtype need to be developed.

Guidance to Support the Implementation of Specialized Adolescent and Young Adult Cancer Care: A Qualitative Analysis of Cancer Programs.

PURPOSE: The nearly 90,000 adolescents and young adults (AYAs) diagnosed with cancer in the United States yearly have tended to occupy a no-man's land between medical and pediatric oncology, often reporting that existing models of care are misaligned with their needs and preferences. Although guidelines for optimal AYA cancer care are increasingly available, the implementation of such standards has been varied. This may be in part due to a lack of guidance for implementing specialized AYA care. In this study, we leveraged an implementation science framework to identify barriers and generate practical guidance to inform the implementation of specialized AYA cancer care. METHODS: We conducted semistructured qualitative interviews, guided by the Consolidated Framework for Implementation Research, with AYA care stakeholders (N = 32 from 14 cancer programs). Our multidisciplinary research team analyzed interview transcriptions using a template analysis approach and gleaned from interviews practical guidance for implementing specialized AYA care. RESULTS: Participants reported barriers to implementing specialized AYA care across all five Consolidated Framework for Implementation Research domains: (1) intervention characteristics (eg, costs), (2) inner setting (eg, difficulties in collaborating between pediatric and medical oncology), (3) outer setting (eg, patient-level barriers to participating in AYA services), (4) individual characteristics (eg, attitudes about AYA oncology), and (5) process (eg, lack of metrics for program evaluation). They also shared practical guidance for addressing these barriers. CONCLUSION: Emerging guidance on the core elements of AYA cancer care must be matched with guidance to support the implementation of specialized AYA care. This study contributes to the body of evidence available to inform future implementation efforts.

Identifying Strategies for Robust Survivorship Program Implementation: A Qualitative Analysis of Cancer Programs.

PURPOSE: The Commission on Cancer seeks to promote robust survivorship programs among accredited cancer programs. In practice, cancer programs' survivorship programs range from cursory (eg, developing care plans without robust services) to robust (eg, facilitating follow-up care). To inform cancer programs' future efforts, in this study, we identified the implementation strategies that cancer programs used to achieve robust survivorship programs, distinguishing them from cursory programs. METHODS: We sampled 39 cancer programs across the United States with approaches to survivorship program implementation ranging from cursory to robust on the basis of LIVESTRONG survivorship care consensus elements. Within sampled cancer programs, we conducted in-depth semistructured interviews with a total of 42 health care professionals. We used template analysis to distinguish implementation strategies used in cancer programs with robust survivorship programs from strategies that yielded cursory survivorship programs. RESULTS: Cancer programs with robust survivorship programs established clear systems survivorship care and formal committees to improve the survivorship care processes. They sought buy-in from multiple stakeholders to leverage cancer program resources and defined clear roles with shared accountability among multidisciplinary groups. By contrast, cancer programs with cursory survivorship programs reported less consistency in survivorship care processes and lacked buy-in from key stakeholders. They had limited resources, faced persistent structural concerns, and had insufficient clarity in roles among team members. CONCLUSION: Accrediting bodies may consider incorporating the implementation strategies that robust survivorship programs have used as guidance for supporting cancer programs in operationalizing survivorship care and evaluating the use of these strategies during the accreditation and review process.

Association of 17q22 Amplicon Via Cell-Free DNA With Platinum Chemotherapy Response in Metastatic Triple-Negative Breast Cancer.

