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Background Poorly controlled diabetes is a predictor of chemotherapy induced peripheral neuropathy (CIPN) and hyperglycemia may mediate CIPN risk. We evaluated the association between hyperglycemia and CIPN development. Findings Methods: This was a secondary analysis of the CONTRoL trial, which randomized patients with Stage I-III breast cancer receiving taxane chemotherapy to cryotherapy, compression therapy, or placebo. CIPN data was obtained from the FACT-NTX survey which patients completed at baseline, week-12, and week-24. Hyperglycemia (glucose ≥ 140 mmol/L) was assessed using random glucose values obtained throughout trial duration. We included patients who completed FACT-NTX at baseline and week-12. Patients were divided into two groups based on CIPN development. For each group we calculated the proportion of patients with hyperglycemia and mean glucose values; 95% confidence intervals were constructed. Results Fifty-nine patients met inclusion criteria; 34 patients developed CIPN and 25 did not. Hyperglycemia occurred in 47.1% vs. 36.0% of patients who developed CIPN vs. those who did not ( p  = 0.56). Mean glucose was numerically but not significantly higher in patients with CIPN compared to those without at all timepoints, most notably at week-12 (132.2 mg/dL vs. 122.9 mg/dL p  = 0.47). Conclusions In this analysis, hyperglycemia affected almost half of patients with CIPN versus about a third of patients without CIPN. Patients with CIPN also had higher mean glucose levels compared to those without CIPN, though the differences were not significant. No conclusions can be drawn from these results and further research is needed to assess these trends in a larger prospective patient population.

BackgroundSurvival outcomes in metastatic breast cancer (MBC) have improved due to novel agents such as CDK4/6 inhibitors (CDK4/6i). Nevertheless, Black patients and patients with lower socioeconomic status (SES) continue to bear a disproportionate mortality burden.MethodsWe conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database (FHD). A dataset was constructed to include Black/African-American (Black/AA) and White patients with hormone receptor (HR)-positive, HER2-negative MBC. Outcomes included CDK4/6i use (overall and first-line), and rates of leukopenia, dose reduction, and time on treatment for first-line CDK4/6i. Multivariable logistic regression was used to evaluate factors associated with use and outcomes.ResultsA total of 6802 patients with MBC were included, of which 5187 (76.3%) received CDK4/6i. Of those, 3186 (61.4%) received CDK4/6i first-line. Overall, 86.7% of patients were categorized as White and 13.3% as Black/AA; 22.4% were > 75 years old; 12.6% were treated at an academic site; 3.3% had Medicaid insurance. In addition to advanced age and poorer performance status, lower use of CDK4/6i was associated with Black/AA vs White race (72.9% vs 76.8%; OR 0.83, 95% CI 0.70–0.99, p = 0.04) and Medicaid vs commercial insurance (69.6% vs 77.4%; OR: 0.68, 95% CI 0.49–0.95, p = 0.02). Odds of CDK4/6i use were twofold higher for patients treated at an academic center (p < 0.001). Rates of CDK4/6i-induced leukopenia and dose reductions did not differ significantly by race, insurance type, or treatment site. Time on CDK4/6i was significantly lower among Medicaid patients (395 days) than patients with commercial insurance (558 days) or Medicare (643 days) (p = 0.03).ConclusionThis analysis of real-world data suggests that Black race and lower SES are associated with decreased CDK4/6i use. However, among patients treated with CDK4/6i, subsequent toxicity outcomes are similar. Efforts to ensure access to these life-prolonging medications are warranted.

Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005-2013. Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA<100% versus CAA = 100% (ref), 2) CAA<80% versus CAA≥80% (ref) and 3) CAA<80% versus 80%≤CAA<100% versus CAA = 100%. Poor statin adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA<100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

