Symptoms and survivorship needs differences between "good sleepers" and "bad sleepers" in survivors of breast and gynecologic cancers.

INTRODUCTION: Although 80% of cancer survivors report symptoms of insomnia, only 28-43% meet DSM-5 criteria for this diagnosis. We sought to characterize the association between patient-reported insomnia symptoms, patient outcomes, and supportive care variables, as well as explore clinically meaningful insomnia thresholds in a sample of women diagnosed with breast and gynecologic cancers. METHODS: From July 2018-March 2019, all breast and gynecologic cancer survivors seen at the Stanford Women's Cancer Center were approached and invited to participate in the study (15% declined). Of those who consented, 273 survivors completed an online survey related to their sleep (ISI), quality of life (FACT-G), distress (PHQ-4), supportive care needs (SCNS-SF34), and symptom severity (MDASI). Survivors who scored <8 on ISI were categorized as "good sleepers," survivors with ISI ≥8 were categorized as "bad sleepers." RESULTS: 126 (46.2%) of survivors were "good sleepers," 147 (53.8%) were "bad sleepers." Good sleepers were older than bad sleepers (p < .05) but did not differ in any other demographic or any medical variables. Using hierarchical linear regression models, we found that good sleep (ISI <8) was associated with higher quality of life, lower psychological distress, increased social support, lower symptom severity, and lower supportive care needs, after accounting for demographic, medical, and treatment variables. The findings were largely replicated with an ISI cut off of 15. CONCLUSIONS: Among women treated for breast and gynecologic cancers, survivors who were good sleepers had better psychosocial outcomes, fewer supportive care needs, and lower symptom severity compared to those who reported insomnia symptoms. Results also indicate that degree of sleep impairment, whether mild or severe, has similarly poor associations with most aspects of patient functioning and symptomatic burden. Further research is needed to determine causality of these findings.

A novel approach to management of sleep-associated problems in patients with breast cancer (MOSAIC) during chemotherapy : A pilot study.

STUDY OBJECTIVES: This pilot randomized controlled trial (RCT) was conducted to assess the preliminary effects of Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) delivered by trained research staff in comparison to a sleep hygiene pamphlet control and to assess moderators of treatment effect in patients with breast cancer undergoing chemotherapy. METHODS: Of 74 participants recruited, 37 were randomized to BBT-CI and 37 were randomized to the control condition. Trained staff members delivered the intervention during chemotherapy treatments to reduce patients' burden. Insomnia was assessed with the Insomnia Severity Index (ISI), anxiety was assessed with the Spielberger State-Trait Anxiety Inventory, symptom burden was assessed with the Symptom Inventory (SI), and study staff recorded previous treatments and surgeries received by patients. RESULTS: Patients randomized to BBT-CI showed significantly greater improvements in their ISI scores compared to the sleep hygiene group. Additionally, several treatment moderators were identified. The effect of BBT-CI was greater among individuals with lower baseline state-trait anxiety, with previous surgery for cancer, and with higher baseline somatic symptom severity. CONCLUSIONS: BBT-CI shows preliminary efficacy compared to the sleep hygiene handout on insomnia in cancer patients undergoing chemotherapy. A large-phase III RCT needs to be conducted to replicate the preliminary findings.

The impact of chronotype on prosocial behavior.

INTRODUCTION: Chronotype (morningness/eveningness) is associated with preference for the timing of many types of behavior, most notably sleep. Chronotype is also associated with differences in the timing of various physiologic events as well as aspects of personality. One aspect linked to personality, prosocial behavior, has not been studied before in the context of chronotype. There are many variables contributing to who, when, and why one human might help another and some of these factors appear fixed, while some change over time or with the environment. It was our intent to examine prosocial behavior in the context of chronotype and environment. METHODS: Randomly selected adults (N = 100, ages 18-72) were approached in a public space and asked to participate in a study. If the participants consented (n = 81), they completed the reduced Morning-Eveningness Questionnaire and the Stanford Sleepiness Scale, then prosocial behavior was assessed. RESULTS/CONCLUSIONS: We found that people exhibited greater prosocial behavior when they were studied further from their preferred time of day. This did not appear to be associated with subjective sleepiness or other environmental variables, such as ambient illumination. This suggests the importance of appreciating the differentiation between the same individual's prosocial behavior at different times of day. Future studies should aim at replicating this result in larger samples and across other measures of prosocial behavior.

Circulating tumor cells as predictors of response and failure in breast cancer patients treated with preoperative chemotherapy.

