Photothermally reinforced chemodynamic therapy in the treatment of osteosarcoma by polydopamine-modified, copper peroxide loaded ZIF8 nanoparticles.

Chemodynamic therapy (CDT) has played an important role in osteosarcoma (OS) treatment. However, the insufficient content of endogenous H2O2 and high expression of glutathione (GSH) in tumor tissues limit the antitumor efficacy of CDT. In this work, we developed polydopamine (PDA) coated and CuO2 NPs loaded ZIF8 nanoparticles (CuO2@ZIF8@PDA NPs) for thermally reinforced CDT treatment of OS. The CuO2@ZIF8@PDA NPs exhibited excellent stability in neutral solutions while degraded in weakly acidic environments to generate hydrogen peroxide (H2O2) and Cu2+. Cu2+ consumes GSH in tumor tissues to generate Cu+. Both Cu2+ and Cu+ catalyzed the decomposition of H2O2, triggering a Fenton-like reaction to produce hydroxyl radicals (•OH). The PDA coating endowed the nanosystem with photothermal conversion capabilities under near-infrared laser irradiation, further promoting the generation of •OH, and inducing tumor cell death. In vitro experiments demonstrated that CuO2@ZIF8@PDA NPs exhibited significant toxicity towards K7M2 cells while remaining non-toxic to normal cells. In vivo studies revealed that under 808 nm laser irradiation, CuO2@ZIF8@PDA NPs exhibited stronger killing ability against K7M2 cells than CuO2@ZIF8@PDA NPs alone. This system, which combines GSH depletion, intratumoral H2O2 self-generation, and photothermally enhanced CDT, holds great promise for playing a pivotal role in the treatment of osteosarcoma.

Palbociclib plus aromatase inhibitors in patients with metastatic breast cancer and cardiovascular diseases: real-world effectiveness.

BACKGROUND: Patients with cardiovascular disease (CVD) comorbidities are often excluded from participating in breast cancer clinical trials. Consequently, data to inform treatment decisions for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and CVD are limited. OBJECTIVE: We compared the effectiveness of first-line palbociclib plus an aromatase inhibitor (AI) vs an AI alone and evaluated palbociclib treatment patterns in patients with HR+/HER2- mBC and CVD in routine clinical practice. METHODS: Data from the Flatiron Health Analytic Database were captured for patients with HR+/HER2- mBC and CVD who initiated first-line treatment with palbociclib plus an AI or an AI alone between February 2015 and March 2020 (data cutoff: September 30, 2020). Overall survival (OS), real-world progression-free survival (PFS), and treatment patterns were evaluated. RESULTS: Of the 469 patients with identifiable CVD, 160 received palbociclib plus an AI, and 309 received an AI alone. After stabilized inverse probability treatment weighting, both median OS (40.7 vs 26.5 months; hazard ratio [HR], 0.732 [95% CI, 0.537-0.997]; P = .048) and median real-world PFS (20.0 vs 12.5 months; HR, 0.679 [95% CI, 0.512-0.900]; P = .007) were significantly prolonged in patients treated with palbociclib plus an AI vs an AI alone. Among patients with a documented palbociclib starting dose, 78.5% started palbociclib at 125 mg/day, and 38.6% experienced dose adjustment. CONCLUSIONS: In this real-world analysis, first-line palbociclib plus an AI was associated with improved effectiveness compared with an AI alone in patients with HR+/HER2- mBC and CVD. TRIAL REGISTRATION: NCT05361655 (ClinicalTrials.gov).

Bidirectional associations between short sleep duration, insomnia symptoms, and psychotic-like experiences in adolescents.

This study investigates the prospective associations between short sleep duration, insomnia symptoms, and psychotic-like experiences (PLEs) in a large sample of Chinese adolescents. This study utilized a three-timepoint repeated cross-sectional survey with two nested longitudinal subsamples. A total of 17,722 adolescents were assessed at baseline (April 21 to May 12, 2021) and six months later (December 17 to 26, 2021). Out of these, 15,694 adolescents provided complete responses to the questions at baseline and one year later (May 17 - June 6, 2022). A self-administered questionnaire was used to measure sample characteristics (at baseline), sleep duration, insomnia symptoms, and PLEs (at each assessment), and negative life events (at two follow-ups). Baseline short sleep duration and insomnia symptoms predicted frequent PLEs at both follow-up assessments. Additionally, baseline frequent PLEs also predicted insomnia symptoms at six months and one year later. However, when controlling for confounders, PLEs at baseline only predicted short sleep duration at six months, and not at one year. This study reveals bidirectional prospective relationships between short sleep duration, insomnia symptoms, and PLEs, even after controlling for covariates. Therefore, it is crucial to assess both sleep patterns and PLEs in order to promote optimal sleep and mental health among adolescents.