BackgroundThe MA32 study investigated whether 5 years of metformin (versus placebo) improves invasive disease-free survival in early-stage breast cancer (BC). Non-adherence to endocrine therapy (ET) and medications for chronic conditions is common and increases with drug toxicity and polypharmacy. This secondary analysis evaluates rates and predictors of early discontinuation of metformin, placebo, and ET among participants with HR-positive BC.MethodsPatients with high-risk non-metastatic BC were randomized to 60 months of metformin (850 mg BID) or placebo BID. Patients were administered bottles of metformin/placebo every 180 days. Metformin/placebo adherence was defined as a bottle dispensed at month 48 or later. The ET adherence analysis included patients with HR-positive BC who received ET with start and stop date reported, with adherence defined as > 48 months of use. Associations of covariates with study drug and ET adherence were examined using multivariable models.ResultsAmong the 2521 HR-positive BC patients, 32.9% were non-adherent to study drug. Non-adherence was higher among patients on metformin vs placebo (37.1% vs 28.7%, p < 0.001). Reassuringly, ET discontinuation rates were similar between treatment arms (28.4% vs 28.0%, p = 0.86). Patients who were non-adherent to ET were more likely to discontinue study therapy (38.8% vs 30.1%, p < 0.0001). In a multivariable analysis, study drug non-adherence was increased with metformin vs placebo (OR: 1.50, 95% CI 1.25–1.80; p < 0.0001); non-adherence to ET (OR: 1.47, 95% CI 1.20–1.79, p < 0.0001); grade 1 or greater GI toxicity during the first 2 years; lower age; and higher body mass index.ConclusionWhile non-adherence was higher among patients on metformin, it was still considerable among patients on placebo. Reassuringly, treatment arm allocation did not impact ET adherence. Attention to global medication adherence is needed to improve BC and non-oncological outcomes in cancer survivors.Trial registrationClinicalTrials.gov: NCT01.

Background Compared to older adults with breast cancer (BC), adolescents and young adults (AYAs) develop more aggressive disease necessitating more intensive therapy with curative intent, which is disruptive to planned life trajectories. The burden of unmet needs among AYA BC survivors exists in two domains: (1) symptoms (e.g., sexual problems, anxiety, fatigue, stress, hot flashes) and (2) AYA concerns (e.g., fertility, genetics, relationships, economic attainment). Improved attention to concerns and symptoms may improve symptom management and quality of life. The Young, Empowered and Strong (YES) trial tests the efficacy of a 9-month, multicomponent digital health intervention that includes monthly assessments of prevalent symptoms, a chat room, and journal to engage and support AYAs with BC by providing tailored information, resources, and support outside of the clinical setting. Methods YES is a multicenter, randomized controlled trial across three academic institutions in the United States with 400 participants randomized to either the YES intervention or usual care arm. Inclusion criteria include biologically female; 15–39 years of age at diagnosis of stage 0-III BC; within 3 years of diagnosis; no known evidence of recurrence; no prior history of new malignancy since initial BC diagnosis; and ability to access medical records from treatment site. All participants complete REDCap surveys at baseline, and at 3, 6, and 9 months post-enrollment. The primary outcome is quality of life as measured by the Quality of Life in Adult Cancer Survivors Scale (QLACS), with changes from baseline to 6-months in QLACS scores, compared by arm. Secondary outcomes include patient reported AYA concerns/needs, emotional symptoms, general health, physical symptoms, and health behaviors, Discussion Study findings will provide valuable insight into the ability of the YES digital health intervention to address symptoms and concerns of AYA BC survivors and assist them to track and self-manage their own symptoms, concerns, and needs related to their cancer outside of the clinic. Trial registration Clinicaltrials.gov, NCT04906200, registered May 13, 2021.

Metformin, an inexpensive oral agent commonly used to treat type 2 diabetes, has been garnering increasing attention as a potential anti-cancer agent. Preclinical, epidemiologic, and clinical evidences suggest that metformin may reduce overall cancer risk and mortality, with specific effects in breast cancer. The extensive clinical experience with metformin, coupled with its known (and modest) toxicity, has allowed the traditional process of drug evaluation to be shortened. We review the rationale for a modified approach to evaluation and outline the key steps that will optimize development of this agent in breast cancer, including discussion of a Phase III adjuvant trial (NCIC MA.32) that has recently been initiated.