PURPOSE: To determine whether specific somatic copy-number alterations detectable in circulating tumor DNA (ctDNA) from patients with metastatic triple-negative breast cancer (mTNBC) are associated with sensitivity to platinum chemotherapy. MATERIALS AND METHODS: In this secondary analysis of a large cohort of patients with mTNBC whose ctDNA underwent ultralow-pass whole-genome sequencing, tumor fraction and somatic copy-number alterations were derived with the ichorCNA algorithm. Seventy-two patients were identified who had received a platinum-based chemotherapy regimen in the metastatic setting. Gene-level copy-number analyses were performed with GISTIC2.0. Cytobands were associated with progression-free survival (PFS) to platinum chemotherapy using Cox proportional hazards models. The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium data sets were interrogated for frequency of significant cytobands in primary triple-negative breast cancer (pTNBC) tumors. RESULTS: Among 71 evaluable patients, 17q21 and 17q22 amplifications were most strongly associated with improved PFS with platinum chemotherapy. There were no significant differences in clinicopathologic features or (neo)adjuvant chemotherapy among patients with 17q22 amplification. Patients with 17q22 amplification (n = 17) had longer median PFS with platinum (7.0 v 3.8 months; log-rank P = .015) than patients without 17q22 amplification (n = 54), an effect that remained significant in multivariable analyses (PFS hazard ratio 0.37; 95% CI, 0.16 to 0.84; P = .02). Among 39 patients who received the nonplatinum chemotherapy agent capecitabine, there was no association between 17q22 amplification and capecitabine PFS (log-rank P = .69). In The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium, 17q22 amplification occurred in more than 20% of both pTNBC and mTNBC tumors, whereas 17q21 was more frequently amplified in mTNBC relative to pTNBC (16% v 8.1%, P = .015). CONCLUSION: The 17q22 amplicon, detected by ctDNA, is associated with improved PFS with platinum chemotherapy in patients with mTNBC and warrants further investigation.

Matched cohort study of germline BRCA mutation carriers with triple negative breast cancer in brightness.

In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls (n = 150) by treatment arm, lymph node status, and age to evaluate pCR rates and association of benefit from platinum/PARP inhibitors with validated RNA expression-based immune, proliferation, and genomic instability scores among gBRCA with the addition of carboplatin ± veliparib to NAC. Among the well-matched cohorts, odds of pCR were not higher in gBRCA cancers who received standard NAC with carboplatin (OR 0.24, 95% CI [0.04-1.24], p = 0.09) or with carboplatin/veliparib (OR 0.44, 95% CI [0.10-1.84], p = 0.26) compared to non-gBRCA cancers. Higher PAM50 proliferation, GeparSixto immune, and CIN70 genomic instability scores were each associated with higher pCR rate in the overall cohort, but not specifically in gBRCA cases. In this study, gBRCA carriers did not have higher odds of pCR than non-gBRCA controls when carboplatin ± veliparib was added to NAC, and showed no significant differences in molecular, immune, chromosomal instability, or proliferation gene expression metrics.

Genomic features of rapid versus late relapse in triple negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors. METHODS: Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as 'rapid relapse' (rrTNBC; distant relapse or death ≤2 years of diagnosis), 'late relapse' (lrTNBC; > 2 years) or 'no relapse' (nrTNBC: > 5 years no relapse/death). We explored basic clinical and primary tumor multi-omic data, including whole transcriptome (n = 453), and whole genome copy number and mutation data for 171 cancer-related genes (n = 317). Association of rapid relapse with clinical and genomic features were assessed using Pearson chi-squared tests, t-tests, ANOVA, and Fisher exact tests. We evaluated logistic regression models of clinical features with subtype versus two models that integrated significant genomic features. RESULTS: Relative to nrTNBC, both rrTNBC and lrTNBC had significantly lower immune signatures and immune signatures were highly correlated to anti-tumor CD8 T-cell, M1 macrophage, and gamma-delta T-cell CIBERSORT inferred immune subsets. Intriguingly, lrTNBCs were enriched for luminal signatures. There was no difference in tumor mutation burden or percent genome altered across groups. Logistic regression mModels that incorporate genomic features significantly outperformed standard clinical/subtype models in training (n = 63 patients), testing (n = 63) and independent validation (n = 34) cohorts, although performance of all models were overall modest. CONCLUSIONS: We identify clinical and genomic features associated with rapid relapse TNBC for further study of this aggressive TNBC subset.

