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Melanoma brain metastasis (MBM) is linked to poor prognosis and low overall survival. We hypothesized that melanoma circulating tumor cells (CTC) possess a gene signature significantly expressed and associated with MBM. Employing a multipronged approach, we provide first-time evidence identifying a common CTC gene signature for ribosomal protein large/small subunits (RPL/RPS) which associate with MBM onset and progression. Experimental strategies involved capturing, transcriptional profiling, and interrogating CTCs, either directly isolated from blood of patients with melanoma at distinct stages of MBM progression or from CTC-driven MBM in experimental animals. Second, we developed the first MRI CTC-derived MBM xenograft model (MRI-MBM CDX) to discriminate MBM spatial and temporal growth, recreating MBM clinical presentation and progression. Third, we performed the comprehensive transcriptional profiling of MRI-MBM CDXs, along with longitudinal monitoring of CTCs from CDXs possessing and/or not possessing MBM. Our findings suggest that enhanced ribosomal protein content/ribogenesis may contribute to MBM onset. Because ribosome modifications drive tumor progression and metastatic development by remodeling CTC translational events, overexpression of the CTC RPL/RPS gene signature could be implicated in MBM development. Collectively, this study provides important insights for relevance of the CTC RPL/RPS gene signature in MBM, and identify potential targets for therapeutic intervention to improve patient care for patients with melanoma diagnosed with or at high risk of developing MBM. Significance: This study reports first evidence of RPL/RPS gene signature driving melanoma brain metastasis. Complex multilevel approach was performed to identify MBM signature and confirm its relevance to clinical settings. Novel MRI CTC-derived MBM mouse xenograft was established to monitor MBM spatial and temporal development and progression.

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Melanoma brain metastasis (MBM) is linked to poor prognosis and low overall survival. We hypothesized that melanoma circulating tumor cells (CTC) possess a gene signature significantly expressed and associated with MBM. Employing a multipronged approach, we provide first-time evidence identifying a common CTC gene signature for ribosomal protein large/small subunits (RPL/RPS) which associate with MBM onset and progression. Experimental strategies involved capturing, transcriptional profiling, and interrogating CTCs, either directly isolated from blood of patients with melanoma at distinct stages of MBM progression or from CTC-driven MBM in experimental animals. Second, we developed the first MRI CTC-derived MBM xenograft model (MRI-MBM CDX) to discriminate MBM spatial and temporal growth, recreating MBM clinical presentation and progression. Third, we performed the comprehensive transcriptional profiling of MRI-MBM CDXs, along with longitudinal monitoring of CTCs from CDXs possessing and/or not possessing MBM. Our findings suggest that enhanced ribosomal protein content/ribogenesis may contribute to MBM onset. Because ribosome modifications drive tumor progression and metastatic development by remodeling CTC translational events, overexpression of the CTC RPL/RPS gene signature could be implicated in MBM development. Collectively, this study provides important insights for relevance of the CTC RPL/RPS gene signature in MBM, and identify potential targets for therapeutic intervention to improve patient care for patients with melanoma diagnosed with or at high risk of developing MBM.Significance:This study reports first evidence of RPL/RPS gene signature driving melanoma brain metastasis. Complex multilevel approach was performed to identify MBM signature and confirm its relevance to clinical settings. Novel MRI CTC-derived MBM mouse xenograft was established to monitor MBM spatial and temporal development and progression.

Introduction: Breast Cancer Awareness Month (BCAM) has been used for decades to increase awareness and screening for breast cancer but it’s reach and effectiveness is difficult to judge. Using Internet Search Interest (ISI) could allow better evaluation of BCAM effects.Methods: Using Google Trends, we evaluated the ISI of a given term(s) as compared to that cancer’s awareness month. The ISI represents population level Google internet searches relative to the highest number of searches for the United States from 2004-2019 with a max number of 100. The ISI for breast cancer and mammogram in October, which is BCAM, was compared against all other months during this period. Results: The BCAM of October was associated with statistically significant more ISI for breast cancer 77.0 vs. 34.6 (95% CI 69.5-84.5, CI 32.9-35.3, p < 0.0005) as compared to the rest of the year. ISI for mammogram was similar (41.6 vs. 60.2, 95% CI 39.4-43.7, 48.5-71.9, p = 0.007). There was significant differences between the top half of states with Mississippi (100), Delaware (97) and West Virginia (95) having the highest ISI while Nevada (60), Oregon (60) and Utah (57) the lowest (87.6 vs 71.8, 95% CI, 85.5-89.7, 69.0-74.6, p < 0.0005). There was significant differences between the top half of 208 United States metro areas with Rochester MN (100), Greenwood MS (85) and Jackson MS (80) having the highest ISI while Salt Lake City UT (43), Idaho Falls UT (41) and Roanoke VA (40) the lowest (67.5 vs 54.4, 95% CI, 66.4-68.6, 53.4-55.4, p < 0.0005). Conclusion: ISI suggests that BCAM is effective at increasing breast cancer awareness with significant heterogeneity across states and metro areas. This publicly available free tool can be used to assess penetrance of awareness campaigns in a time sensitive manor for future targeting of populations with low breast cancer awareness. Future research is needed to correlate outcomes and ISI. Citation Format: Diamone A. Gathers, Vernon S. Pankratz, Bernard Tawfik. Using big data to gauge effectiveness of breast cancer awareness month [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-24.