Psychometric properties of the Youth Self-rated Insomnia Scale (YSIS) in adolescent psychiatric patients.

The 8-item Youth Self-rated Insomnia Scale (YSIS) was developed to assess insomnia severity in the past month among youths. The YSIS has satisfactory psychometric properties in the general adolescent population. This study examined psychometric properties of the YSIS in a large sample of adolescent psychiatric patients. A total of 536 patients aged 10-19 years were consecutively recruited from the outpatient department of Shandong Mental Health Center between December 2021 and March 2022. Patients completed a structured questionnaire consisting of the YSIS scale and questions about sleep duration, nightmares, psychiatric history, depression, psychiatric and sleep medications, and demographics. Patients were diagnosed following the ICD-10 criteria. Of the participants, the mean age was 15.30 years (SD = 1.95), 61.0% were female, 60.9% were diagnosed with mood disorders, 65.7% were on antidepressants, and 49.0% were on anxiolytics or hypnotics. The mean YSIS score was 22.6 (SD = 8.07). Coefficient omega was 0.84. Exploratory factor analysis revealed one factor and two correlated residuals. The YSIS scores were significantly correlated with depression scores (r = 0.68) and significantly increased with sleep onset latency, short sleep duration, nightmare frequency, and sleep medication use. The YSIS demonstrated satisfactory internal consistency reliability, construct validity, and criteria-related validity in adolescent psychiatric patients. The YSIS appears to be a reliable and valid scale for measuring insomnia severity in adolescent psychiatric patients.

Prolonging the lives of African-Americans with metastatic breast cancer by adding palbociclib to an aromatase inhibitor in routine clinical practice: a plain language summary of a real-world database study.

WHAT IS THIS SUMMARY ABOUT?: This summary is about a study that was published in the medical journal The Oncologist in July 2023. The combination of palbociclib with an aromatase inhibitor (AI) was approved by the FDA in 2015 as a treatment for people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, the effectiveness of palbociclib in African-Americans with MBC is not well studied. The goal of this study was to find out whether adding palbociclib to an AI helped African-Americans with HR+/HER2- MBC live longer. WHAT ARE THE KEY TAKEAWAYS?: This study used de-identified medical information from the Flatiron Database. This database contains healthcare information on people with cancer treated by doctors in the United States but personal information is removed to maintain privacy. Medical information for people who received certain treatments in routine clinical practice or real-world setting was included in the study.This study showed that in the real-world setting, African-Americans with HR+/HER2- MBC lived longer when receiving palbociclib with an AI than with an AI alone. Also, the study showed that African-Americans treated with palbociclib plus an AI lived longer without their cancer getting worse than those treated with an AI alone. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: These results support the use of palbociclib with an AI as a first treatment for African-Americans with HR+/HER2- MBC.Clinical Trial Registration: NCT05361655 (ClinicalTrials.gov).

Effectiveness of palbociclib plus an aromatase inhibitor in African Americans with metastatic breast cancer in routine clinical practice: a plain language summary.

Treatment outcomes in older patients with metastatic breast cancer receiving palbociclib plus an aromatase inhibitor: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary describes an article published in the medical journal Frontiers in Oncology in September 2023. The article reports results from a study that looked at breast cancer treatments for older patients aged 75 years or older. The study focused on a type of cancer called HR+/HER2- metastatic breast cancer. HR+/HER2- stands for hormone receptorpositive/human epidermal growth factor receptor 2-negative. This study evaluated whether older patients with this type of cancer benefited from the combination of two medicines - palbociclib and an aromatase inhibitor - compared with taking an aromatase inhibitor alone. HOW WAS THE STUDY IN THIS SUMMARY CARRIED OUT?: The Flatiron database contains medical records for people with cancer in the US. This study used deidentified health care information from this database. 'Deidentified' means that all information that could identify an individual was removed to protect individuals' privacy. People in this study received treatment in routine care and not in a clinical trial. WHAT DO THE RESULTS MEAN?: Older patients who took palbociclib plus an aromatase inhibitor lived longer than those who took an aromatase inhibitor alone. Older patients who took palbociclib plus an aromatase inhibitor also lived longer without their cancer getting worse and started chemotherapy later than those who took an aromatase inhibitor alone. These results support using palbociclib plus an aromatase inhibitor as the first treatment for patients aged 75 years or older with HR+/HER2- metastatic breast cancer.