Modeling clonal structure over narrow time frames via circulating tumor DNA in metastatic breast cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) offers minimally invasive means to repeatedly interrogate tumor genomes, providing opportunities to monitor clonal dynamics induced by metastasis and therapeutic selective pressures. In metastatic cancers, ctDNA profiling allows for simultaneous analysis of both local and distant sites of recurrence. Despite the promise of ctDNA sampling, its utility in real-time genetic monitoring remains largely unexplored. METHODS: In this exploratory analysis, we characterize high-frequency ctDNA sample series collected over narrow time frames from seven patients with metastatic triple-negative breast cancer, each undergoing treatment with Cabozantinib, a multi-tyrosine kinase inhibitor (NCT01738438, https://clinicaltrials.gov/ct2/show/NCT01738438 ). Applying orthogonal whole exome sequencing, ultra-low pass whole genome sequencing, and 396-gene targeted panel sequencing, we analyzed 42 plasma-derived ctDNA libraries, representing 4-8 samples per patient with 6-42 days between samples. Integrating tumor fraction, copy number, and somatic variant information, we model tumor clonal dynamics, predict neoantigens, and evaluate consistency of genomic information from orthogonal assays. RESULTS: We measured considerable variation in ctDNA tumor faction in each patient, often conflicting with RECIST imaging response metrics. In orthogonal sequencing, we found high concordance between targeted panel and whole exome sequencing in both variant detection and variant allele frequency estimation (specificity = 95.5%, VAF correlation, r = 0.949), Copy number remained generally stable, despite resolution limitations posed by low tumor fraction. Through modeling, we inferred and tracked distinct clonal populations specific to each patient and built phylogenetic trees revealing alterations in hallmark breast cancer drivers, including TP53, PIK3CA, CDK4, and PTEN. Our modeling revealed varied responses to therapy, with some individuals displaying stable clonal profiles, while others showed signs of substantial expansion or reduction in prevalence, with characteristic alterations of varied literature annotation in relation to the study drug. Finally, we predicted and tracked neoantigen-producing alterations across time, exposing translationally relevant detection patterns. CONCLUSIONS: Despite technical challenges arising from low tumor content, metastatic ctDNA monitoring can aid our understanding of response and progression, while minimizing patient risk and discomfort. In this study, we demonstrate the potential for high-frequency monitoring of evolving genomic features, providing an important step toward scalable, translational genomics for clinical decision making.

Hematologists' barriers and enablers to screening and recruiting patients to a chimeric antigen receptor (CAR) T cell therapy trial: a theory-informed interview study.

BACKGROUND: Novel therapies often fail to reach the bedside due to low trial recruitment rates. Prior to conducting one of the first chimeric antigen receptor (CAR) T cell therapy trials in Canada, we used the Theoretical Domains Framework, a novel tool for identifying barriers and enablers to behavior change, to identify physician-related barriers and enablers to screening and recruiting patients for an early phase immunotherapy trial. METHODS: We conducted interviews with hematologists across Canada and used a directed content analysis to identify relevant domains reflecting the key factors that may affect screening and recruitment. RESULTS: In total, we interviewed 15 hematologists. Physicians expressed "cautious hope"; while expressing safety, feasibility, and screening criteria concerns, 14 out of 15 hematologists intended to screen for the trial (domains: knowledge, goals, beliefs about consequences, intentions). Physicians underscored the "challenging contexts," identifying resources, workload, forgetting, and patient wait times to receive CAR T cells as key practical barriers to screening (domains: environmental context and resources, memory, attention and decision-making, behavioral regulation). They also highlighted "variability in roles and procedures" that may lead to missed trial candidates (domain: social and professional role). Left unaddressed, these barriers may undermine trial recruitment. CONCLUSIONS: This study is among the first to use the Theoretical Domains Framework from the physician perspective to identify recruitment challenges to early phase trials and demonstrates the value of this approach for identifying barriers to screening and recruitment that may not otherwise have been elicited. This approach can optimize trial procedures and may serve to inform future promising early phase cancer therapy trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03765177 . Registered on December 5, 2018.

