Clinical Behavior Research Articles

A New Construct in Undergraduate Medical Education Health Humanities Outcomes: Humanistic Practice.

Proposed educational outcomes for the health humanities in medical education range from empathy to visual thinking skills to social accountability. This lack of widely agreed-upon high-level curricular goals limits humanities educators' ability to design purposeful curricula toward clear, common ends and threatens justifications for scarce curricular time. We propose a novel approach to the hoped-for outcomes of health humanities training in medical schools, which has the potential to encompass traditional health humanities knowledge, skills, and behaviors while also being concrete and measurable: humanistic practice. Humanistic practice, adapted from the concept of ethical sensitivity, is an intentional process of applying humanities knowledge and skills to a clinical scenario by 1) noticing that the scenario requires humanities knowledge or skills, 2) informing one's clinical and interpersonal strategy and behavior with humanities knowledge or skills, 3) reflecting on the effectiveness of the strategy and behavior, and 4) reorienting to develop new approaches for future practice. The construct of humanistic practice may help address some of the foundational problems in health humanities outcomes research since it transcends the traditional diverse content domains in the health humanities, can link patient and provider experiences, and may bridge the divide among the additive, curative, and intrinsic epistemic positions of humanities to medical education.

Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype

Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype

Development of a Psychological Scale for Measuring Disruptive Clinician Behavior: Erratum.

Development of a Psychological Scale for Measuring Disruptive Clinician Behavior: Erratum.

Histopathological and Molecular Characteristics of Malignant Breast Tumors in the Kurdish Population During 2019 - 2021

Background: Breast cancer, the most prevalent cancer in women and the second leading cause of cancer-related deaths worldwide, is a complex and heterogeneous disease characterized by multiple tumor types with distinct tissue patterns, biological characteristics, and clinical behaviors. Given the critical role of histopathological and molecular characteristics in the treatment and management of breast cancer. Objectives: This study was undertaken to investigate the histopathological characteristics of malignant breast masses in the city of Sanandaj from 2019 to 2021. Methods: In this descriptive-analytical study, out of 1,631 pathology reports from breast tissue samples collected in Sanandaj, a city in northwest Iran, between 2019 and 2021, 597 (36%) malignant cases were examined for their pathological type and molecular characteristics. Data analysis was performed using SPSS 26 software, employing chi-square and Fisher's exact tests. Results: The mean age of the patients at diagnosis was 49.7 ± 11.9 years. The most prevalent molecular subtype was luminal A (56.4%), followed by triple-negative (16.7%), human epidermal growth factor receptor 2 (HER2)-positive/enriched (14.1%), and luminal B (14%). Invasive ductal carcinoma was the predominant histological type, accounting for 82.7% of cases, followed by lobular invasive carcinoma (8.2%). Papillary carcinoma accounted for 5.9% of cases, metaplastic carcinoma for 1.8%, and mucinous carcinoma for 1.3%. Higher grades at the time of diagnosis were associated with the metaplastic subtype (P < 0.001). The only biomarker that showed a significant association with pathological types of breast cancer was Ki-67. The percentage of cases positive for Ki-67 was higher in three types of breast cancer: Infiltrating ductal carcinoma, metaplastic, and papillary (intraductal) carcinoma, compared to the other types (P < 0.001). Conclusions: According to our data, infiltrating ductal and lobular carcinoma are the most prevalent pathological types, and luminal A is the most common molecular subtype among Kurdish women in Iran. It is recommended that future studies examine patient survival based on the pathological and molecular types of tumors, including the evaluation of additional biomarkers. Furthermore, comparing these results with those from other ethnic groups could provide valuable insights into the impact of ethnicity on breast cancer characteristics and outcomes.

Can on-line gait training improve clinical practice? Study protocol for feasibility randomised controlled trial of an on-line educational intervention to improve clinician’s gait-related decision-making in ambulant children and young people with cerebral palsy

