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BackgroundCancer-related cognitive impairment (CRCI) is a common symptom in patients with breast cancer. In our previous study of 397 women with breast cancer, we identified 3 groups of patients with distinct CRCI profiles (ie, high, moderate, and low-moderate attentional function). Compared with the other 2 classes, the low-moderate class was younger, had more comorbidities, and with lower functional status.ObjectivesIn this study, we expand on this work and evaluate for differences among these latent classes in the severity of psychological (depression and anxiety) and physical (fatigue, decrements in energy, sleep disturbance, and pain) symptoms before surgery.MethodsCancer-related cognitive impairment was assessed using the Attentional Functional Index from before through 6 months after surgery. Lower Attentional Functional Index scores indicate higher levels of CRCI. Psychological and physical symptoms were assessed with valid instruments. Parametric and nonparametric tests were used to evaluate for differences in symptom severity scores among the latent classes.ResultsApproximately 60% of patients experienced CRCI (ie, moderate and low-moderate classes). Significant differences were found among the 3 classes in the severity of trait and state anxiety, depressive symptoms, fatigue, and sleep disturbance (ie, high < moderate < low-moderate). In addition, compared with the other 2 classes, the low-moderate class reported higher pain interference scores.ConclusionsThese findings suggest that women with clinically meaningful levels of persistent CRCI have a relatively high symptom burden before surgery.Implications for practiceClinicians need to routinely perform preoperative assessments of CRCI and associated symptoms and initiate therapeutic interventions.

Cancer related cognitive impairment (CRCI) is a common and persistent symptom in breast cancer patients. The Attentional Function Index (AFI) is a self-report measure that assesses CRCI. AFI includes three subscales, namely effective action, attentional lapses, and interpersonal effectiveness, that are based on working memory, inhibitory control, and cognitive flexibility. Previously, we identified three classes of patients with distinct CRCI profiles using the AFI total scores. The purpose of this study was to expand our previous work using latent class growth analysis (LCGA), to identify distinct cognitive profiles for each of the AFI subscales in the same sample (i.e., 397 women who were assessed seven times from prior to through to 6 months following breast cancer surgery). For each subscale, parametric and non-parametric statistics were used to determine differences in demographic, clinical, and pre-surgical psychological and physical symptoms among the subgroups. Three-, four-, and two-classes were identified for the effective action, attentional lapses, and interpersonal effectiveness subscales, respectively. Across all three subscales, lower functional status, higher levels of anxiety, depression, fatigue, and sleep disturbance, and worse decrements in energy were associated with worse cognitive performance. These and other modifiable characteristics may be potential targets for personalized interventions for CRCI.

We aimed to identify changes in quality of life after breast cancer treatment and compare them with the normative population data for the Slovenian population.

ContextAlthough approximately 75% of patients with breast cancer report changes in attentional function, little is known about how demographic, clinical, symptom, and psychosocial adjustment (e.g., coping) characteristics influence changes in the trajectories of attentional function over time.ObjectivesThis study evaluated interindividual variability in the trajectories of self-reported attentional function and determined which demographic, clinical, symptom, and psychosocial adjustment characteristics were associated with initial levels and with changes in attentional function from before through 12 months after breast cancer surgery.MethodsBefore surgery, 396 women were enrolled. Attentional Function Index (AFI) was completed before and nine times within the first 12 months after surgery. Hierarchical linear modeling was used to determine which characteristics were associated with initial levels and trajectories of attentional function.ResultsGiven an estimated preoperative AFI score of 6.53, for each additional month, the estimated linear rate of change in AFI score was an increase of 0.054 (P

The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment.sup.1-3. These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a unique therapeutic window for preventing metastatic disease, a comprehensive understanding of the distribution, composition and dynamics of reservoirs of dormant DTCs is imperative. Here we show that different tissue-specific microenvironments restrain or allow the progression of breast cancer in the liver--a frequent site of metastasis.sup.4 that is often associated with a poor prognosis.sup.5. Using mouse models, we show that there is a selective increase in natural killer (NK) cells in the dormant milieu. Adjuvant interleukin-15-based immunotherapy ensures an abundant pool of NK cells that sustains dormancy through interferon-[gamma] signalling, thereby preventing hepatic metastases and prolonging survival. Exit from dormancy follows a marked contraction of the NK cell compartment and the concurrent accumulation of activated hepatic stellate cells (aHSCs). Our proteomics studies on liver co-cultures implicate the aHSC-secreted chemokine CXCL12 in the induction of NK cell quiescence through its cognate receptor CXCR4. CXCL12 expression and aHSC abundance are closely correlated in patients with liver metastases. Our data identify the interplay between NK cells and aHSCs as a master switch of cancer dormancy, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing metastatic outgrowth. Liver-resident natural killer (NK) cells sustain the dormancy of disseminated breast cancer cells, and a decrease in NK cells and increase in activated hepatic stellate cells is associated with the formation of liver metastases., Author(s): Ana Luísa Correia [sup.1] [sup.2] [sup.3] , Joao C. Guimaraes [sup.4] [sup.11] , Priska Auf der Maur [sup.1] [sup.3] , Duvini De Silva [sup.1] [sup.2] [sup.11] , Marcel P. [...]

