دورية أكاديمية
Impact of obesity on breast cancer recurrence and minimal residual disease.
العنوان: | Impact of obesity on breast cancer recurrence and minimal residual disease. |
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المؤلفون: | Ecker BL; Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Lee JY; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Sterner CJ; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Solomon AC; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Pant DK; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Shen F; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Peraza J; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Vaught L; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Mahendra S; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Belka GK; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Pan TC; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA., Schmitz KH; Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA, 17033, USA., Chodosh LA; Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. chodosh@pennmedicine.upenn.edu.; 2-PREVENT Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. chodosh@pennmedicine.upenn.edu.; The Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6160, USA. chodosh@pennmedicine.upenn.edu. |
المصدر: | Breast cancer research : BCR [Breast Cancer Res] 2019 Mar 13; Vol. 21 (1), pp. 41. Date of Electronic Publication: 2019 Mar 13. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 100927353 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-542X (Electronic) Linking ISSN: 14655411 NLM ISO Abbreviation: Breast Cancer Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: London, UK : BioMed Central Ltd Original Publication: London, UK : Current Science, c1999- |
مواضيع طبية MeSH: | Breast Neoplasms/*mortality , Mammary Neoplasms, Experimental/*pathology , Neoplasm Recurrence, Local/*pathology , Obesity/*pathology, Animals ; Body Mass Index ; Body Weight ; Breast Neoplasms/pathology ; Cell Line, Tumor/transplantation ; Datasets as Topic ; Diet, High-Fat/adverse effects ; Disease-Free Survival ; Female ; Humans ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/mortality ; Mice, Obese ; Mice, Transgenic ; Neoplasm Recurrence, Local/mortality ; Neoplasm, Residual ; Obesity/etiology ; Receptor, ErbB-2/genetics ; Survival Analysis |
مستخلص: | Background: Obesity is associated with an increased risk of breast cancer recurrence and cancer death. Recurrent cancers arise from the pool of residual tumor cells, or minimal residual disease (MRD), that survives primary treatment and persists in the host. Whether the association of obesity with recurrence risk is causal is unknown, and the impact of obesity on MRD and breast cancer recurrence has not been reported in humans or in animal models. Methods: Doxycycline-inducible primary mammary tumors were generated in intact MMTV-rtTA;TetO-HER2/neu (MTB/TAN) mice or orthotopic recipients fed a high-fat diet (HFD; 60% kcal from fat) or a control low-fat diet (LFD; 10% kcal from fat). Following oncogene downregulation and tumor regression, mice were followed for clinical recurrence. Body weight was measured twice weekly and used to segregate HFD mice into obese (i.e., responders) and lean (i.e., nonresponders) study arms, and obesity was correlated with body fat percentage, glucose tolerance (measured using intraperitoneal glucose tolerance tests), serum biomarkers (measured by enzyme-linked immunosorbent assay), and tissue transcriptomics (assessed by RNA sequencing). MRD was quantified by droplet digital PCR. Results: HFD-Obese mice weighed significantly more than HFD-Lean and LFD control mice (p < 0.001) and had increased body fat percentage (p < 0.001). Obese mice exhibited fasting hyperglycemia, hyperinsulinemia, and impaired glucose tolerance, as well as decreased serum levels of adiponectin and increased levels of leptin, resistin, and insulin-like growth factor 1. Tumor recurrence was accelerated in HFD-Obese mice compared with HFD-Lean and LFD control mice (median relapse-free survival 53.0 days vs. 87.0 days vs. 80.0 days, log-rank p < 0.001; HFD-Obese compared with HFD-Lean HR 2.52, 95% CI 1.52-4.16; HFD-Obese compared with LFD HR 2.27, 95% CI 1.42-3.63). HFD-Obese mice harbored a significantly greater number of residual tumor cells than HFD-Lean and LFD mice (12,550 ± 991 vs. 7339 ± 2182 vs. 4793 ± 1618 cells, p < 0.001). Conclusion: These studies provide a genetically engineered mouse model for study of the association of diet-induced obesity with breast cancer recurrence. They demonstrate that this model recapitulates physiological changes characteristic of obese patients, establish that the association between obesity and recurrence risk is causal in nature, and suggest that obesity is associated with the increased survival and persistence of residual tumor cells. |
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معلومات مُعتمدة: | R01 CA098371 United States CA NCI NIH HHS; R01 CA148774 United States CA NCI NIH HHS; U54 CA155850 United States CA NCI NIH HHS; R01 CA143296 United States CA NCI NIH HHS; R01 CA208273 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: Breast cancer; High-fat diet; Obesity; Recurrence; Tumor dormancy |
المشرفين على المادة: | EC 2.7.10.1 (ERBB2 protein, human) EC 2.7.10.1 (Receptor, ErbB-2) |
تواريخ الأحداث: | Date Created: 20190315 Date Completed: 20190722 Latest Revision: 20230930 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC6416940 |
DOI: | 10.1186/s13058-018-1087-7 |
PMID: | 30867005 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1465-542X |
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DOI: | 10.1186/s13058-018-1087-7 |