This study evaluated outcomes in elderly patients with metastatic breast cancer treated in routine care. Overall, patients who took palbociclib plus an aromatase inhibitor (AI) lived longer, and lived longer without their cancer getting worse, than those who took an AI alone.

Silencing FUT4 Inhibits the Progression of Osteosarcoma through Activation of FOXO1.

BACKGROUND: It has been reported that inhibition of Fucosyltransferase4 (FUT4) to activate Forkhead box O1 (FOXO1) can lead to apoptosis of cancer cells, however, the mechanism in osteosarcoma is still unclear. OBJECTIVE: To explore the biological significance of the connection between FUT4 and FOXO1 in osteosarcoma growth. METHODS: In vitro tests were conducted using the human osteoblast cell line and the osteosarcoma cell lines. QRT-PCR assay as well as western blot assay were used to ascertain the relative expression levels of FUT4 and FOXO1 in the cells. By using the CCK-8 assay, colony assay, EDU assay, wound healing assay and Transwell assay, osteosarcoma cells' ability to proliferate, migrate and invade were examined in relation to si- FUT4. TUNEL test was used to evaluate Si-impact FUT4's on KHOS and U2OS apoptosis in osteosarcoma cells. Western blot assay was used to identify the expression of proliferative, migrating and apoptosis-related protein markers in osteosarcoma cells KHOS and U2OS and the expression of important proteins in the Wnt/ ß-catenin signaling pathway. RESULTS: In comparison with osteoblasts, osteosarcoma cells expressed more FUT4. The osteosarcoma cells' capacities to proliferate, invade, and migrate were markedly inhibited by the inhibition of FUT4 expression, which also increased osteosarcoma cell apoptosis. The Wnt/ß-catenin signaling pathway was blocked by upregulating FOXO1 expression, which was in turn inhibited by inhibiting FUT4 expression. CONCLUSION: Osteosarcoma cells express more FUT4. The Wnt/ß-catenin signaling pathway has a significant effect on osteosarcoma cell death, and inhibition of FUT4 expression may target FOXO1 activation to decrease osteosarcoma cells' ability to proliferate, invade, and migrate.

Bidirectional associations between sleep problems and suicidal thought/attempt in adolescents: A 3-wave data path analysis.

PURPOSE: This longitudinal data analysis examined the bidirectional relationships between sleep problems and suicidal thought (ST)/attempt (SA) in a large sample of Chinese adolescents. METHODS: A total of 6995 adolescents (mean age = 14.86 years and 51.4% males) participated in a 3-wave longitudinal study of behavior and health in Shandong, China. A self-administered questionnaire and standardized scales were used to assess ST, SA, sleep duration, insomnia, daytime sleepiness, and behavioral/emotional problems in 2015 (T1), 1 year later (T2), and 2 years later (T3). Path analyses were performed without and with adjustment for covariates, including gender, grade level, chronic diseases, cigarette smoking, alcohol use, anxiety/depressive symptoms, paternal education, and family economic status. RESULTS: The prevalence rates of short sleep (<7 h/night), insomnia symptoms, and daytime sleepiness were 46.9-58.8%, 16.0-19.4%, and 25.1-25.3% at T1, T2, and T3, respectively. The rates of past-year ST and SA were 9.1-12.4% and 1.6-2.4% at T1, T2, and T3, respectively. Path analyses showed that short sleep, insomnia, and daytime sleepiness predicted subsequent ST, and vice versa. Daytime sleepiness and SA predicted each other 1 year later. Sleep problems and ST/SA in the previous year significantly predicted themselves in the follow-up year. STUDY LIMITATION: All data were based on self-report. CONCLUSION: Short sleep, insomnia, and daytime sleepiness all had bidirectional relationships with ST. Daytime sleepiness and SA were bidirectionally linked. Our findings suggest that interventions should be taken for both night sleep disturbances and daytime sleepiness to prevent suicide. Adverse sleep outcomes in suicidal adolescents should be assessed, which can in turn increase suicide risk.