BackgroundInstrumented gait analysis (IGA) is an assessment and research tool with proven impacts on clinical decision-making for the management of ambulant children and young people with cerebral palsy (CYPwCP) but is underused and variably understood by relevant clinicians. Clinicians’ difficulties in gaining expertise and confidence in using IGA are multifactorial and related to access for clinical decision-making, limited training opportunities and inability to translate this training into clinical practice.MethodsThe primary aim of this study is to test the feasibility of an educational intervention to advance clinicians’ application of gait analysis in CYPwCP, to inform a definitive trial. The secondary aim is to measure the effect that appropriate IGA training has on physiotherapists’ knowledge, skills, confidence and behaviours. This will be a two-arm feasibility randomised controlled trial with an experimental and control group. The 6-week on-line intervention uses a multicomponent approach grounded in behavioural change techniques. A repeated measures design will be adopted, whereby participants will complete outcome measures at baseline, immediately after the intervention and at 4 months. The primary outcome measures (trial feasibility-related outcomes) are recruitment and engagement. The secondary outcome measures (trial research-related outcomes) are knowledge, skills, confidence and practice change. Outcome measures will be collected via online questionnaires and during observed skill assessments. Analysis of data will use descriptive statistics, two-way mixed ANOVA model and qualitative content analysis.DiscussionThis study will determine feasibility of the definitive randomised control trial of educational intervention delivered to advance clinicians’ application of gait analysis in CYPwCP. This study offers the shift in emphasis from regarding IGA as a tool to a focus on clinicians’ requirements for access, training and a well-defined role to optimise utilisation of IGA. The impact of this should be better engagement with IGA and clinical practice change. This study will contribute to a body of educational research into clinical education of healthcare professionals and IGA training offering insight into high levels of evaluation evidence including clinical behaviour change.Trial registrationProtocol has been registered with the Open Science Framework (osf.io/nweq6) in June 2023.

Fibroblasts from HPV-negative oropharynx squamous cell carcinomas stimulate the release of osteopontin from cancer cells via the release of IL-6

IntroductionHPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood.ObjectiveTo investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV− OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk.Materials and methodsA retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication.ResultsHPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV−positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV− OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs.ConclusionThis investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.

SOLITARY CUTANEOUS NEOPLASMS: ANALYSING THE UNCERTAIN BEHAVIOUR WITH THE AID OF HISTOPATHOLOGY

INTRODUCTION: Skin tumours can be benign or malignant, resulting from proliferation of one or more skin constituents. The incidence of skin cancer has increased over last few decades, necessitating histopathological evidence to distinguish between them. OBJECTIVES: To describe epidemiology, clinical presentation, uncertain behaviour and histopathological spectrum of various skin tumours. METHODOLOGY: Present study is a prospective study conducted over a period of four years from July 2019 to July 2023 in the Out-patient Department of DVL, Government General Hospital, Anantapur. Cystic and infectious swellings and patients having multiple lesions and patients who didn’t consent for this study are excluded. All excisional biopsies of solitary cutaneous swellings are sent for Histopathological confirmation and tumours are categorised based on WHO classification. RESULTS: The study has 123 solitary cutaneous tumours, out of which, 98 cases (79.67%) were benign and 25(20.32%) are malignant. Adults aged 26-44 years are most affected (31.7%) followed by middle aged (30.08%).Males are 57(46.34%) and females are 66(53.65%).Extremities constituted the most common site with 53 cases (43.08%) followed by head and neck (29.26%). According to WHO classification of skin tumours, subcutaneous tissue tumours accounted for 42 cases (34.14%) followed by 31 cases(25.20%) of soft tissue tumours. Keratinocyte tumours are 26(21.13%), appendageal tumours are 16(13%) and least common are melanocytic and neural tumours with 4(3.25%) and 4(3.25%) respectively. Majority of benign tumours originated from subcutaneous tissues, while malignant developed from keratinocytic differentiation. CONCLUSION: In our study, most tumours had ambiguous clinical behaviour, which resulted in misdiagnosis; hence, histopathological confirmation is essential for accurate diagnosis and prompt management.

Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms.

Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results. The aim of this study is to further explore the morphologic, immunohistochemical, and genetic profile of CC-PTC, as well as to correlate these features with clinical outcomes. CC-PTC cases were identified from 3 institutions. Immunohistochemistry (ER, CDX2) and molecular testing (DNA and RNA sequencing) were performed. Clinicopathologic parameters and patient outcomes were recorded. Twelve cases (2006-2023) were identified, all in adults (age 45-91). Two presented with disease outside the thyroid gland (neck and mediastinum) and two presented with distant metastasis. Four were high-grade differentiated thyroid carcinomas (necrosis or mitoses), one of which died of disease. Four were noninvasive or minimally invasive, one of which locally recurred. Three patients had lymph node metastases. ER and CDX2 were positive in 73% and 50%, respectively. Pathogenic mutations were found in TERT promoter (n = 3), RAS (n = 2), ATM, NOTCH1, APC, and ESR1, along with cases bearing AGK::BRAF fusion (n = 1), BRAF VE1 expression (n = 1), and NF2 loss (n = 1). This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

