Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy.

BackgroundChronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. The frequency of symptomatic central nervous system (CNS) involvement is unknown but thought to be a rare phenomenon. Currently there are no known risk factors for CNS involvement.Case presentationWe describe a clinically staged low-risk CLL case that presented with symptomatic CNS involvement and progressed rapidly to death. Evaluation of the surface adhesion molecules identified a markedly altered expression pattern of the integrin, CD49d, and the tetraspanin, CD82, in the index case when compared to similar low-risk CLL cases. We found that the early Rai clinical stage CLL patients showed linear correlation for the co-expression of CD82 and CD49d. In contrast, this unique index case with CNS involvement, which has the same Rai clinical stage, had a significantly lower expression of CD82 and higher expression of CD49d.ConclusionsThese data suggest that the expression profile of CD49d and CD82 may represent potential biomarkers for patients with increased propensity of CNS involvement. Moreover, this study illustrates the critical need for a better mechanistic understanding of how specific adhesion proteins regulate the interactions between CLL cells and various tissue sites.

Acknowledging the correlation of response to therapy based on the "targeting the target" concept, FDA demonstrated confidence in precision therapy approaches by approving FoundationOne®CDx test in late 2017 as an indicated diagnostic for cancer patients. More than 100 precision therapies involving both solid and liquid malignancy have since been approved by FDA as indicated therapy in a variety of cancer types as related to correlated molecular target. We provide clinical justification of consideration for precision therapy guided by matched molecular target, specifically focusing on PI3K/mTOR/AKT, BRCA, CDK4/6, EGFR and BRAF V600E for advanced disease cancer patients who previously failed optimal NCCN guideline directed standard of care.

Background: Response to neoadjuvant chemotherapy (NAC) for breast cancer varies by tumor characteristics and therapy regimen. Studies suggest that patient ethnicity is associated with differences in disease presentation, response to treatment, and outcomes. There exists a paucity of literature on the presentation and outcomes of NAC for breast cancer in Hispanic women. Methods: This is an IRB-approved retrospective study of breast cancer patients who underwent NAC at an NCI-designated Comprehensive Cancer Center from 2005-2020. We reviewed demographics, disease presentation, response to treatment, and outcomes. ER and PR status were categorized as low positive (1-9%), positive (≥ 10%) and negative. Treatment factors reviewed included completion of chemotherapy and type of surgery performed. Treatment response was noted as percent residual cellularity (0%, <10%, 10-30%, >30-80% and >80%) in the surgical specimen and pathologic stage. Outcomes were assessed as overall survival (OS) and recurrence. Results: 365 patients received neoadjuvant chemotherapy from 2005-2020, and 196 (53.7%) self-identified as Hispanic. Median follow-up was 13.65 years. Highest clinical stage at diagnosis was most frequently IIA (31.2%), followed by IIB (32.3%), with non-significant Hispanic ethnicity differences, although Hispanic patients presented with higher clinical prognostic stages: IIIA or higher (40.5% vs. 24.0%). Hispanics more frequently had grade 3 tumors (60% vs. 48%), ER low positive (10% vs. 7%) and ER negative (48% vs. 36%) (p=0.02). No significant differences were noted in triple negative disease or HER2 positive disease. Hispanics were diagnosed at younger average ages (48.9 vs. 53.0 years, p=0.001). No statistically significant differences were noted in time from diagnosis to NAC initiation, completion of chemotherapy, or surgical treatment received (lumpectomy vs. mastectomy, and sentinel node biopsy vs. dissection). Mastectomy was more likely for late-stage disease (OR=2.73, 95% CI: 1.66-4.49, p<0.001); Hispanic women with late-stage disease had 1.09-fold higher odds of receiving mastectomy, but this was non-significant (95% CI: 0.66-1.79). No significant ethnic differences were noted in pCR (p=0.69) or residual tumor cellularity (p=0.63). There was no significant association between residual cellularity and OS. OS rates were similar for Hispanic vs. Non-Hispanic women (HR: 1.15, 95% CI: 0.64-2.08, p=0.63). No difference was noted in ethnicity-based recurrence rates (21.4 vs. 20.1%). Conclusion: Self-identified Hispanic patients were diagnosed at a younger age, presented with higher ER negative and low-positive disease and worse prognostic clinical stage. However, given standard of care chemotherapy, there were no significant differences in their treatment response or outcomes compared to non-Hispanic patients. Citation Format: Sangeetha Prabhakaran, Christopher McNicoll, Vernon S. Pankratz, Nadja Falk, Jacklyn Nemunaitis, Jain Zhou, Payton A. Sandoval-Belt. Differences in disease presentation, and treatment outcomes of neoadjuvant chemotherapy for breast cancer among Hispanics in a minority-serving institution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3686.