Impact of cyclin dependent kinase 4/6 inhibitors on breast cancer brain metastasis outcomes.

BACKGROUND: Cyclin dependent kinase 4/6 inhibitors (CDK4/6i) are recommended 1st line treatments in HR+HER2- metastatic breast cancer. However, the impact of prior CDK4/6i on the natural history of brain metastases (BM) is not well described. MATERIALS AND METHODS: We reviewed retrospective data for 363 patients with HR+HER2- BM who received a CDK4/6i (CDK-Y) between 1 Jan 2015 to 31 July 2021 and 299 patients with HR+HER2- BM who did not receive a CDK4/6i (CDK-N) between 1 Jan 2010 to 31 Dec 2014. CNS PFS and OS were assessed in patients who received CDK4/6i after BM. OS from the time of BM development was assessed between patients who received CDK4/6i before BM and the CDK-N cohort RESULTS: In the CDK-Y cohort of 363 patients, 203 (56 %) received a CDK4/6i before BM, 133 (37 %) received a CDK4/6i only after BM and 27 (7 %) received a CDK4/6i both before and after BM. Median CNS PFS was 21.4 months for patients receiving a CDK4/6i only after BM and 9.4 months for patients who received CDK4/6i both before and after BM (p = 0.006). Median OS was 24.9 months for patients receiving a CDK4/6i only after BM and 12.1 months for patients who received CDK4/6i both before and after BM (p = 0.0098). Median OS from time of BM development for patients receiving a CDK4/6i before BM versus the CDK-N cohort was 4.3 months and 7.7 months respectively (p = 0.0082). CONCLUSIONS: CDK4/6i exposure prior to BM may lead to development of resistance mechanisms which in turn reduces CNS PFS and OS upon rechallenging with a CDK4/6i after BM development. This motivates investigation of biomarkers for patient selection.

First Responders During COVID-19: Career Calling, PTSD, and Work Self-Efficacy.

INTRODUCTION: During the COVID-19 pandemic, first responders were identified as a high-risk group for developing symptoms of post-traumatic stress disorder (PTSD) and depression, which are commonly associated with negative thoughts about oneself. This may pose risk to perceptions of work self-efficacy, an integral component of employee well-being and occupational functioning. In line with the Job Demands-Resources Model (Demerouti et al., 2001), the present study examined whether the degree to which first responders' perceived career calling (i.e., a "summons" to work) served as a protective factor in the relationship between PTSD symptoms associated with the COVID-19 pandemic and perceptions of self-efficacy in the workplace. METHODS: Participants were 138 first responders from local county police and fire departments who completed online screening measures for probable PTSD and depression, as well as self-reports of work self-efficacy and career calling, between May and June 2020. Statistical analysis occurred between 2020 and 2021. RESULTS: Moderation analysis, controlling for depression and relevant covariates, revealed an interaction between PTSD symptoms and career calling, ΔR2=0.04, p=0.017. At low levels of career calling, there was a significant and negative relationship between PTSD symptoms and work self-efficacy (b=‒0.14, p=0.023), but not among first responders with average or high calling (p's>0.58). Positive screening rates were 22% for probable PTSD and 19% for depression. CONCLUSIONS: Perceiving a career calling may help protect first responders during COVID-19 from the deleterious effects of PTSD symptomatology on work self-efficacy. Prevention efforts targeting first responders with low calling strength may be warranted.

Long-term stability of respiratory sinus arrhythmia among adults with and without a history of depression.