Real-world treatment patterns for palbociclib plus an aromatase inhibitor, or an aromatase inhibitor alone, for patients with metastatic breast cancer in the Flatiron Database.

There are limited real-world comparative effectiveness data for palbociclib plus an aromatase inhibitor (AI) as a first-line (1L) treatment examining endpoints that require long term follow-up and post 1L progression. The Flatiron Health Analytic Database was used to characterize treatment and dosing patterns in patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) receiving palbociclib plus an AI vs an AI alone in routine US clinical practice. In addition, time to chemotherapy (TTC) and real-world progression-free survival (rwPFS) when combining 1L and second-line of therapy (rwPFS2) were assessed. Of 1324 patients who received palbociclib plus an AI between February 3, 2015 and March 31, 2020, 1110 (83.8%) started palbociclib at the recommended 125 mg/day dose. After stabilized inverse probability treatment-weighting (sIPTW), median TTC in patients treated with palbociclib plus an AI and AI alone was 37.4 months (95% confidence interval [CI], 33.7-40.7) and 29.2 months (95% CI, 26.8-33.5), respectively (hazard ratio [HR] = 0.77 [95% CI, 0.69-0.86], P < .0001); median rwPFS2 was 32.6 months (95% CI, 29.4-35.2) and 20.7 months (95% CI, 18.9-22.6), respectively (HR = 0.62 [95% CI, 0.54-0.70], P < .0001). Sensitivity analyses with propensity score matching showed similar results to sIPTW analyses. Results from this large real-world study examining additional effectiveness outcomes beyond 1L rwPFS and overall survival support the use of palbociclib plus an AI as a 1L treatment for patients with HR+/HER2- mBC.

Life stress and suicidality mediated by insomnia and depressive symptoms in adolescents: a three-wave longitudinal study.

STUDY OBJECTIVES: Little empirical work has investigated the associations between life stress (LS), insomnia, depression, and suicidality in multi-wave longitudinal studies. With three waves of data collection 1-year apart, this longitudinal study with a large sample of adolescents examined the predicting effects of LS on suicidality 1-year later and 2 years later and the mediating roles of insomnia and depression in the LS-suicidality link. METHODS: A total of 6995 adolescents (mean age = 14.86 years, 51.4% male) participated in a three-wave longitudinal study of behavior and health in Shandong, China. A self-administered structured questionnaire and standardized scales were used to assess suicidality (including suicidal thought [ST], suicide plan [SP], and suicide attempt [SA]), LS, insomnia, and depression in 2015 (T1), 1-year later (T2), and 2 years later (T3). Mediation effects were examined with path models. RESULTS: The overall prevalence rates of past-year suicidality were 13.4% at T1, 10.0% at T2, and 9.5% at T3, respectively. The prevalence rates of suicidality across T1-T3 significantly increased with elevated levels of baseline LS, insomnia, and depression (p < .001). Path models indicated that the relationship between baseline LS and suicidal ideation (i.e., ST/SP) 2 years later was significantly mediated by both insomnia and depression. Depression was also a significant mediator between LS and SA. CONCLUSIONS: LS is a significant predictor of suicidality 1-2 years later in adolescents. Depression mediates the association between LS and suicidal ideation and suicide attempt while insomnia appears to be a mediator for suicidal ideation rather than suicide attempt.

Lower Socioeconomic Status, Psychological Distress, and Self-reported Hypertension: A Longitudinal Moderated Mediation Analysis.

