Browsing by Author "Marks, Jeffrey R."

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    Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts
    (Elsevier, 2022-12-12) Strand, Siri H.; Rivero-Gutiérrez, Belén; Houlahan, Kathleen E.; Seoane, Jose A.; King, Lorraine M.; Risom, Tyler; Simpson, Lunden A.; Vennam, Sujay; Khan, Aziz; Cisneros, Luis; Hardman, Timothy; Harmon, Bryan; Couch, Fergus; Gallagher, Kristalyn; Kilgore, Mark; Wei, Shi; DeMichele, Angela; King, Tari; McAuliffe, Priscilla F.; Nangia, Julie; Lee, Joanna; Tseng, Jennifer; Storniolo, Anna Maria; Thompson, Alastair M.; Gupta, Gaorav P.; Burns, Robyn; Veis, Deborah J.; DeSchryver, Katherine; Zhu, Chunfang; Matusiak, Magdalena; Wang, Jason; Zhu, Shirley X.; Tappenden, Jen; Ding, Daisy Yi; Zhang, Dadong; Luo, Jingqin; Jiang, Shu; Varma, Sushama; Anderson, Lauren; Straub, Cody; Srivastava, Sucheta; Curtis, Christina; Tibshirani , Rob; Angelo, Robert Michael; Hall , Allison; Owzar , Kouros; Polyak , Kornelia; Maley, Carlo; Marks, Jeffrey R.; Colditz, Graham A.; Hwang, E. Shelley; West , Robert B.; Medicine, School of Medicine
    Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We perform multiscale, integrated molecular profiling of DCIS with clinical outcomes by analyzing 774 DCIS samples from 542 patients with 7.3 years median follow-up from the Translational Breast Cancer Research Consortium 038 study and the Resource of Archival Breast Tissue cohorts. We identify 812 genes associated with ipsilateral recurrence within 5 years from treatment and develop a classifier that predicts DCIS or IBC recurrence in both cohorts. Pathways associated with recurrence include proliferation, immune response, and metabolism. Distinct stromal expression patterns and immune cell compositions are identified. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.
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    Racial Differences in the Tumor Immune Landscape and Survival of Women with High-Grade Serous Ovarian Carcinoma
    (American Association for Cancer Research, 2022) Peres, Lauren C.; Colin-Leitzinger, Christelle; Sinha, Sweta; Marks, Jeffrey R.; Conejo-Garcia, Jose R.; Alberg, Anthony J.; Bandera, Elisa V.; Berchuck, Andrew; Bondy, Melissa L.; Christensen, Brock C.; Cote, Michele L.; Doherty, Jennifer Anne; Moorman, Patricia G.; Peters, Edward S.; Segura, Carlos Moran; Nguyen, Jonathan V.; Schwartz, Ann G.; Terry, Paul D.; Wilson, Christopher M.; Fridley, Brooke L.; Schildkraut, Joellen M.; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. Methods: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n = 121 in each racial group). We measured TILs (CD3+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+FoxP3+), myeloid cells (CD11b+), and neutrophils (CD11b+CD15+) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race. Results: Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant. Conclusions: Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC. Impact: This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.