Respiratory sinus arrhythmia (RSA) is an index of parasympathetic nervous system activity reflecting respiratory influences on heart rate. This influence is typically measured as high frequency heart rate variability (HF-HRV) or root mean square of successive differences (RMSSD) of adjacent inter-beat intervals. Examining the long-term stability of its measurement is important as levels of resting RSA have been conceptualized as a marker of individual differences; in particular, of an individual's autonomic regulation and affect-related processes, including emotion regulation. At present, it is not known if resting RSA levels reflect stable differences over a long-term period (i.e., >1 year). Even less is known about how RSA stability differs as a function of depression history and whether it relates to depression risk trajectories. In the present study, we examined the 1.5-year test-retest reliability of resting RSA using the intraclass correlation coefficient (ICC) in 82 adults: n = 41 with a history of depression (ever-depressed); n = 41 controls with no depression history (never-depressed). HF-HRV was fairly stable in both groups (ever-depressed ICC = 0.55, never-depressed ICC = 0.54). RMSSD was also fairly stable in ever-depressed adults (ICC = 0.57) and never-depressed controls (ICC = 0.40). ICC values for both indices did not differ between groups per overlapping 95% confidence intervals. Therefore, RSA stability as assessed by both frequency (HF-HRV) and time domain (RMSSD) measures was not attenuated by a depression history. Implications and the need for future research are discussed.

Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study.

BACKGROUND: Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. METHODS: We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03808662, and is complete. FINDINGS: From Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11·6 months for patients in the standard-of-care group and 12·1 months for patients in the SBRT group. The median progression-free survival was 3·2 months (95% CI 2·0-4·5) for patients in the standard-of-care group versus 7·2 months (4·5-10·0) for patients in the SBRT group (hazard ratio [HR] 0·53, 95% CI 0·35-0·81; p=0·0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10·0 months [7·2-not reached] vs 2·2 months [95% CI 2·0-4·5]; HR 0·41, 95% CI 0·22-0·75; p=0·0039), but no difference was found for patients with breast cancer (4·4 months [2·5-8·7] vs 4·2 months [1·8-5·5]; 0·78, 0·43-1·43; p=0·43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts. INTERPRETATION: The trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted. FUNDING: National Cancer Institute.

Incidence of HER2-expressing brain metastases in patients with HER2-null breast cancer: a matched case analysis.

The HER2-directed antibody-drug conjugate trastuzumab deruxtecan is active against lower levels of HER2 expression than prior-generation therapies. The rate of HER2 expression in brain metastases among patients with initially HER2-null breast cancer is undefined, and receptor discordance in advanced breast cancer with brain metastases may underestimate CNS response potential in the absence of brain metastasis sampling. In this cohort study including 136 patients with 401 samples scored according to ASCO/CAP guidelines, 15/28 patients (54%) with HER2-null primary breast cancer have detectable HER2 expression in subsequently resected brain metastases, a significant discordant population.

New strategies for the treatment of breast cancer with leptomeningeal metastasis.

PURPOSE OF REVIEW: Leptomeningeal metastasis is a complication of metastatic breast cancer that has a rising incidence likely due to the increased availability of novel systemic therapies, which have improved survival with better extracranial disease control but with limited intracranial efficacy. A poor prognosis of less than 6 months has historically been associated with leptomeningeal metastasis and it is often an exclusion factor for enrollment in clinical trials. There are limited evidence-based data supporting use of therapeutics in leptomeningeal metastasis patients and recommendations are largely derived from retrospective reports and small prospective studies. However, in recent years, there has been a surge in effective modern therapeutics with promising intracranial activity. RECENT FINDINGS: The study aims to review the most recent updates in the management of leptomeningeal metastasis in breast cancer. We discuss the effectiveness and limitations of intrathecal administration, predictive biomarkers in the cerebrospinal fluid, proton radiation therapy and promising new systemic therapies such as antibody drug conjugates. SUMMARY: Ongoing development of clinical trials that allow inclusion of leptomeningeal metastasis are essential for establishing efficacy potential and discovering new treatment options in this population of great unmet need.

Symptomatic Necrosis With Antibody-Drug Conjugates and Concurrent Stereotactic Radiotherapy for Brain Metastases.

This cohort study investigates whether brain metastases that manifest after stereotactic radiotherapy with concurrent antibody-drug conjugates are associated with an increased risk of symptomatic radiation necrosis.

Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases.

BACKGROUND: Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM. METHODS: We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint. RESULTS: 7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine. CONCLUSIONS: The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.

Effects of current and past depressive episodes on behavioral performance and subjective experience during an N-back task.

BACKGROUND AND OBJECTIVES: Depression impairs working memory (WM). And, while many studies have documented impairment in WM during depression remission, those using the N-back task did not find differences between individuals with remitted depression and healthy controls. One reason for these findings may be that certain depression phenotypes, such as the childhood-onset form, which is likely to be associated with persistent WM problems, are underrepresented or unevenly represented in the studies. Because childhood-onset depression (COD) affects individuals while cognitive development is still ongoing, it is more likely to have lasting detrimental effects, as evidenced in residual memory impairment, than depression that onsets later in life. Further, it is unclear if depression episodes have cumulative effects on WM when measured via the N-back. METHODS: We examined the effects of depression on WM performance (response time, accuracy, signal detection d') and subjective experience (difficulty, mental effort required) during a four-level N-back task among 112 adults with COD (42 currently depressed; 70 remitted depressed) and 80 never-depressed controls. RESULTS: Compared to never-depressed controls, there was minimal evidence of impaired WM performance among participants with remitted or current depression; the groups also reported overall similar subjective experiences during the N-back. Notably, number of lifetime depressive episodes had a detrimental cumulative effect on response accuracy and d'. LIMITATIONS: WM was assessed only in regard to verbal memory. The sample size of currently depressed cases was smaller than that of the other groups. CONCLUSIONS: WM remains largely intact among adults with remitted COD, but increased number of depression episodes worsens WM performance.

History of major depressive disorder is associated with differences in implicit learning of emotional faces.

Major depressive disorder is often associated with worsened reward learning, with blunted reward response persisting after remission. In this study, we developed a probabilistic learning task with social rewards as a learning signal. We examined the impacts of depression on social rewards (facial affect displays) as an implicit learning signal. Fifty-seven participants without a history of depression and sixty-two participants with a history of depression (current or remitted) completed a structured clinical interview and an implicit learning task with social reward. Participants underwent an open-ended interview to evaluate whether they knew the rule consciously. Linear mixed effects models revealed that participants without a history of depression learned faster and showed a stronger preference towards the positive than the negative stimulus when compared to the participants with a history of depression. In contrast, those with a history depression learned slower on average and displayed greater variability in stimulus preference. We did not detect any differences in learning between those with current and remitted depression. The results indicate that on a probabilistic social reward task, people with a history of depression exhibit slower reward learning and greater variability in their learning behavior. Improving our understanding of alterations in social reward learning and their associations with depression and anhedonia may help to develop translatable psychotherapeutic approaches for modification of maladaptive emotion regulation.

Examining between- and within-person effects of the self-stigma of seeking psychological help on the therapeutic working alliance: The moderating role of psychological distress.

The self-stigma (i.e., shame) associated with psychotherapy is a prominent barrier to seeking psychological help, but less is known about its effects after treatment begins. Evidence suggests that self-stigma may interfere with the formation of the therapeutic alliance, but no studies have examined this throughout the course of psychotherapy. Self-stigma's erosion of the alliance may be most pronounced when clients experience heightened psychological distress, but this also has not been examined. Therefore, the present study addresses these omissions among 37 clients who completed at least three therapy sessions for research credit. Participants completed measures of self-stigma and past-week symptoms of distress before each session and ratings of the working alliance after. Predictor variables were disaggregated into between-person (time-invariant or average levels) and within-person (time-variant or session-by-session changes) components to enable investigation of for whom (and under what conditions) self-stigma was associated with the therapeutic alliance. Results indicated that higher levels of self-stigma (between and within persons) predicted a worse alliance. When examined as an interaction effect alongside distress in a multilevel moderation model, higher between-person ratings of self-stigma predicted a weaker therapist-client alliance across levels (M ± 1 SD) of within-person distress. Notably, its effects became more pronounced as symptoms of distress increased, indicating a period in which clients are simultaneously most likely to need help yet least likely to feel allied with their therapist. Findings highlight the importance for therapists to simultaneously monitor and consider both average and session-by-session fluctuations in self-stigma and distress to develop and maintain the working alliance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Economic Choice and Heart Rate Fractal Scaling Indicate That Cognitive Effort Is Reduced by Depression and Boosted by Sad Mood.