Evaluating and Comparing the Tensile Strength and Clinical Behavior of Monofilament Polyamide and Multifilament Silk Sutures: A Systematic Review

Objective: This systematic review was carried out with the primary objective of verifying which suture (polyamide or silk) of two non-resorbable suture materials with different structures had better/greater tensile strength/resistance to tension, thereby presenting better mechanical behavior. The secondary objective was to verify which one had better performance. The null hypothesis was that both types of sutures had the same behavior. Methods: This systematic study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The focused clinical question was: “In patients that underwent oral surgery treatment (P), is there significantly higher tensile strength/resistance for silk sutures (I) or for polyamide sutures (C) when comparing the outcomes (O)?” The bibliographic search was conducted on ScienceDirect, B-On, and PubMed/MedLine between March and May 2023. The following MeSH terms were defined: sutures, breaking strength, tensile strength, oral surgery, and dentistry, which were articulated and combined using Boolean operators. There were restrictions, such as articles published in Portuguese, Spanish, or English between 1 January 2018 and 3 April 2023. The quality assessment involved the use of the Joanna Briggs Institute (JBI) checklist for RCTs and the QUIN tool (Quality Assessment Tool For In Vitro Studies) for in vitro assays. Results: Ten articles were included in this review (eight in vitro studies and two RCTs). For the RCTs, there were moderate and high levels of bias, whereas in the in vitro studies, three were classified as having a high risk of bias and five as moderate risk. The results proved that suture thread with a monofilament polyamide physical structure causes a less inflammatory reaction owing to less bacterial retention and capillarity, while multifilament sutures, such as silk, have superior mechanical characteristics. Regarding hydration, the evidence demonstrated that the preservation and stability of mechanical properties lacked uniformity. Otherwise, hyaluronic acid (HA) presents a promising solution with the same characteristics and antibacterial capabilities. Conclusion: It was possible to reject the null hypothesis that both types of sutures had the same behavior and result. It was proven by the results above that sutures with a monofilament polyamide physical structure cause a less inflammatory reaction owing to less bacterial retention and capillarity. In contrast, multifilament sutures (silk) have superior mechanical characteristics. Regarding hydration using chlorohexidine in surgical sites, the evidence demonstrated in the preservation and stability of mechanical properties lacks uniformity and congruence. However, HA seems to present a promising option with the same characteristics and antibacterial capabilities.

Myxoid Inflammatory Myofibroblastic Sarcoma: Clinicopathologic Analysis of 25 Cases of a Distinctive Sarcoma With Deceptively Bland Morphology and Aggressive Clinical Behavior.

The number of recognized sarcoma types harboring targetable molecular alterations continues to increase. Here we present 25 examples of a distinctive myofibroblastic tumor, provisionally termed "myxoid inflammatory myofibroblastic sarcoma," which might be related to inflammatory myofibroblastic tumor, and which occurred in 13 males (52%) and 12 females at a median age of 37 years (range: 7 to 79 years). Primary tumor sites were peritoneum (18 patients; 72%), paratesticular (2; 8%), chest wall (1), upper extremity (1), esophagus (1), retroperitoneum (1), and uterus (1). Nine peritoneal tumors (50%) were multifocal at presentation; all other tumors were unifocal. Tumors showed bland-to-mildly-atypical neoplastic myofibroblasts in a myxoid stroma, with prominent inflammatory infiltrates in 22 cases (88%). Most tumors showed delicate branching stromal vessels like those of myxoid liposarcoma, and most showed infiltrative growth through non-neoplastic tissue. Immunohistochemistry demonstrated expression of SMA (19/25 tumors; 76%), desmin (13/22; 59%), and CD30 (5/11; 45%), while ALK was expressed in 1 tumor (of 25; 4%) that was negative for ALK rearrangement. Sequencing of 11 tumors showed seven to harbor tyrosine kinase fusions (4 PDGFRB, 2 PML::JAK1, 1 SEC31A::PDGFRA). Two instead harbored hot spot KRAS mutations (G12V and Q61H), and 2 were negative for known driving alterations. Clinical follow-up was available for 18 patients (72%; median: 2.7 years; range: 4 mo-12.3 years). Nine patients (50%) were alive with no evidence of disease, 5 (28%) died of disease, and 4 (22%) were alive with disease. Seven patients (39%) experienced peritoneal relapse or distant metastasis. Two patients showed disease progression on conventional, nontargeted chemotherapy. The patient whose tumor harbored SEC31A::PDGFRA was treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.