Background: A Breast Cancer Nurse Navigator (BCNN) is a designated nurse specially trained to follow and support patients and their loved ones through their cancer treatment. BCNNs have been shown to improve patient experience, improve quality of life, and reduce delays in care. In 2017, the University of New Mexico Comprehensive Cancer Center (UNMCCC) instituted a Nurse Navigator program aimed at improving the treatment experience of the unique patient population the institution is intended to serve, primarily minority, rural, and economically disadvantaged patients. Approximately 22% of New Mexicans live in rural areas, and New Mexico ranks 49thin the nation in terms of poverty, with 19.7% of the population living below the poverty line. Both of these predispose to across the board poorer health outcomes and poorer cancer outcomes, including a link between poverty and higher cancer mortality. New Mexico is home to over 200,000 Native Americans, making up 10.4% of the state population, and 1 million Hispanics, making up 48% of the state population. Both groups suffer worse outcomes, increased barriers to care, and overall measurably lower quality of life. UNMCCC’s BCNN program aligns with the American Society of Clinical Oncology’s new task force to address the rural cancer care gap. Methods: Surveys to assess patient satisfaction and services utilized were administered anonymously during regularly scheduled appointments at UNMCCC between April 29 and June 7, 2019 to breast cancer patients, both those under the care of the BCNN and those whose care began prior to the beginning of the program. There were 32 “non-navigated” patients responding, and 54 “navigated” patients. Yes/no questions were converted to binary and Likert Scale questions were converted to scores ranging from 1-5, 1 signifying “Strongly Agree” with 5 signifying “Strongly Disagree.” Results were assessed using two sample T-Tests assuming unequal variances. Results: Navigated patients more strongly agreed that they were prepared for the beginning of treatment when compared to their non-navigated peers (1.558 vs 2.103, p=.020), and showed a decreased desire for an after treatment summary (.918 vs 1.0, p=.044). They also reported that calls were returned promptly when compared to their non-navigated peers (1.33 vs 1.8, p=.003). Navigated patients were subjectively more likely to agree that office staff were knowledgeable about their treatment plan than the non-navigated patients (1.509 vs 1.806, p=.134). Navigated patients were more likely to agree that the BCNN helped them understand treatment plans (1.549 vs 1.710, p=.437), took their concerns seriously (1.434 vs 1.516, p=.579), and helped manage side effects (1.689 vs 1.923, p=.356). Conclusions: The navigated patients perceived that their calls were returned more quickly, which improves patient satisfaction and confidence in the treatment plan and care team. Navigated patients also displayed stronger agreement that they were prepared for the beginning of their treatment, which was supported with a decreased desire for an after treatment summary, suggesting that patients felt overall more knowledgeable about their care. There were subjective improvements in all other treatment related metrics that were not statistically significant though likely limited by the small sample size. This study shows that patients in a unique minority, rural, and economically disadvantaged population subjectively report better understanding of and engagement with the health care system when assisted by a BCNN during the treatment of curative breast cancer, an effect which has not been well demonstrated before. Acknowledgements: Special thanks to Patricia Kuhne and Susan Martinez for their assistance, without which this project would not have been possible. Citation Format: Michael Williams, Dianne Nielson, Zoneddy Dayao, Ursa Brown-Glabberman, Bernard Tawfik. Patient reported measures of a breast cancer nurse navigator program in a minority, rural, and economically disadvantaged patient population [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-10.

Background Population-based studies to examine cervical cancer screening and prevention among sexual and gender diverse (SGD) individuals have been limited. We conducted a state-wide survey in New Mexico (NM) to examine differences in cervical cancer screening and HPV vaccination uptake based on gender and sexual orientation. Methods The survey was advertised using mailed flyers, social media, and targeted internet ads across the state. We received a total of 2534 responses, of which 797 respondents were cervical cancer screening eligible (i.e., between 21-65 years old, had a cervix, and did not have a prior cervical cancer diagnosis) and provided information about cervical cancer screening and were included in this analysis. Descriptive statistics were conducted using SAS 9.4. Results Of the 797 respondents, 83% were 21 - 40 years old, 44% were white, 34% reported an annual household income below $50,000, 83% were employed, 81% had health insurance, and 73% reported having a primary care provider. Fourteen percent were transgender men or nonbinary, 86% were cisgender women, 34% were bisexual, 48% were lesbian, and 18% were queer. While there were no statistical differences in self-reported cervical cancer screening based on gender identity, 31% of cisgender women and 25% of transgender men and nonbinary individuals reported never receiving a Pap test. The top reason for never receiving a Pap test among cisgender women was that their healthcare provider told them they did not need it (17%) and for transgender men and nonbinary individuals the top reasons were that they had an HPV vaccine (21%) or that it was too painful, unpleasant, or embarrassing (21%). There were significant statistical differences based on sexual orientation for receiving a Pap test (p Citation Format: Prajakta Adsul, Deborah Kanda, Emily Wu, Molly McClain, Vernon Shane Pankratz, Shiraz Mishra, Bernard Tawfik, Uma Nair, Tamara Stimatze, Purnima Madhivanan, Miria Kano. Examining differences based on gender and sexual orientation for cervical cancer screening and prevention behaviors [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A097.