BACKGROUND: People with depression typically exhibit diminished cognitive control. Control is subjectively costly, prompting speculation that control deficits reflect reduced cognitive effort. Evidence that people with depression exert less cognitive effort is mixed, however, and motivation may depend on state affect. METHODS: We used a cognitive effort discounting task to measure propensity to expend cognitive effort and fractal structure in the temporal dynamics of interbeat intervals to assess on-task effort exertion for 49 healthy control subjects, 36 people with current depression, and 67 people with remitted depression. RESULTS: People with depression discounted more steeply, indicating that they were less willing to exert cognitive effort than people with remitted depression and never-depressed control subjects. Also, steeper discounting predicted worse functioning in daily life. Surprisingly, a sad mood induction selectively boosted motivation among participants with depression, erasing differences between them and control subjects. During task performance, depressed participants with the lowest cognitive motivation showed blunted autonomic reactivity as a function of load. CONCLUSIONS: Discounting patterns supported the hypothesis that people with current depression would be less willing to exert cognitive effort, and steeper discounting predicted lower global functioning in daily life. Heart rate fractal scaling proved to be a highly sensitive index of cognitive load, and data implied that people with lower motivation for cognitive effort had a diminished physiological capacity to respond to rising cognitive demands. State affect appeared to influence motivation among people with current depression given that they were more willing to exert cognitive effort following a sad mood induction.

Breast Cancer Brain Metastases: Achilles' Heel in Breast Cancer Patients' Care.

Brain metastases (BM) significantly affect the prognosis as well as the quality of life of breast cancer (BC) patients. Although advancements in neurosurgical and radiotherapy techniques improve local control and symptom management, BM remains associated with a poor prognosis. In addition, the efficacy of currently approved systemic therapies in central nervous system (CNS) compartment is still limited, especially after progression on local therapy. The blood-brain barrier (BBB) has been recognized as a mechanism of primary resistance to many chemotherapeutic agents and targeted therapies due to low drug penetration. Other mechanisms of primary and secondary resistance are still unclear and may vary across the BC subtypes. New small molecules have demonstrated efficacy in BM, in particular for the HER2-positive subtype, with a benefit in survival. A new era has begun in the field of BM, and many trials specifically designed for this population are currently ongoing. The BC research community needs to address this call with the final aim of improving the efficacy of systemic therapy in CNS compartment and ultimately preventing the occurrence of BM.

Associations of suffering with facets of health and well-being among working adults: longitudinal evidence from two samples.

Suffering is an experiential state that every person encounters at one time or another, yet little is known about suffering and its consequences for the health and well-being of nonclinical adult populations. In a pair of longitudinal studies, we used two waves of data from garment factory workers (Study 1 [T1: 2017, T2: 2019]: n = 344) and flight attendants (Study 2 [T1: 2017/2018, T2: 2020]: n = 1402) to examine the prospective associations of suffering with 16 outcomes across different domains of health and well-being: physical health, health behavior, mental health, psychological well-being, character strengths, and social well-being. The primary analysis involved a series of regression analyses in which each T2 outcome was regressed on overall suffering assessed at T1, adjusting for relevant sociodemographic characteristics and the baseline value (or close proxy) of the outcome assessed at T1. In Study 1, associations of overall suffering with worse subsequent health and well-being were limited to a single outcome on each of the domains of physical health and mental health. Overall suffering was more consistently related to worse subsequent health and well-being in Study 2, with associations emerging for all but two outcomes. The pattern of findings for each study was largely similar when aspects of suffering were modeled individually, although associations for some aspects of suffering differed from those that emerged for overall suffering. Our findings suggest that suffering may have important implications for the health and well-being of worker populations.

Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis.

PURPOSE: Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT. PATIENTS AND METHODS: We conducted a randomized, phase II trial of pCSI versus IFRT in patients with non-small-cell lung cancer and breast cancers with LM. We enrolled patients with other solid tumors to an exploratory pCSI group. For the randomized groups, patients were assigned (2:1), stratified by histology and systemic disease status, to pCSI or IFRT. The primary end point was CNS PFS. Secondary end points included overall survival (OS) and treatment-related adverse events (TAEs). RESULTS: Between April 16, 2020, and October 11, 2021, 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively. At planned interim analysis, a significant benefit in CNS PFS was observed with pCSI (median 7.5 months; 95% CI, 6.6 months to not reached) compared with IFRT (2.3 months; 95% CI, 1.2 to 5.8 months; P < .001). We also observed OS benefit with pCSI (9.9 months; 95% CI, 7.5 months to not reached) versus IFRT (6.0 months; 95% CI, 3.9 months to not reached; P = .029). There was no difference in the rate of grade 3 and 4 TAEs (P = .19). In the exploratory pCSI group, 35 patients enrolled, the median CNS PFS was 5.8 months (95% CI, 4.4 to 9.1 months) and OS was 6.6 months (95% CI, 5.4 to 11 months). CONCLUSION: Compared with photon IFRT, we found pCSI improved CNS PFS and OS for patients with non-small-cell lung cancer and breast cancer with LM with no increase in serious TAEs.

Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial.

Importance: Patients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM. Objective: To compare clinical outcomes in patients with BM treated with etirinotecan pegol vs chemotherapy of the physician's choice in a confirmatory trial. Design, Setting, and Participants: This study was a phase 3, open-label, randomized clinical trial (ATTAIN) in patients with metastatic breast cancer and a history of stable pretreated BM who experienced disease progression while receiving chemotherapy in the metastatic setting. The trial took place at 47 sites in 10 countries, and patients were enrolled between March 7, 2017, and November 6, 2019. Interventions: Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). Main Outcomes and Measures: The primary end point was OS. Key secondary end points included progression-free survival, objective response rate, duration of response, and the clinical benefit rate. Results: A total of 178 female patients (9 [5.1%] Asian, 8 [4.5%] Black or African American, and 123 [69.1] White individuals) were randomized to receive treatment with etirinotecan pegol (92 [51.7%]; median [range] age, 53 [27-79] years) or chemotherapy (86 [48.3%]; median [range] age, 52 [24-77] years). Median OS was similar in both groups (etirinotecan pegol, 7.8 months; chemotherapy, 7.5 months; hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P = .60). Median progression-free survival for non-central nervous system metastases per blinded independent central review for etirinotecan pegol vs chemotherapy was 2.8 and 1.9 months (HR, 0.72; 95% CI, 0.45-1.16; P = .18) and 3.9 vs 3.3 months, respectively, for central nervous system metastases (HR, 0.59; 95% CI, 0.33-1.05; P = .07). Safety profiles between the groups were largely comparable. Conclusions and Relevance: The results of the ATTAIN randomized clinical trial found no statistically significant difference in outcomes between treatment with etirinotecan pegol and chemotherapy in patients with BM. However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research. Trial Registration: ClinicalTrials.gov Identifier: NCT02915744.

Ecological momentary assessment of affect in depression-prone and control samples: Survey compliance and affective yield.