Relationship between clinical belonging, professional identity, and nursing information ability among nursing interns: Model construction

BACKGROUND Clinical belonging refers to the feeling that clinical medical staff feel recognized and accepted by others or groups. The level of clinical belonging of nursing interns affects students’ learning motivation and confidence, which in turn affects their clinical practice behavior. AIM To explore the effects of professional identity and nursing information ability on clinical belonging among nursing interns and establish a relationship model for these factors. METHODS The researchers used the convenience sampling method to select 682 nursing interns from China. The survey was conducted using a general information questionnaire, clinical sense of belonging scale, nursing information ability self-assessment scale, and a nursing student professional identity questionnaire. The mediating effect of nursing information ability between their professional identity and clinical sense of belonging was analyzed using SPSS 21.0 and the path analysis in structural equation modeling. RESULTS The total scores of clinical belonging, professional identity, and nursing information ability of nursing interns were (104.29 ± 13.11) points, (57.89 ± 7.16) points, and (70.29 ± 6.20) points, respectively. Nursing information ability had a direct effect on the clinical sense of belonging (effect value = 0.46, P < 0.05). Occupational identity had a direct effect (effect value = 0.52, P < 0.05) and an indirect effect (effect value = 0.21, P < 0.05) on clinical belonging. CONCLUSION Nursing administrators in nursing colleges and hospitals should take effective measures to improve the professional identity and nursing information ability of nursing interns, as well as the clinical sense of belonging among nursing interns.

Cell lineage specific differences in clinical behavior of clinically non-functioning pituitary adenomas according to the 2017 WHO classification - a systematic review and meta-analysis

Cell lineage specific differences in clinical behavior of clinically non-functioning pituitary adenomas according to the 2017 WHO classification - a systematic review and meta-analysis

A Pediatric Interprofessional Cardiac Intensive Care Unit Intervention: CICU Teams and Loved Ones Communicating (CICU TALC) is Feasible, Acceptable, and Improves Clinician Communication Behaviors in Family Meetings.

Parents of children in the pediatric cardiac intensive care unit (CICU) are often unprepared for family meetings (FM). Clinicians often do not follow best practices for communicating with families, adding to distress. An interprofessional team intervention for FM is feasible, acceptable, and positively impacts family preparation and conduct of FM in the CICU. We implemented a family- and team-support intervention for conducting FM and conducted a pretest-posttest study with parents of patients selected for a FM and clinicians. We measured feasibility, fidelity to intervention protocol, and parent acceptability via questionnaire and semi-structured interviews. Clinician behavior in meetings was assessed through semantic content analyses of meeting transcripts tracking elicitation of parental concerns, questions asked of parents, and responses to parental empathic opportunities. Logistic and ordinal logistic regression assessed intervention impact on clinician communication behaviors in meetings comparing pre- and post-intervention data. Sixty parents (95% of approached) were enrolled, with collection of 97% FM and 98% questionnaire data. We accomplished > 85% fidelity to intervention protocol. Most parents (80%) said the preparation worksheet had the right amount of information and felt positive about families receiving this worksheet. Clinicians were more likely to elicit parental concerns (adjusted odds ratio = 3.42; 95%CI [1.13, 11.0]) in post-intervention FM. There were no significant differences in remaining measures. Implementing an interprofessional team intervention to improve family preparation and conduct of FM is locally feasible, acceptable, and changes clinician behaviors. Future research should assess broader impact of training on clinicians, patients, and families.

Defining oligometastatic state in uro-oncological cancers.

Oligometastatic tumors illustrate a distinct state between localized and systematic disease and might harbor unique biologic features. Moreover, these tumors represent a different clinical entity, with a potential of long-term disease control or even cure, therefore they receive growing attention in the field of urologic oncology. Currently, there is no consensus on the definition of oligometastatic prostate cancer, most experts limit it to a maximum of three to five lesions and involvement of no more than two organs, excluding visceral metastases. Quality data on oligometastatic bladder cancer is scarce, however, a consensus of experts defined it as a maximum of three metastatic lesions, either resectable or suitable for stereotactic therapy, without restrictions to the number of organs involved. As for kidney cancer, a maximum number of five metastases, without limitations to the location are defined as oligometastatic, with an important implication of timing of developing metastases since diagnosis of the primary tumor. Defining oligometastatic state among urological tumors reflecting their distinct biological and clinical behavior is crucial to establish a sound framework for future clinical trials, and to facilitate guideline and policy formulation for improved patient care. Advancements in molecular imaging are expected to transform the field of oligometastatic urologic tumors in the future.