BACKGROUND: Lower socioeconomic status (SES) has been associated with hypertension; however, the mediators and moderators of this association remain understudied. We examined the mediation effect of psychological distress on the link between lower SES and self-reported hypertension and the racial and sex moderation effects. METHODS: We analyzed the data collected from 2009 to 2019 among adults from the Panel Study of Income Dynamics (PSID). Lower SES was defined as one of 3 indicators: education ≤12 years, unemployed, or individual annual income <$27,800. Psychological distress was assessed using the Kessler K6 scale. Cox proportional hazard regression was conducted. Mediation analyses were performed using the PROCESS macro. RESULTS: In the sample of heads of family who did not have self-reported hypertension in 2009 (N = 6,214), the mean age was 41 years, 30.6% were female, 32.9% were African American. The cumulative incidence of self-reported hypertension was 29.8% between 2009 and 2019. Cox proportional hazard regression analysis showed that after controlling for covariates, lower SES (score > 0 vs. score = 0) was associated with self-reported hypertension (hazard ratio = 1.27, 95% confidence interval = 1.14-1.42). SES had indirect effect on self-reported hypertension through psychological distress and the indirect effect (0.02 in females, 0.01 in males, P < 0.05) was moderated by sex but not by race. CONCLUSIONS: The association of SES and self-reported hypertension was mediated by psychological distress and sex moderated the mediation effect. Interventions focused on reducing contributors to SES and psychological stress should be considered to reduce hypertension risk.

Starting a Romantic Relationship, Breakups, and Sleep: A Longitudinal Study of Chinese Adolescents.

BACKGROUND: Epidemiological data on the association between romantic experiences and sleep in adolescents are limited. This study examined the associations of starting a romantic relationship (SRR) and romantic breakups with insomnia symptoms and sleep duration in adolescents. METHODS: A total of 7,072 Chinese adolescents were surveyed in November-December 2015 and 1 year later. A self-administered questionnaire was used to assess SRR, romantic breakups, sleep duration, insomnia symptoms, depressive symptoms, substance use, and demographics. RESULTS: The mean age of the sample was 14.58 (SD = 1.46) years and half were female. SRR only, breakups only, and both (SRR + breakups) in the past year were reported by 7.0%, 8.4%, and 15.4% of the sample, respectively. At the baseline and 1-year follow-up, 15.2% and 14.7% of the sample had insomnia symptoms and 47.7% and 42.1% reported short sleep duration (<7 h/night), respectively. After adjusting for depressive symptoms, substance use, and demographics, SRR and breakups were significantly associated with 35-45% increased odds of insomnia symptoms at baseline. SRR + breakups were significantly associated with short sleep duration (OR = 1.28, 95%CI = 1.05-1.56). SRR (OR = 1.61, 95%CI = 1.16-2.23) and breakups (OR = 1.43, 95%CI = 1.04-1.96) were significantly associated with increased odds of incident insomnia symptoms at 1-year follow-up. These associations were stronger in younger adolescents (<15 years) than in older adolescents (≥15 years), especially in girls. CONCLUSIONS: The findings suggest that SRR and breakups are associated with insomnia symptoms and short sleep duration, underscoring the importance of romantic relationships education and management of romantic stress for healthy sleep especially in early adolescent girls.

Palbociclib Combined with an Aromatase Inhibitor in Patients with Breast Cancer with Lung or Liver Metastases in US Clinical Practice.

A cyclin-dependent kinase 4/6 inhibitor combined with endocrine therapy is the standard of care for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC), but real-world effectiveness data for patients with lung or liver metastases are limited. This retrospective study included data from the US Flatiron Health database of patients with HR+/HER2- mBC and lung or liver metastases treated with first-line palbociclib (PAL) plus an aromatase inhibitor (AI) or an AI alone in routine clinical practice. Overall survival (OS) and real-world progression-free survival (rwPFS) were assessed. A total of 891 patients were included (622 with lung metastasis, 376 with liver metastasis, and 107 with both lung and liver metastasis). After stabilized inverse probability of treatment weighting to balance patient characteristics, PAL + AI versus AI alone was associated with significantly prolonged OS (HR = 0.62; p < 0.001) and rwPFS (HR = 0.55; p < 0.001) in patients with lung metastases and numerically longer OS (HR = 0.73; p = 0.056) and significantly longer rwPFS (HR = 0.57, p < 0.001) for those with liver metastases. Overall, PAL + AI versus AI alone was associated with prolonged OS and rwPFS in routine clinical practice, supporting the use of first-line PAL + AI for patients with HR+/HER2- mBC with lung and/or liver metastases.

Prevalence and Associated Factors of Premenstrual Syndrome in Chinese Adolescent Girls.