Navigating choice in the face of uncertainty: using a theory informed qualitative approach to identifying potential patient barriers and enablers to participating in an early phase chimeric antigen receptor T (CAR-T) cell therapy trial.

OBJECTIVES: Bench to bedside translation of groundbreaking treatments like chimeric antigen receptor T (CAR-T) cell therapy depends on patient participation in early phase trials. Unfortunately, many novel therapies fail to be adequately evaluated due to low recruitment rates, which slows patient access to emerging treatments. Using the Theoretical Domains Framework (TDF), we sought to identify potential patient barriers and enablers to participating in an early phase CAR-T cell therapy trial. DESIGN: We used qualitative semistructured interviews to identify potential barriers and enablers to patients' hypothetical participation in an early phase CAR-T cell therapy trial. We used the TDF and directed content analysis to identify relevant domains based on frequency, relevance and the presence of conflicting beliefs. PARTICIPANTS: Canadian adult patients diagnosed with haematological malignancies. RESULTS: In total, we interviewed 13 participants (8 women, 5 men). Participants ranged in age from 18 to 73 (median=56) and had been living with haematological cancer from a few months to several years. We found participants were unfamiliar with CAR-T cell therapy but wished to know more about treatment safety, efficacy and trial logistics (domains: knowledge, beliefs about consequences). They were motivated by altruistic considerations, though many prioritised personal health benefits despite recognising the goals (ie, establishing safety) of early phase clinical trials (domains: goals, intentions). Every participant valued receiving medical advice from their haematologists and oncologists, though some preferred impartial medical experts to inform their decision making (domain: social influences). Finally, participants indicated that improving access to financial and social supports would improve their trial participation experience (domain: environmental context and resources). CONCLUSION: Using the TDF allowed us to identify factors that might undermine participation to a CAR-T cell therapy trial and to optimise recruitment processes by considering patient perspectives to taking part in early phase trials.Trial regestration: NCT03765177; Pre-results.

Sociodemographic Factors Associated With Rapid Relapse in Triple-Negative Breast Cancer: A Multi-Institution Study.

BACKGROUND: Triple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. Our objective was to evaluate clinicopathologic and sociodemographic features associated with rrTNBC. METHODS: We included patients diagnosed with stage I-III TNBC in 1996 through 2012 who received chemotherapy at 1 of 10 academic cancer centers. rrTNBC was defined as a distant metastatic recurrence event or death ≤24 months after diagnosis. Features associated with rrTNBC were included in a multivariable logistic model upon which backward elimination was performed with a P<.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts. RESULTS: Among all patients with breast cancer treated at these centers, 3,016 fit the inclusion criteria. Training cohort (n=2,112) bivariable analyses identified disease stage, insurance type, age, body mass index, race, and income as being associated with rrTNBC (P<.10). In the final multivariable model, rrTNBC was significantly associated with higher disease stage (adjusted odds ratio for stage III vs I, 16.0; 95% CI, 9.8-26.2; P<.0001), Medicaid/indigent insurance, lower income (by 2000 US Census tract), and younger age at diagnosis. Model performance was consistent between the training and validation cohorts. In sensitivity analyses, insurance type, low income, and young age were associated with rrTNBC among patients with stage I/II but not stage III disease. When comparing rrTNBC versus late relapse (>24 months), we found that insurance type and young age remained significant. CONCLUSIONS: Timing of relapse in TNBC is associated with stage of disease and distinct sociodemographic features, including insurance type, income, and age at diagnosis.

Socioeconomic and Surgical Disparities are Associated with Rapid Relapse in Patients with Triple-Negative Breast Cancer.