Abstract PO5-03-12: Genomic differences of primary triple negative breast cancer in patients younger than 45 years vs. patients older than 45 years of age

Abstract Background: Triple negative breast cancer (TNBC) is often associated with an aggressive clinical course, especially in younger women. We previously demonstrated that there are differences in the genomic spectrum of metastatic TNBC in patients who are ≤45 years and those who are >45 years of age (Vidula et al, SABCS, 2020). Here we explore genomic differences of primary TNBC in patients ≤45 years and patients >45 years to understand variations in the overall number of non-silent mutations and proportion of patients with specific gene mutations. Methods: We obtained filtered mutation calls generated by the Multi-Center Mutation Calling in Multiple Cancers (MC3) working group (Ellrott et al, Cell Syst, 2018), from whole exome sequencing data of 9079 The Cancer Genome Atlas (TCGA) samples across 33 cancer types that had been used for the comprehensive characterization of cancer driver genes and mutations (Bailey et al, Cell, 2018). Receptor subtype and age at diagnosis of 1247 TCGA breast cancer samples were obtained from the UCSC Xena browser (Goldman et al, Nat Biotechnol, 2020). These datasets were combined to identify 119 patients with primary TNBC with harmonized high confidence mutation calls for analysis. We compared the overall number of non-silent mutations between patients ≤45 years vs. >45 years using the Wilcoxon rank sum test. We also compared the proportion of patients with non-silent mutations in genes mutated at >10% frequency between age groups using the Fisher Exact test. Results: Altogether, 25 patients ≤45 years and 94 patients >45 years were identified with primary TNBC. No significant difference in the number of non-silent mutations among patients ≤45 years vs. >45 years was seen (median [range], ≤45 years: 65 [5-228] vs. >45 years: 74 [2-742], Wilcoxon rank sum p=0.57). In total, 35 unique genes were mutated at >10% frequency in either patients ≤45 years (30 genes) or >45 years (7 genes); notably, TP53 mutations were commonly seen in both age groups (≤45 years: 76%; >45 years: 79%, p=0.79) and TTN mutations were also frequently mutated in both cohorts (≤45 years: 20%; >45 years: 27%, p=0.61). Among the 35 genes identified, 12 genes were mutated at significantly different frequencies among patients ≤45 years vs. those >45 years, as depicted in Table 1. Conclusions: Relatively high frequencies of TP53 and TTN mutations were seen in both patients ≤45 years and those >45 years with primary TNBC. However, many genes associated with varying cellular functions including motility, signaling receptors, and growth were more frequently mutated in patients ≤45 years. These results suggest that there are genomic differences of primary TNBC in patients ≤45 years vs. those >45 years. Further research is needed to validate these findings in a larger cohort of primary TNBC since genomic differences may affect tumor biology and clinical behavior. Table 1. Significant Gene Mutation Differences in Primary TNBC Based on Age. Citation Format: Neelima Vidula, Leif Ellisen, Aditya Bardia, Christina Yau. Genomic differences of primary triple negative breast cancer in patients younger than 45 years vs. patients older than 45 years of age [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-03-12.

Abstract PS02-04: Associations of sleep health with quality of life among women with newly diagnosed breast cancer: baseline results from the AMBER cohort study