Major advances in early detection and therapy have significantly increased the survival of breast cancer patients. Unfortunately, most cancer therapies are known to carry a substantial risk of adverse long-term treatment-related effects. Little is known about patient susceptibility to severe side effects after chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes. Recent advances in genome-wide genotyping and sequencing technologies have supported the discoveries of a number of pharmacogenetic markers that predict response to chemotherapy. However, effectively implementing these pharmacogenetic markers in the clinic remains a major challenge. On the other hand, recent advances in proteomic technologies incorporating mass spectrometry (MS) for biomarker discovery show great promise to provide clinically relevant protein biomarkers. In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment. Based on the change in FACT-Ntx score from baseline to 12 month follow-up, we separated patients into two groups: those who had no change (Group 1, N = 9) and those who had a ≥20% worsening (Group 1, N = 8). MS-based proteomics technology was used to identify proteins present in serum exosomes to determine potential biomarkers. Mann-Whitney-Wilcoxon analysis was applied and maximum FDR was controlled at 20%. From the serum exosomes derived from this cohort, we identified over 700 proteins known to be in different subcellular locations and have different functions. Statistical analysis revealed a 12-protein signature that resulted in a distinct separation between baseline serum samples of both groups (q<0.2) suggesting that the baseline samples can predict subsequent neurotoxicity. These toxicity-associated biomarkers can be further validated in larger retrospective cohorts for their utility in identifying patients at high risk for CIPN.

Objectives There is limited guidance on how to effectively educate cancer survivors to adopt and maintain specific diet and physical activity recommendations, especially among underserved and under-resourced populations. Here, the objective is to present the development of a behavioral and theoretically-based multi-modal diet and physical activity intervention program for Hispanic/Latina breast cancer survivors, Mi Vida Saludable (My Healthy Life). Methods The development process was based on the 6 steps of the Nutrition Education DESIGN Procedure: (1). Decide behaviors; (2). Explore determinants; (3). Select theory-based model; (4). Indicate objectives; (5). Generate plans; and (6). Nail down evaluation. The theoretical framework for the intervention is Social Cognitive Theory. Results The resulting behavioral intervention consists of 2 components. The first component is in-person group education consisting of 4 lessons over 1 month. Each 4-hour group lesson includes a hands-on cooking component, a physical activity component, and facilitator-led nutrition education and discussion, with 2 field trips to a local grocery store and farmers’ market. The second component is an e-Health program that includes weekly text messages, biweekly emailed newsletters, and ongoing website access. Conclusion The systematic DESIGN Procedure provided practical guidance for developing a behaviorally-focused, theory-based, and culturally sensitive program that addresses both dietary and physical activity behaviors for delivery both in-person education and through eHealth. The Procedure may be useful for developing other behaviorally focused and theory-based interventions.

Abstract BACKGROUND There is growing recognition that perioperative complication rates are similar between hospitals, but mortality rates are lower at high-volume centers. This may be due to differences in the ability to rescue patients from major complications. OBJECTIVE To examine the relationship between hospital caseload and failure to rescue from complications following resection of intracranial neoplasms. METHODS We identified adults in the Nationwide Inpatient Sample diagnosed with glioma, meningioma, brain metastasis, or acoustic neuroma, who underwent surgical resection between 1998 and 2010. We stratified hospitals by low, intermediate, and high surgical volume tertiles and calculated failure to rescue rates (mortality in patients after a major complication). RESULTS A total of 550 054 patients were analyzed. Overall risk-adjusted complication rates were comparable between low- and medium-volume centers, and slightly lower at high-volume centers (15.3% [15.2, 15.5] vs 15.7% [15.5, 15.9] vs 14.3% [14.1, 14.6]). Risk-adjusted mortality decreased with increasing hospital surgical volume (10.3% [10.2, 10.5] vs 9.0% [8.9, 9.1] vs 7.1% [7.0, 7.2]). The overall risk-adjusted failure to rescue rate also decreased with increasing surgical volume (26.9% [26.3, 27.4] vs 24.8% [24.3, 25.3] vs 20.9% [20.5, 21.5]). CONCLUSION While complication rates were similar between high-volume and low-volume hospitals following craniotomy for tumor, mortality rates were substantially lower at high-volume centers. This appears to be due to the ability of high-volume hospitals to rescue patients from major perioperative complications.

Background The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR). Methods In this retrospective evaluation of 105 patients with stage II–III breast cancer, oxy-hemoglobin ( ctO 2 Hb ) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2–3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO 2 Hb changes across chemotherapy when corrected for pCR status, age, and BMI. Results Patients who achieved pCR to NAC had an overall decrease of 3.88 μM for ctO 2 Hb (95% CI, 1.39 to 6.37 μM), p  = .004, after 2–3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 μM (95% CI, − 1.30 to 1.58 μM), p  > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO 2 Hb levels with BMI and age. Conclusions This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2–3 weeks of chemotherapy.