A better understanding of the features that define the interaction between cancer cells and immune cells is important for the development of new cancer therapies.sup.1. However, focus is often given to interactions that occur within the primary tumour and its microenvironment, whereas the role of immune cells during cancer dissemination in patients remains largely uncharacterized.sup.2,3. Circulating tumour cells (CTCs) are precursors of metastasis in several types of cancer.sup.4-6, and are occasionally found within the bloodstream in association with non-malignant cells such as white blood cells (WBCs).sup.7,8. The identity and function of these CTC-associated WBCs, as well as the molecular features that define the interaction between WBCs and CTCs, are unknown. Here we isolate and characterize individual CTC-associated WBCs, as well as corresponding cancer cells within each CTC-WBC cluster, from patients with breast cancer and from mouse models. We use single-cell RNA sequencing to show that in the majority of these cases, CTCs were associated with neutrophils. When comparing the transcriptome profiles of CTCs associated with neutrophils against those of CTCs alone, we detect a number of differentially expressed genes that outline cell cycle progression, leading to more efficient metastasis formation. Further, we identify cell-cell junction and cytokine-receptor pairs that define CTC-neutrophil clusters, representing key vulnerabilities of the metastatic process. Thus, the association between neutrophils and CTCs drives cell cycle progression within the bloodstream and expands the metastatic potential of CTCs, providing a rationale for targeting this interaction in treatment of breast cancer. The authors show that circulating tumour cells can be found in association with neutrophils, an interaction which supports their proliferation and their ability to seed metastasis., Author(s): Barbara Maria Szczerba [sup.1] , Francesc Castro-Giner [sup.1] [sup.2] , Marcus Vetter [sup.3] [sup.4] , Ilona Krol [sup.1] , Sofia Gkountela [sup.1] , Julia Landin [sup.4] , Manuel C. [...]

In patients with hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2−) negative breast cancer (BC), the TAILORx study showed the benefit of adding chemotherapy (CHT) to endocrine therapy (ET) in a subgroup of patients under 50 years with an intermediate Oncotype DX recurrence score (RS 11–25). The aim of the present study was to determine if the TAILORx findings, including the changes in the RS categories, impacted CHT use in the intermediate RS (11–25) group in daily practice, as well as to identify the main factors for CHT decisions. We conducted a retrospective study on 326 BC patients (59% node-negative), of which 165 had a BC diagnosis before TAILORx (Cohort A) and 161 after TAILORx publication (Cohort B). Changes in the RS categories led to shifts in patient population distribution, thereby leading to a 40% drop in the low RS (from 60% to 20%), which represented a doubling in the intermediate RS (from 30% to 60%) and an increase of 5% in the high RS (from 8–10% to 15%). The overall CHT recommendation and application did not differ significantly between cohort B when compared with A (19% vs. 22%, resp., p = 0.763). In the intermediate RS (11–25), CHT use decreased by 5%, while in the high-risk RS category (>25), there was an increase of 13%. The tumor board recommended CHT for 90% of the patients according to the new RS guidelines in cohort A and for 85% in cohort B. The decision for CHT recommendation was based on age (OR 0.93, 95% CI 0.08–0.97, p = 0.001), nodal stage (OR 4.77, 95% CI 2.03–11.22, p < 0.001), and RS categories (RS 11–25 vs. RS 0–10: OR 0.06 (95% CI 0.02–0.17), p < 0.001; RS > 26 vs. RS 11–25: OR 618.18 95% CI 91.64–4169.91, p < 0.001), but did not depend on the cohort. In conclusion, while the tumor board recommendation for CHT decreased in the intermediate RS category, there was an increase being reported in the high RS category, thus leading to overall minor changes in CHT application. As expected, among the younger women with intermediate RS and unfavorable histopathological factors, CHT use increased. [ABSTRACT FROM AUTHOR]

Background: Exposure to paclitaxel and carboplatin has the risk of developing hypersensitivity reactions (HSRs), which could necessitate using less effective treatments to avoid anaphylaxis. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen; therefore, this study investigated rates and benefits of successful desensitization in patients with gynecologic cancers (GC). Methods: We collected data from 241 patients with GC who had at least one cycle of platinum or taxane chemotherapy. The rate of HSRs and successful desensitization were evaluated, and an outcome analysis was conducted. Results: The rate of HSRs to platinum and taxane was 6.39% and 13.07%, respectively. We observed a 100% success rate of desensitization in our cohort. Patients with HSR were significantly younger (57.1 vs. 64.9 years, p=0.030) in the taxane cohort. Importantly, the overall survival (OS) of patients with platinum and taxane HSRs who underwent desensitization was comparable to that of patients with no HSRs (platinum vs. controls; median OS 60.36 vs. 60.39months, p=0.31; taxane vs. controls; OS 80.29 vs. 60.00months, p=0.59). Conclusion: Thus, we show that desensitization for platinum and taxane HSRs is safe and effective, resulting in an outcome that is well comparable to patients without HSR. Based on these observations, desensitization procedures might be considered as standard of care before switching to less effective treatment for patients with GC. [ABSTRACT FROM AUTHOR]