Cyberchondria is defined as an increase in anxiety about one's health status as a result of excessive online searches. McElroy and Shevlin (2014) developed the first multidimensional, self-report measure of this construct-the Cyberchondria Severity Scale (CSS). The CSS consists of 33 items which can be summed to form a total score, and/or 5 subscale scores. The aim of the present study was to develop a short-formversion of the CSS, removing the 'Mistrust' subscale. Participants were undergraduate students from two UK universities (N=661, 73% female, Mage = 22.19 years, SD =5.88). Students completed the CSS, Short Health Anxiety Inventory (SHAI) and Generalised Anxiety Disorder Assessment (GAD-7). Twelve items were chosen for retention in the short-form based on an exploratory factor analysis. These itemscorresponded to the 4 factors previously identified in the 33-item scale (minus the 'Mistrust' subscale). Confirmatory factor analysis was used to validate the structure of the CSS-12. Confirmatory bifactor modelling indicated that the majority of item covariance was accounted for by a general cyberchondria factor. Construct validity was assessed by examining associations with the SHAI and GAD-7, with stronger correlations observed between the CSS-12 and the SHAI (compared to the GAD-7). The CSS-12 is a brief, reliable, and valid measure of worry/anxiety attributable to excessive online health research.

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Background Treatment with combination chemo-immunotherapy has become the front-line standard for eligible patients with PD-L1 positive mTNBC. PD-L1 is the only approved biomarker for pembrolizumab in metastatic breast cancer for response to combination chemo-immunotherapy, however given that it is not predictive of response in all cases additional biomarkers are needed. Tumor infiltrating lymphocytes (TILs) have been shown to be both predictive and prognostic in operable TNBC, but there are fewer data regarding the role of TILs in mTNBC. In this study we report the associations between TILs and outcomes in patients treated prospectively on the ENHANCE-1 study with eribulin and pembrolizumab. Methods ENHANCE-1 was a single arm phase Ib/II trial which evaluated the efficacy and safety of eribulin and pembrolizumab in 167 patients (pts) with mTNBC who had received 0-2 prior lines of therapy (66 pts in the first line setting [stratum 1] and 101 pts with 1-2 prior lines of therapy [stratum 2]). Objective response rate (ORR) was defined as percentage of pts with either complete response (CR) or partial response (PR) by RECIST 1.1. The ORR was 25.8% in stratum 1 and 21.8% in stratum 2. Stromal TILs (sTIL) and intratumoral TILs were evaluated on whole slide H&E sections from biopsy specimens used for enrollment on ENHANCE-1 by breast pathology according to the International TILs Working Group guidelines. PD-L1 positivity was determined via immunohistochemistry using the Agilent 22C3 antibody. We also assessed TIL density digitally using machine learning classifiers to identify tumor/stromal tissue areas and individual lymphocytes. Results We found that there was statistically significant increase in sTIL counts in responders compared to non-responders in stratum 1 (p=0.002) but not in stratum 2 (p=0.99). We did not find any associations between intratumoral TILs and response. Quantitative PD-L1 scoring via combined proportion score (CPS) was also positively associated with response in stratum 1 (p=0.01) but not in stratum 2 (p=0.34). We also find that sTIL counts are most correlated to CPS scores (continuous) for non-responders within stratum 1 (R2=+0.55, p< 0.01). Conclusion In this population of patients with mTNBC treated prospectively with eribulin and pembrolizumab, sTILs and PDL1 CPS were each individually associated with a positive response in patients treated with front-line combination chemo-immunotherapy. Neither was predictive for patient response in stratum 2. One important caveat is the biopsies were not required immediately prior to enrollment, possibly confounding the tumor microenvironment (TME) at the time of analysis. Our data contribute to emerging data that sTILs can act as a biomarker for response to immune checkpoint inhibition when utilized in the front-line setting for mTNBC. Further characterization of the TME via quantitative immunofluorescence is ongoing. This study was funded by Eisai IIS-E7389 Citation Format: Mathew Kearney, Hua Guo, Rami Vanguri, Qi Wang, Michelle Garlin, Courtney Connelly, Kevin Kalinsky, Eileen P. Connolly. Role of tumor infiltrating lymphocytes and PD-L1 expression in the response to eribulin and pembrolizumab in metastatic triple negative breast cancer (mTNBC) on the ENHANCE1 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-23.