Abstract Background High incidence, ageing, and advancements in early detection and clinical treatment have led to a growing breast cancer survivor population, particularly in developed countries. Sleep problems are common and persist in this population, affecting over 50% of breast cancer survivors. Good sleep health is characterized by sleep duration, sleep timing and sleep quality, and these three dimensions do not necessarily correlate with each other. This analysis aimed to investigate the associations of sleep health, characterized by sleep duration, sleep timing, and a range of metrics for sleep quality (latency, efficient, disturbance, medication, daytime dysfunction) with physical and mental well-being in women with newly diagnosed breast cancer. Methods Newly diagnosed breast cancer patients, with early-stage disease were recruited between 2012-2019 in Edmonton and Calgary, Canada, and completed the Pittsburg Sleep Quality Index (PSQI) to assess the habitual sleep duration and timing, as well as sleep latency, efficiency, disturbance, medication and daytime dysfunction. To measure quality of life, participants completed the SF-36 version-2 to assess their physical and mental well-being. Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well-being, adjusting for socio-demographic, disease, clinical and lifestyle behaviour factors. Results Among 1409 breast cancer survivors, 41% reported short or long sleep duration ( < 6 or ≥9 h/d), 41% reported habitual bedtimes after 11pm, 56% reported sleep efficiency being < 85%, 80% reported fairly good (vs. very good) sleep disturbance, 35% reported taking sleep medication in the past month, and 71% reported fairly good, fairly bad or very bad (vs. very good) daytime function. In the multivariable model, short sleep (≤6/d) was associated with worse mental well-being (-3.6, 95%CI: -4.7,-2.4) but not physical well-being (-1.5, 95%CI: -2.3,-0.7). No clinically meaningful differences in quality of life were found for sleep timing. Metrics characterizing suboptimal sleep quality were associated with poorer physical and mental well-being, with stronger associations observed for mental health well-being. Notably, only 20% and 29% women were classified as “very good” in sleep disturbance and daytime dysfunction measures, respectively. Nevertheless, even “fairly good” sleep disturbance and daytime dysfunction were associated with statistically and clinically meaningful significant poorer physical (-3, 95%CI: -3.8,-2.2) and mental (-8, 95%CI: -9,-7) well-being. Conclusion Sleep timing does not appear to affect the quality of life in a clinically meaningful manner in women newly diagnosed with breast cancer. In contrast, short sleep duration and worse sleep quality were strongly associated with poorer mental well-being in these women. Targeted interventions to improve sleep may lead to improvements in the quality of life among women with newly diagnosed breast cancer. Table 1. Association of Sleep Characteristics with SF-36 Measured Quality of Life, Physical Well-Being. Table 2. Association of Sleep Characteristics with SF-36 Measured Quality of Life, Mental Well-Being. Citation Format: Lin Yang, Qinggang Wang, Jessica McNeil, Charles Matthews, Leanne Dickau, Jeff Vallance, Margaret McNeely, S. Nicole Culos-Reed, Karen Kopciuk, Kerry Courneya, Christine Friedenreich. Associations of sleep health with quality of life among women with newly diagnosed breast cancer: baseline results from the AMBER cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS02-04.

An overview on liposarcoma subtypes: Genetic alterations and recent advances in therapeutic strategies.

Liposarcoma (LPS) is a rare malignancy of adipocytic differentiation. According to World Health Organization classification, LPS comprises of four principle subtypes Atypical lipomatous tumor/Well-differentiated liposarcoma (ATL/WDLPS), Dedifferentiated liposarcoma (WDLPS), Myxoid liposarcoma (MLPS), and Pleomorphic liposarcoma (PLPS). Each subtype can develop at any location and shows distinct clinical behavior and treatment sensitivity. ATL/ WDLPS subtype has a higher incidence rate, low recurrence, and is insensitive to radiation and chemotherapy. DDLPS is the focal progression of WDLPS, which is aggressive and highly metastasizing. MLPS is sensitive to radiation and chemotherapy, with a higher recurrence rate and metastasis. PLPS subtype is highly metastasizing, has a poor prognosis, and exhibiting higher recurrence rate. Initial histological analysis provides information for the characterization of LPS subtypes', further molecular and genetic analysis provides certain subtype specifications, such as gene amplifications and gene fusions. Such molecular genetic alterations will be useful as therapeutic targets in various cancers, including the LPS subtypes. A wide range of novel therapeutic agents based on genetic alterations that aim to target LPS subtypes specifically are under investigation. This review summarizes the LPS subtype classification, their molecular genetic characteristics, and the implications of genetic alterations in therapeutics.