Epidemiological data on premenstrual syndrome (PMS) in Chinese adolescents are limited. This study reported the prevalence and associated factors of PMS in a large sample of Chinese adolescents. A total of 5099 adolescent girls who had menarche participated in the baseline survey of Shandong Adolescent Behavior and Health Cohort study in Shandong, China. A self-administered questionnaire was used to ask about PMS, age at menarche, menstrual cycle interval, menstrual flow length, menstrual regularity, period pain, body weight and height, trait anger, stressful life events, and demographics. The mean age of the sample was 15.19 years (SD = 1.32). The overall prevalence of PMS was 24.6%. The prevalence rates of PMS-anxiety, PMS-water retention, PMS-craving, and PMS-depression were 18.9%, 4.0%, 7.9%, and 11.5%, respectively. The most common symptoms were premenstrual irritability (54%) and fatigue (52.5%). Stepwise logistic regression showed that high levels of life stress (OR 2.26), high levels of trait anger (OR 4.65), alcohol consumption (OR 1.28), menstrual cycle interval ≤ 24 days (OR 1.45), and mild (OR 1.50), moderate (OR 2.57) or severe period pain (OR 4.84) were all significantly associated with increased likelihood of PMS. In conclusion, approximately 1 in 4 Chinese adolescent girls suffered from PMS. Multiple psychosocial and menstrual factors were associated with PMS. Further research is needed to understand developmental changes of PMS and its long-term impacts on psychosocial wellbeing in Chinese adolescent girls.

Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older.

Background: Elderly patients are generally underrepresented in oncology clinical trials; therefore, real-world data are needed to inform clinical management of elderly patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). This subanalysis of the P-REALITY X study (NCT05361655) evaluated palbociclib treatment patterns and comparative effectiveness of palbociclib plus an aromatase inhibitor (AI) versus an AI alone among patients with HR+/HER2- mBC aged ≥ 75 years treated in routine clinical practice in the United States. Methods: This retrospective observational cohort study used electronic health records from the Flatiron Health Analytic Database. Palbociclib treatment patterns, overall survival (OS), real-world progression-free survival (rwPFS), and time to chemotherapy (TTC) were evaluated. Three methods were used for comparative analyses: (1) an unadjusted analysis, (2) stabilized inverse probability treatment weighting (sIPTW; primary analysis), and (3) propensity score matching (PSM; sensitivity analysis). Results: A total of 961 patients aged ≥ 75 years with HR+/HER2- mBC were identified who started palbociclib plus an AI (n = 313) or an AI alone (n = 648) as first-line (1L) therapy between February 2015 and March 2020 (data cut-off: September 30, 2020). Among patients in the palbociclib plus an AI group with a documented palbociclib starting dose (n = 306), approximately 75% started palbociclib at 125 mg/day, and approximately 40% experienced dose adjustment. After sIPTW, patients treated with palbociclib plus an AI versus an AI alone had significantly improved OS (median of 43.0 vs. 32.4 months; hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.51-0.84]; P = 0.0007), rwPFS (median of 20.0 vs. 15.0 months; HR, 0.72 (0.59-0.89); P = 0.0021), and TTC (median of 40.2 vs. 27.4 months; HR, 0.69 [0.55-0.87]; P = 0.0014). These significant improvements in OS, rwPFS, and TTC remained consistent in the unadjusted analysis and after PSM. Conclusion: This real-world comparative analysis demonstrated that 1L palbociclib plus an AI is associated with improved effectiveness compared with an AI alone among patients with HR+/HER2- mBC aged ≥ 75 years. These findings support palbociclib plus an AI as a standard-of-care 1L treatment for elderly patients with HR+/HER2- mBC.

Real-World Effectiveness of Palbociclib Plus Aromatase Inhibitors in African American Patients With Metastatic Breast Cancer.