BACKGROUND: Ecological momentary assessment (EMA) is a high-frequency ambulatory data collection approach that has come to be widely used in emotion research. It therefore is timely to examine two features of EMA needed for a successful study: compliance with survey prompts and high affective yield (survey prompts that capture affect experience). We posit that compliance may be subject to temporal variation (time-of-day, days in study) and individual differences (depression history), and that affective yield may also differ by social context. METHODS: We examined these issues in a sample of 318 young adults (Mage = 24.7 years, SD = 2.7), including those with current depression (n = 28), remitted depression (n = 168) and never-depressed controls (n = 122) who participated in a 7-day EMA protocol of negative and positive affect (NA and PA, respectively). RESULTS: The overall compliance rate was 91% and remained stable across the survey week. However, subjects were significantly less likely to respond to the first daily prompt compared to those that followed. The likelihood of capturing NA and PA decreased with each EMA protocol day, and affective yield across social contexts differed by participants' depression status. LIMITATIONS: The sample was largely comprised of White young adults. Relative to the remitted and control groups, the sample size for the currently depressed was unbalanced. CONCLUSION: Researchers can optimize compliance and affective yield within EMA by considering depression, time-of-day, study duration, and social context. Clinicians using EMA to monitor affect may benefit from considering these parameters.

The effects of group counseling and self-affirmation on stigma and group relationship development: A replication and extension.

The stigma of seeking counseling and negative attitudes about counseling are primary barriers to its use. In the only known study examining the utility of attending a group counseling session to ameliorate stigma (no control group), participation was associated with reductions in self-stigma (Wade et al., 2011). Self-affirmation interventions have shown promising results in reducing stigma and promoting positive expectations about counseling, but no research has examined its effects on a counseling session. In the present, two-part study, 172 college students who had previously completed an online screening survey, including measures of stigma, participated in a single session of group counseling at a mental health clinic. Upon arrival, participants completed a self-affirmation intervention before viewing psychoeducation (n = 66; 12 groups) or only viewed psychoeducation (n = 72; 14 groups); both groups then completed a session of group counseling. After, participants completed these same measures along with measures of group relationships. The remaining participants (n = 34; 7 groups) viewed psychoeducation and completed the same stigma measures before being informed of randomization to the wait-list control condition. Our results replicate and extend findings from Wade et al. (2011): Completing a single session of group counseling reduced self-stigma and promoted positive attitudes toward counseling. Further, completing self-affirmation reduced postsession perceptions of public stigma. Self-affirmation had no impact on group relationships. Overall, findings suggest the utility of offering a "try-out" session of group counseling as a stigma-reduction intervention; preceding with a brief self-affirmation intervention provides further benefits by reducing perceptions of public stigma. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Incidence of brain metastases in patients with early HER2-positive breast cancer receiving neoadjuvant chemotherapy with trastuzumab and pertuzumab.

The addition of pertuzumab (P) to trastuzumab (H) and neoadjuvant chemotherapy (NAC) has decreased the risk of distant recurrence in early stage HER2-positive breast cancer. The incidence of brain metastases (BM) in patients who achieved pathological complete response (pCR) versus those who do not is unknown. In this study, we sought the incidence of BM in patients receiving HP-containing NAC as well as survival outcome. We reviewed the medical records of 526 early stage HER2-positive patients treated with an HP-based regimen at Memorial Sloan Kettering Cancer Center (MSKCC), between September 1, 2013 to November 1, 2019. The primary endpoint was to estimate the cumulative incidence of BM in pCR versus non-pCR patients; secondary endpoints included disease free-survival (DFS) and overall survival (OS). After a median follow-up of 3.2 years, 7 out of 286 patients with pCR had a BM while 5 out of 240 non-pCR patients had a BM. The 3-year DFS was significantly higher in the pCR group compared to non-pCR group (95% vs 91 %, p = 0.03) and the same trend was observed for overall survival. In our cohort, despite the better survival outcomes of patients who achieved pCR, we did not observe appreciable differences in the incidence of BM by pCR/non-pCR status. This finding suggests that the BM incidence could not be associated with pCR. Future trials with new small molecules able to cross the blood brain barrier should use more specific biomarkers rather than pCR for patients' selection.