Abstract PO3-05-04: Characteristics and clinical outcome of patients with HR positive HER2 low metastatic breast cancer treated with CDK 4/6 inhibitors

Abstract Introduction Breast cancer (BC) is a disease characterized by significant intra- and intertumoral heterogeneity. Hence, it is not surprising that new subtypes with distinct biological features are being discovered, even among previously well-defined BC groups. Recently, HER2-low BC emerged as a new entity with specific clinical behavior, response to treatment and prognosis. HER2-low is a subset of HER2-negative BC, with HER2 immunohistochemical (IHC) score of 1+ or 2+, without HER2 gene amplification measured by in situ hybridization (ISH). As new therapeutic options become available for HER2-low patients, the best treatment sequence is yet to be determined. Furthermore, it is important to distinguish whether there is a difference in the response to standard treatment lines, such as CDK 4/6 inhibitors in metastatic HR positive BC patients, depending on HER2-low status. Methods A retrospective study of 369 metastatic BC (mBC) cases who started CDK 4/6 inhibitor therapy from January 2018 through December 2022 at University Hospital Centre Zagreb was conducted, with prior Ethics Committee approval. All patients with HR positive HER2 negative mBC, determined by standard IHC and ISH, were included in the research. Patient demographics and clinical presentation, tumor characteristics and treatment information were collected. Progression-free survival (PFS) analysis was done with the final data cut-off date being June 1st, 2023. Type 1 right censoring was performed. The data was analyzed using the Kaplan-Meier method and Cox proportional-hazards regression for clinically relevant covariates (age, line of treatment, de novo metastatic disease, endocrine resistance, liver metastases, and detected PIK3CA mutation). Results Median follow-up was 23 months. Of the 283 patients included, 146 (51.59%) had HER2-low disease. A change in HER2 expression between primary tumor and metastasis was found in 16.96% (N=48) patients. Of them,10.25% (N=29) who were initially HER2-low, were found to be HER2-0 in metastatic disease. Meanwhile, 6.71% (N=19) of patients had a change in HER2 expression from 0 to low upon becoming metastatic. In the HER2-low group, 47.06% (N=45) patients had a PIK3CA mutation as opposed to 33.33% (N=30) in the HER2-0 group. Odds ratio for a PIK3CA mutation in HER2-low patients was 1.86 (95% confidence interval (CI): 1.01-3.43, p-value 0.046). Median PFS in the HER2-low group was 18 months (95% confidence interval (CI): 14-24) versus 23 (95% CI: 18-30) in the HER2-0 group. Using multivariable analysis an adjusted hazard ratio of 1.15 (95% CI:0.84-1.57; p-value 0.389) was calculated. Covariates associated with a statistically significant increased risk of disease progression were a higher line of therapy (HR 1.39, 95% CI 1.36-1.71, p-value 0.002) and the presence of liver metastases (HR 2.17, 95% CI 1.42-3.32, p-value 0.0004). A covariate associated with a statistically significant longer PFS was de novo metastatic disease (HR 0.63, 95% CI 0.41-0.97, p-value 0.034). Conclusion There was a trend toward worse PFS in HER2-low mBC that did not reach statistical significance. HER2-low patients were more likely to harbor PIK3CA mutations than HER2-0 patient group. Longer follow-up and a larger cohort are needed in order to make definitive conclusions. Citation Format: Katarina Čular, Kristina Kanceljak, Ana Magdalena Glas, Dora Gudelj, Marija Križić, Marina Popović, Natalija Dedić Plavetić, Maja Sirotković-Skerlev, Stjepko Pleština, Tajana Silovski. Characteristics and clinical outcome of patients with HR positive HER2 low metastatic breast cancer treated with CDK 4/6 inhibitors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-04.

Abstract PO1-24-10: B cell–mediated immunity predicts survival of patients with ER-positive breast cancer

Abstract Background: The estrogen receptor-positive (ER+) breast cancer (BC), which constitutes the majority of BC cases, exhibits highly heterogeneous clinical behavior. To aid precision treatments, we aimed to find molecular subtypes of ER+ BC representing the tumor microenvironment. Methods: We analyzed RNA-seq data of 113 BC patients and classified them according to the PAM50 intrinsic subtypes using gene expression profiles. Among them, we further focused on 48 patients with luminal-type (ER+) BC for subclassification. The Cancer Genome Atlas (TCGA) data of BC patients were utilized as a validation dataset to verify the new classification. Results: Principal component analysis clearly divided the patients into two subgroups separately from the luminal A and B classification. The top differentially expressed genes between the subgroups were distinctly characterized by immunoglobulin and B cell–related genes. We could also cluster a separate cohort of patients with luminal-type BC from TCGA into two subgroups based on the expression of a B cell–specific gene set, and patients with high B cell immune activity had better prognoses than other patients. Conclusions: Our transcriptomic approach defines a novel molecular phenotype of B cell immunity in ER+ BC that may help to predict disease prognosis. Although further researches are required, B cell immunity for ER+ BC patients may be helpful for identifying patients who are good responder to chemotherapy or immunotherapy. Work supported by grants from the National Research Foundation of Korea (NRF-2023R1A2C3003782) Citation Format: Seungbok Lee, Byung-Hee Kang, Han-Byoel Lee, Wonshik Han, In Ah Kim. B cell–mediated immunity predicts survival of patients with ER-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-24-10.