BACKGROUND: Disparities in survival and clinical outcomes between African American and White patients with breast cancer (BC) are well documented, but African American patients have not been well represented in randomized clinical trials of CDK4/6 inhibitors. Real-world studies can provide evidence for effective treatment strategies for underreported patient populations. PATIENTS AND METHODS: This retrospective analysis of African American patients with HR+/HER2- metastatic breast cancer (mBC) from the Flatiron Health longitudinal database evaluated treatments for patients with BC in routine clinical practice in the US. Patients initiated first-line therapy with palbociclib plus an aromatase inhibitor (AI) or AI alone between February 2015 and March 2020. Outcomes assessed included overall survival (OS) and real-world progression-free survival (rwPFS) until September 2020. RESULTS: Of 270 eligible patients, 127 (median age 64 years) were treated with palbociclib + AI, and 143 (median age 68 years) were treated with an AI. Median follow-up was 24.0 months for palbociclib + AI and 18.2 months for AI-treated patients. Median OS was not reached (NR; 95% CI, 38.2-NR) in the palbociclib + AI group versus 28.2 months (95% CI, 19.2-52.8) in the AI group (adjusted HR, 0.56; 95% CI, 0.36-0.89; P = .013). Median rwPFS was 18.0 months (95% CI, 12.4-26.7) in the palbociclib + AI group and 10.5 months (95% CI, 7.0-13.4) in the AI group (adjusted HR, 0.74; 95% CI, 0.47-1.17; P = .199). CONCLUSION: This comparative analysis of palbociclib + AI versus AI alone indicates that palbociclib combined with endocrine therapy in the first line is associated with improved effectiveness for African American patients with HR+/HER2- mBC in real-world settings. TRIAL NUMBER: NCT05361655.

Psychosocial Wellbeing among Patients with Breast Cancer during COVID-19.

The impact of coronavirus disease 2019 (COVID-19) on the wellbeing of breast cancer (BC) patients is not well understood. This study described psychosocial problems among these patients in the United States (US) during the COVID-19 pandemic. Data were collected from BC patients via an online self-report survey between 30 March-6 July 2021 to assess the prevalence of COVID-19 diagnosis history and potential depression, health-related quality of life, COVID-related stress, and financial toxicity. Patients with early-stage (eBC) and metastatic (mBC) disease were compared. Of 669 patients included in the analysis, the prevalence of COVID-19 diagnosis history (10.9% versus 7.7%) and potential depression (33.7% versus 28.3%) were higher in mBC than eBC patients. Patients with eBC (versus mBC) had higher scores on nearly all Functional Assessment of Cancer Therapy-Breast scales (all, p < 0.001). For the Psychological Impact of Cancer subscales measuring negative coping strategies, the emotional distress score was the highest (9.1 ± 1.8) in the overall sample. Comprehensive Score for Financial Toxicity scores were higher in eBC than in mBC patients (24.2 ± 11.3 vs. 21.3 ± 10.2, p < 0.001). Overall, the COVID-19-related stress score was highest for danger/contamination fears (8.2 ± 5.6). In conclusion, impairments to psychosocial wellbeing among patients during the pandemic were observed, particularly financial toxicity and poor mental health and emotional functioning, with greater problems among mBC patients.

Palbociclib Adherence and Persistence in Patients with Hormone Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer.

Purpose: To assess adherence and persistence with palbociclib therapy in patients with HR+/HER2- metastatic breast cancer (mBC) in a US real-world setting. Methods: This retrospective study evaluated palbociclib dosing, adherence, and persistence using commercial and Medicare Advantage with Part D claims data from the Optum Research Database. Adult patients with mBC who had continuous enrollment 12 months prior to mBC diagnosis and initiated first-line palbociclib with aromatase inhibitor (AI) or fulvestrant between 02/03/2015 and 12/31/2019 were included. Demographic and clinical characteristics, palbociclib dosing and dose changes, adherence (medication possession ratio [MPR]), and persistence were measured. Adjusted logistic and Cox regression models were used to examine demographic and clinical factors associated with adherence and discontinuation. Results: Patients (n = 1066) with a mean age of 66 years were included; 76.1% received first-line palbociclib+AI and 23.9% palbociclib+fulvestrant. Most patients (85.7%) initiated palbociclib at 125 mg/day. Of the 34.0% of patients with a dose reduction, 82.6% reduced from 125 to 100 mg/day. Overall, 80.0% of patients were adherent (MPR), and 38.3% discontinued palbociclib during a mean (SD) follow-up of 16.0 (11.2) and 17.4 (13.4) months, for palbociclib+fulvestrant and palbociclib+AI, respectively. Annual income below $75,000 was significantly associated with poor adherence. Older age (age 65-74 years (hazard ratio [HR] 1.57, 95% CI, 1.06, 2.33), age ≥75 years (HR 1.61, 95% CI: 1.08, 2.41)) and bone-only metastatic disease (HR 1.37, 95% CI, 1.06, 1.76) were significantly associated with palbociclib discontinuation. Conclusion: In this real-world study, >85% of patients started palbociclib at 125 mg/day and 1 in 3 had dose reductions during the follow-up. Patients were generally adherent and persistent with palbociclib. Older age, bone-only disease, and low-income levels were associated with early discontinuation or non-adherence. Further studies are needed to understand the associations of clinical and economic outcomes with palbociclib adherence and persistence.