BACKGROUND: A subset of triple-negative breast cancer (TNBC) is characterized by aggressive disease, rapid relapse, and mortality within 24 months of diagnosis, termed "rapid relapse" TNBC (rrTNBC). The objective of this study is to define the association between sociodemographic variables and surgical management among rrTNBC patients in the Surveillance, Epidemiology and End Results (SEER) Program. METHODS: TNBC patients diagnosed from January 1, 2010 to December 31, 2014 with local or regional disease were identified in SEER. Patients were stratified as rrTNBC, defined as disease specific mortality ≤ 24 months after diagnosis, and non-rrTNBC. Chi-squared tests, t tests, and multivariable logistic regression were used to assess the association of rapid relapse with sociodemographic variables and surgical management. RESULTS: The cohort included 8% (1378/17,369) rrTNBCs. A higher proportion of rrTNBC patients had no surgery (11.7%) compared with non-rrTNBC (2.6%). Omission of axillary staging among patients who had surgery was 6.2% rrTNBC versus 4.5% non-rrTNBC. Black race (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.05-1.43; p = 0.01; white ref), Medicaid or no insurance (Medicaid OR 1.53, 95% CI 1.31-1.79; p < 0.001; no insurance OR 1.74, 95% CI 1.31-2.32; p < 0.001; private ref), single status (OR 1.19, 95% CI 1.01-1.39; p = 0.03; married ref), no breast (OR 2.35, 95% CI 1.77-3.11; p < 0.001; mastectomy ref), and no axillary surgery (OR 1.44, 95% CI 1.13-1.83; p = 0.003 axillary surgery ref) were associated with rapid relapse. CONCLUSIONS: Medicaid or no insurance, single status, black race, and no surgery are associated with higher odds of rrTNBC in SEER. These results indicate an interplay between socioeconomic factors, clinical and genomic variables may be disproportionately contributing to worse outcomes among a subset of TNBC patients.

Association of Immunophenotype With Pathologic Complete Response to Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer: A Secondary Analysis of the BrighTNess Phase 3 Randomized Clinical Trial.

IMPORTANCE: Adding carboplatin to standard neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) likely benefits a subset of patients; however, determinants of benefit are poorly understood. OBJECTIVE: To define the association of molecular subtype, tumor proliferation, and immunophenotype with benefit of carboplatin added to NAC for patients with stages II to III TNBC. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of a phase 3, double-blind, randomized clinical trial (BrighTNess) that enrolled 634 women across 145 centers in 15 countries. Women with clinical stages II to III TNBC who had undergone pretreatment biopsy were eligible to participate. Whole transcriptome RNA sequencing was performed on the biopsy specimens. The prespecified end point was association of pathologic complete response (pCR) with gene expression-based molecular subtype, with secondary end points investigating established signatures (proliferation, immune) and exploratory analyses of immunophenotype. Data were collected from April 2014 to March 2016. The study analyses were performed from January 2018 to March 2019. INTERVENTIONS: Neoadjuvant chemotherapy with paclitaxel followed by doxorubicin and cyclophosphamide, or this same regimen with carboplatin or carboplatin plus veliparib. MAIN OUTCOMES AND MEASURES: Association of gene expression-based molecular subtype (PAM50 and TNBC subtypes) with pCR. RESULTS: Of the 634 women (median age, 51 [range, 22-78] years) enrolled in BrighTNess, 482 (76%) patients had evaluable RNA sequencing data, with similar baseline characteristics relative to the overall intention-to-treat population. Pathologic complete response was significantly more frequent in PAM50 basal-like vs nonbasal-like cancers overall (202 of 386 [52.3%] vs 34 of 96 [35.4%]; P = .003). Carboplatin benefit was not significantly different in basal-like vs nonbasal-like subgroups (P = .80 for interaction). In multivariable analysis, proliferation (hazard ratio, 0.36; 95% CI, 0.21-0.61; P < .001) and immune (hazard ratio, 0.62; 95% CI, 0.49-0.79; P < .001) signatures were independently associated with pCR. Tumors above the median for proliferation and immune signatures had the highest pCR rate (84 of 125; 67%), while those below the median for both signatures had the lowest pCR rate (42 of 125; 34%). Exploratory gene expression immune analyses suggested that tumors with higher inferred CD8+ T-cell infiltration may receive greater benefit with addition of carboplatin. CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, triple-negative breast cancer subtyping revealed high pCR rates in basal-like and immunomodulatory subsets. Analysis of biological processes related to basal-like and immunomodulatory phenotypes identified tumor cell proliferation and immune scores as independent factors associated with achieving pCR; the benefit of carboplatin on pCR was seen across all molecular subtypes. Further validation of immunophenotype with existing biomarkers may help to escalate or de-escalate therapy for patients with TNBC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02032277.