Abstract PO4-03-08: Enhanced Assessment of Clinical Behavior of TNBC and TPBC using Quantified Levels of HER2, Estrogen and Progestin Receptor Proteins and Expression of Their Cognate Genes

Abstract Background: Renewed interest in clinical relevance of low-HER2 protein in breast cancer management prompted a retrospective investigation of a unique de-identified Database of quantified biomarkers associated with patient outcomes. Currently, IHC of ER, PR and HER2 proteins provides semi-quantitative results, at times complicated by variation in methods and interpretation (cf. ASCO/CAP Guidelines). Our goal was to ascertain relationships of these clinical analytes to predict cancer relapse when quantified for protein products and cognate gene expression. Methods: Database contained 2756 quantified HER2 results by ELISA (Oncogene Sciences) or by EIA (Triton Diagnostics) of which 198 patients had associated clinical outcomes. No definition of HER2-low has been accepted for IHC, although > 50% of biopsies may be categorized as HER2-low (cf. ASCP CE Programs). Microarray results obtained for ~ 22,000 genes using RNA purified from LCM-procured carcinoma cells of 247 primary breast biopsies were analyzed. ESR1, PGR and ERBB2 gene expression levels in 276 biopsies had been validated by RTqPCR. To assess distribution and dispersion of HER2 protein, cumulative relative frequency distribution analyses were employed, focusing on cut-offs within interquartile range. Permutations and combinations of the 3 biomarkers based on IHC definitions (cf. ASCO/CAP Guidelines) were examined. Tertiles and quartiles of data sets were used to explore association between biomarker levels and clinical outcomes. Box plots depicted protein and gene expression levels, Progression-Free Survival (PFS), or Overall Survival (OS) across ER/PR/HER2 categories and compared differences using a Kruskal-Wallis ANOVA Rank Test. Cox regressions were used to contrast hazard ratios among the ER/PR/HER2 groups. Kaplan-Meier plots visualized survival rates among groups and a log-rank test detected statistical discrepancies. We investigated differences between groups for categorical variables using chi-squared tests (Fisher's exact test for non-normally distributed data), while for ordinal variables, ANOVA tests were used (Kruskal-Wallis for non-normally distributed data). Categorical variables were summarized as count (%), and ordinal variables were summarized as median [IQR]. Analyses were performed using R version 4.2.2 (Innocent and Trusting). Results: Neither quantified ER or PR alone nor ER/PR collectively were related to HER2 oncoprotein levels. Influence of menopausal status on biopsy biomarker profiles was investigated. With a median cutoff for HER2 protein, patients with ER+/PR+/HER2+ (TPBC) exhibited increased OS, whereas those with TNBC had decreased OS, of 8 combinations possible. Using tertiles and quartiles, TPBC was exhibited by 34-37% of specimens compared to TNBC, which represented 9.1-12.7% of biopsies when biomarker proteins were quantified. After qPCR data were stratified by ER/PR/HER2 status with a 50% quantile cut for HER2, 39% were TPBC and 10% were TNBC. Using microarray data with the same cutoffs, only 14% were TPBC and 17% were TNBC. Once TPBC were identified by either microarray or by qPCR, increased ESR1, PGR and ERBB2 expression collectively was associated with increased PFS and OS of patients. In general, biopsies that were TNBC or other combinations of biomarker’s gene expression correlated with poorer prognosis and overall survival. Conclusions: Quantifying levels of ER, PR and HER2 proteins as well as of ESR1, PGR and ERBB2 expression were correlated with prediction of clinical outcomes of TNBC, TPBC and patients with other biomarker subsets. Results support quantitative assessment of these biomarkers in biopsies to assess utility of the HER2-low type in personalizing breast cancer management and prediction of risk of relapse. Citation Format: James Wittliff, Michael Daniels. Enhanced Assessment of Clinical Behavior of TNBC and TPBC using Quantified Levels of HER2, Estrogen and Progestin Receptor Proteins and Expression of Their Cognate Genes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-08.