Real-world comparative effectiveness of palbociclib plus letrozole versus letrozole in older patients with metastatic breast cancer.

BACKGROUND: Palbociclib, the first available cyclin-dependent kinase 4/6 inhibitor, plus endocrine therapy is approved for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). This study compared real-world effectiveness of palbociclib plus letrozole versus letrozole in older patients with MBC in US clinical practice. METHODS: This retrospective analysis included patients from the Flatiron Health longitudinal database. Overall, 796 women with HR+/HER2- MBC aged ≥65 years starting palbociclib plus letrozole or letrozole as first-line therapy between February 2015 and September 2018 were included. Patients were evaluated from treatment start until December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS), overall survival (OS), and real-world best tumor responses (rwBTR) were endpoints. Stabilized inverse probability treatment weighting (sIPTW) balanced patient characteristics. RESULTS: After sIPTW, 450 patients treated with palbociclib plus letrozole and 335 treated with letrozole were included; median age was 74.0 years. Median rwPFS was 22.2 (95% CI, 20.0-30.4) months for palbociclib plus letrozole versus 15.8 (12.9-18.9) months for letrozole (hazard ratio, 0.59 [0.47-0.74]; P<0.001). Median OS was not reached for palbociclib plus letrozole versus 43.4 months (30.0-not estimable) with letrozole (hazard ratio, 0.55 [0.42-0.72]; P<0.001). No interactions between age groups (65-74 and ≥75 years) and treatment groups were observed for rwPFS or OS. Rate of rwBTR was significantly higher for palbociclib plus letrozole (52.4%) versus letrozole (22.1%; odds ratio, 2.0 [1.4-2.7]; P<0.001). CONCLUSION: This analysis demonstrates the effectiveness of palbociclib combination therapy as standard-of-care for older patients with HR+/HER2- MBC in the first-line setting.

Cumulative stressful events and mental health in young adults after 10 years of Wenchuan earthquake: the role of social support.

ABSTRACTBackground: After a natural disaster, stressful events often continue to accumulate, affecting individuals in a different manner than the original disaster never occurred. However, few studies have examined these associations, the cumulative impacts of stressful events on mental health outcomes, and the role of social support. This study examined the prospective association between cumulative stressful events and mental health problems and the role of social support in young adults.Methods: 695 participants provided available data on earthquake exposure, childhood maltreatment, other negative life events, and social support at baseline. Depressive symptoms and posttraumatic stress disorder were assessed at baseline and 10 years after the earthquake (T10y). A cumulative stressful events index was used to evaluate the levels of cumulative stressful events. Linear regressions were used to explore the predictive effects.Results: Of 695 participants, 41.3%, 28.5%, and 7.9% reported one, two, and three stressful events, respectively. The associations between cumulative stressful events and mental health problems at T10y presented a dose-response pattern: those who experienced three events had the highest risk of mental health problems, followed by those who experienced two events and those who reported one event. Additionally, higher social support partially reduced the negative impact of cumulative stressful events on mental health.Conclusions: Cumulative stressful events are associated with mental health problems 10 years later in young earthquake survivors. Social support could reduce the negative impact, but its protective role disappears when stressful events accumulate at the highest level. These findings highlight the importance of assessing the cumulative impacts of stressful events and social support available to young disaster survivors and intervening to prevent worse mental health outcomes.

The associations between cumulative stressful events and mental health problems 10 years presented a dose­response pattern.Social support could buffer the negative impacts, but its protective role disappears when stressful events accumulate at the highest level.It is critical to assess the cumulative impacts of stressful events and social support available to young disaster survivors to prevent worse mental health consequences.