AIM: To explore the significance of circulating tumor cells (CTCs) detection in the course of preoperative chemotherapy (PC) and their effect on the outcomes.
 METHODS: Fifty-five patients with stage II/III invasive breast cancer were enrolled into a preoperative clinical trial. Patients were given PC with sequential single-agent doxorubicin and paclitaxel vs paclitaxel followed by doxorubicin. Blood samples (8 mL) were collected from patients before PC, after each phase, and at 6 months intervals during follow-up. Peripheral blood mononuclear cells were isolated and enriched for epithelial cells. Quantitative RT-PCR was used to determine the presence of cytokeratin 19 (CK19) mRNA. Samples were considered positive when the PCR curve crossed the standard threshold curve.
 RESULTS: After the first phase of chemotherapy, there was a 59% overall reduction in the median tumor volume. The percentage of volume reduction did not differ between patients who presented with detectable CTCs at baseline and those who did not (p=0.89). After the second phase of chemotherapy, there was a further decrease in the median tumor volume to 93% from baseline. There was no correlation between the lack of response and the presence of CTCs either after the first (p=0.36) or second (p=0.5391) phases of PC. The presence of CTCs was a predictor of local or distant relapse (p=0.0411). The detection of CTCs did not affect overall survival (p=0.2569).
 CONCLUSION: CTCs can be used as predictors of relapse after definitive treatment of locally advanced breast cancer; however, CTCs detection in peripheral blood during the course of PC does not implicate a particular pattern of response to treatment.

Low-level expression of HER2 and CK19 in normal peripheral blood mononuclear cells: relevance for detection of circulating tumor cells.

BACKGROUND: Detection of circulating tumor cells (CTC) in the blood of cancer patients may have prognostic and predictive significance. However, background expression of 'tumor specific markers' in peripheral blood mononuclear cells (PBMC) may confound these studies. The goal of this study was to identify the origin of Cytokeratin 19 (CK19) and HER-2 signal in PBMC and suggest an approach to enhance techniques involved in detection of CTC in breast cancer patients. METHODS: PBMC from healthy donors were isolated and fractionated into monocytes, lymphocytes, natural killer cells/granulocytes and epithelial populations using immunomagnetic selection and fluorescent cell-sorting for each cell type. RNA isolated from each fraction was analyzed for CK19, HER2 and Beta 2 microglobulin (B2M) using real-time qRT-PCR. Positive selection for epithelial cells and negative selection for NK/granulocytes were used in an attempt to reduce background expression of CK19 and HER2 markers. RESULTS: In normal PBMC, CK19 was expressed in the lymphocyte population while HER-2 expression was highest in the NK/granulocyte population. Immunomagnetic selection for epithelial cells reduced background CK19 signal to a frequency of <5% in normal donors. Using negative selection, the majority (74-98%) of HER2 signal could be removed from PBMC. Positive selection methods are variably effective at reducing these background signals. CONCLUSION: We present a novel method to improve the specificity of the traditional method of detecting CTC by identifying the source of the background signals and reducing them by negative immunoselection. Further studies are warranted to improve sensitivity and specificity of methods of detecting CTC will prove to be useful tools for clinicians in determining prognosis and monitoring treatment responses of breast cancer patients.

Comparison of an industry-derived LCx Chlamydia pneumoniae PCR research kit to in-house assays performed in five laboratories.

In a multicenter comparison of PCR assays utilizing 120 quantitated samples of 16 Chlamydia pneumoniae isolates, an LCx research-use-only (RUO) PCR developed by Abbott Laboratories demonstrated 100% sensitivity on 48 samples with >1 copy of DNA per microl of specimen. The sensitivities of five in-house PCR assays ranged from 54 to 94% for the same samples. All six assays showed decreased sensitivities as the DNA copy numbers of the samples decreased. Overall, sensitivities ranged from 68% for the LCx PCR assay to 29% for one of the in-house tests. The LCx RUO PCR and three of the five in-house PCR tests reported no false positives with the 24 negative samples. Increasing the number of replicates tested increased the sensitivities of all of the assays, including the LCx PCR. The LCx RUO assay showed high reproducibility for a single technologist and between technologists, with a kappa agreement of 0.77. The within-center agreements of the five in-house PCR tests varied from 0.19 to 0.74 on two challenges of 60 specimens 1 month apart. The LCx C. pneumoniae RUO PCR shows excellent potential for use in clinical studies, which could enable standardization of results in the field.