Barriers to and enablers of attendance at diabetic retinopathy screening experienced by immigrants to Canada from multiple cultural and linguistic minority groups.

AIM: To identify barriers to/enablers of attendance at eye screening among three groups of immigrantsto Canada from cultural/linguistic minority groups living with diabetes. METHODS: Using a patient-oriented research approach leveraging Diabetes Action Canada's patient engagement platform, we interviewed a purposeful sample of people with type 2 diabetes who had immigrated to Canada from: Pakistan (interviews in Urdu), China (interviews in Mandarin) and French-speaking African and Caribbean nations (interviews in French). We collected and analysed data based on the Theoretical Domains Framework covering key modifiable factors that may operate as barriers to or enablers of attending eye screening. We used directed content analysis to code barrier/enabler domains. Barriers/enablers were mapped to behaviour change techniques to inform future intervention development. RESULTS: We interviewed 39 people (13 per group). Many barriers/enablers were consistent across groups, including views about harms caused by screening itself, practical appointment issues including forgetting, screening costs, wait times and making/getting to an appointment, lack of awareness about retinopathy screening, language barriers, and family and clinical support. Group-specific barriers/enablers included a preference to return to one's country of birth for screening, the impact of winter, and preferences for alternative medicine. CONCLUSION: Our results can inform linguistic and culturally competent interventions to support immigrants living with diabetes in attending eye screening to prevent avoidable blindness.

Behavioral Determinants of Canadian Radiation Oncologists' Use of Single Fraction Palliative Radiation Therapy for Uncomplicated Bone Metastases.

BACKGROUND: A mainstay therapy for pain relief from uncomplicated bone metastases is external beam radiation therapy. Single fraction radiation therapy (SFRT) is more convenient and cost-effective, causes fewer acute side effects, and is equivalent to multiple fraction radiation therapy for pain relief. Despite these advantages, radiation oncologists seldom prescribe SFRT. PURPOSE: To identify the behavioral determinants to Canadian radiation oncologists' use of SFRT for uncomplicated bone metastases. METHODS AND MATERIALS: Semistructured interviews were conducted with 38 radiation oncologists from all 10 Canadian provinces. The interview guide and analysis were guided by the Theoretical Domains Framework (TDF). Transcripts were analyzed using a 5-phase thematic content analysis process: coding, generation of belief statements, generation of themes within TDF domains, generation of overarching themes, and classification of themes as barriers or facilitators to SFRT use, or as divergent (a barrier or facilitator depending on the participant). RESULTS: Thirteen overarching themes were identified of which 2 were barriers, 7 were facilitators, and 4 were divergent. The most commonly identified theme was the facilitator "most radiation oncologists are aware of evidence and guidelines on the use SFRT" (n = 38, 100%). The 3 next most reported themes (n = 37, 97.4% ) were (1) "radiation oncologists' use of SFRT can influence their colleagues" use of it (divergent), (2) experience with SFRT can increase its use (facilitator), and (3) SFRT is convenient for patients (facilitator). The most commonly identified barrier (n = 31, 81.6%) was "SFRT is associated with a higher risk of retreatment." CONCLUSIONS: Our use of the TDF to explore the behavioral determinants of Canadian radiation oncologists' use of SFRT for uncomplicated bone metastases identified a range of factors that are perceived to encourage and discourage its use. Our results will inform the design of future interventions to increase the use of SFRT.

Partnering with patients to get better outcomes with chimeric antigen receptor T-cell therapy: towards engagement of patients in early phase trials.

AIM: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol to assess a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). METHODS: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team's professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. RESULTS: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience. CONCLUSIONS: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future in order to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. TRIAL REGISTRATION: Affiliated with the development of NCT03765177.