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Item Author Correction: Upregulation of lipid metabolism genes in the breast prior to cancer diagnosis(Springer Nature, 2024-06-17) Marino, Natascia; German, Rana; Rao, Xi; Simpson, Ed; Liu, Sheng; Wan, Jun; Liu, Yunlong; Sandusky, George; Jacobsen, Max; Stovall, Miranda; Cao, Sha; Storniolo, Anna Maria V.; Medicine, School of MedicineCorrection to: npj Breast Cancer 10.1038/s41523-020-00191-8, published online 06 October 2020 In this article, the author name Miranda Stovall was incorrectly written as Miranda Stoval. The original article has been corrected.Item Disparities in outcomes among patients diagnosed with cancer in proximity to an emergency department visit(Springer, 2022-06-23) Pettit, Nicholas; Sarmiento, Elisa; Kline, Jeffrey; Emergency Medicine, School of MedicineA suspected diagnosis of cancer in the emergency department (ED) may be associated with poor outcomes, related to health disparities, however data are limited. This is a retrospective observational cohort of the Indiana State Department of Health Cancer Registry, and the Indiana Network for Patient Care. First time cancer diagnoses appearing in the registry between January 2013 and December 2017 were included. Cases identified as patients who had an ED visit in the 6 months before their cancer diagnosis; controls had no preceding ED visits. The primary outcome was mortality, comparing ED-associated mortality to non-ED-associated. 134,761 first-time cancer patients were identified, including 15,432 (11.5%) cases. The mean age was same at 65, more of the cases were Black than the controls (12.4% vs 7.4%, P < .0001) and more were low income (36.4%. vs 29.3%). The top 3 ED-associated cancer diagnoses were lung (18.4%), breast (8.9%), and colorectal cancers (8.9%), whereas the controls were breast (17%), lung (14.9%), and prostate cancers (10.1%). Cases observed an over three-fold higher mortality, with cumulative death rate of 32.9% for cases vs 9.0% for controls (P < .0001). Regression analysis predicting mortality, controlling for many confounders produced an odds ratio of 4.12 (95% CI 3.72–4.56 for cases). This study found that an ED visit within 6 months prior to the first time of ICD-coded cancer is associated with Black race, low income and an overall three-fold increased adjusted risk of death. The mortality rates for ED-associated cancers are uniformly worse for all cancer types. These data suggest that additional work is needed to reduce disparities among ED-associated cancer diagnoses.Item Risk of hematologic malignancies after breast ductal carcinoma in situ treatment with ionizing radiation(Springer Nature, 2021-03-02) Wang, Kang; Li, Zhuyue; Chen, Xingxing; Zhang, Jianjun; Xiong, Yongfu; Zhong, Guochao; Shi, Yang; Li, Qing; Zhang, Xiang; Li, Hongyuan; Xiang, Tingxiu; Foukakis, Theodoros; Radivoyevitch, Tomas; Ren, Guosheng; Epidemiology, School of Public HealthThe increased incidence of secondary hematologic malignancies (SHM) is a well-known, potentially fatal, complication after cancer treatment. It is unknown if patients with ductal carcinoma in situ (DCIS) of the breast treated with external beam radiotherapy (RT) and who survive long-term have increased risks of secondary hematologic malignancies (SHM), especially for low/intermediate-risk subsets with limited benefits from RT. DCIS patients in Surveillance, Epidemiology, and End Results (SEER) registries (1975–2016) were identified. Relative risks (RR), hazard ratio (HR), and standardized incidence ratios (SIR) were calculated to assess the SHM risk and subsequent survival times. SHM development, defined as a nonsynchronous SHM occurring ≥1 year after DCIS diagnosis, was our primary endpoint. Of 184,363 eligible patients with DCIS, 77,927 (42.3%) in the RT group, and 106,436 (57.7%) in the non-RT group, 1289 developed SHMs a median of 6.4 years (interquartile range, 3.5 to 10.3 years) after their DCIS diagnosis. Compared with DCIS patients in the non-RT group, RT was associated with increased early risk of developing acute lymphoblastic leukemia (ALL; hazard ratio, 3.15; 95% CI, 1.21 to 8.17; P = 0.02), and a delayed risk of non-Hodgkin lymphoma (NHL; hazard ratio, 1.33; 95% CI, 1.09 to 1.62; P < 0.001). This increased risk of ALL and NHL after RT was also observed in subgroup analyses restricted to low/intermediate-risk DCIS. In summary, our data suggest that RT after breast conserving surgery for DCIS patients should be cautiously tailored, especially for low and intermediate-risk patients. Long-term SHM surveillance after DCIS diagnosis is warranted.Item Upregulation of lipid metabolism genes in the breast prior to cancer diagnosis(Nature Publishing Group, 2020-10-06) Marino, Natascia; German, Rana; Rao, Xi; Simpson, Ed; Liu, Sheng; Wan, Jun; Liu, Yunlong; Sandusky, George; Jacobsen, Max; Stoval, Miranda; Cao, Sha; Storniolo, Anna Maria V.; Medicine, School of MedicineHistologically normal tissue adjacent to the tumor can provide insight of the microenvironmental alterations surrounding the cancerous lesion and affecting the progression of the disease. However, little is known about the molecular changes governing cancer initiation in cancer-free breast tissue. Here, we employed laser microdissection and whole-transcriptome profiling of the breast epithelium prior to and post tumor diagnosis to identify the earliest alterations in breast carcinogenesis. Furthermore, a comprehensive analysis of the three tissue compartments (microdissected epithelium, stroma, and adipose tissue) was performed on the breast donated by either healthy subjects or women prior to the clinical manifestation of cancer (labeled “susceptible normal tissue”). Although both susceptible and healthy breast tissues appeared histologically normal, the susceptible breast epithelium displayed a significant upregulation of genes involved in fatty acid uptake/transport (CD36 and AQP7), lipolysis (LIPE), and lipid peroxidation (AKR1C1). Upregulation of lipid metabolism- and fatty acid transport-related genes was observed also in the microdissected susceptible stromal and adipose tissue compartments, respectively, when compared with the matched healthy controls. Moreover, inter-compartmental co-expression analysis showed increased epithelium-adipose tissue crosstalk in the susceptible breasts as compared with healthy controls. Interestingly, reductions in natural killer (NK)-related gene signature and CD45+/CD20+ cell staining were also observed in the stromal compartment of susceptible breasts. Our study yields new insights into the cancer initiation process in the breast. The data suggest that in the early phase of cancer development, metabolic activation of the breast, together with increased epithelium-adipose tissue crosstalk may create a favorable environment for final cell transformation, proliferation, and survival.