Download Hypothesis - MULTIWEBCAST

High-density lipoprotein and very-low-density
lipoprotein have opposing roles in regulating
tumor-initiating cells and sensitivity to radiation
in inflammatory breast cancer
Adam R. Wolfe, Rachel L. Atkinson, Jay Reddy, Bisrat G. Debeb,
Bradley J. Atkinson, Naoto T. Ueno, and Wendy A. Woodward
Department of Radiation Oncology, The University of Texas MD
Anderson Cancer Center, Houston, Texas
Background
• Epidemiological and animal studies have
revealed an association between dietary
cholesterol and the incidence of breast cancer. 1
• Statin use significantly improves local control
after IBC PMRT.
• Simvastatin significantly radiosensitizes across
triple-negative and IBC cell lines of multiple
subtypes. 2
Hypothesis
• Direct manipulation of lipoproteins will
reproduce the findings previously reported
with statin treatment with respect to selfrenewal, radiosensitization in vitro and clinical
outcomes in IBC patients.
HDL radiosensitized and decreased DNA repair
following radiation: VLDL showed reversed results
Dyslipidemia in IBC patients predicts outcomes
Conclusions
• Our results demonstrate a role for
dyslipidemia in radiation sensitivity and
survival among IBC patients.
• Benefit of aggressively correcting dyslipidemia
in IBC patients at the time of diagnosis and
altering lipid profiles in IBC patients without
clinical dyslipidemia remains to be tested.
References
• 1. Kritchevsky SB, Kritchevsky D: Serum
cholesterol and cancer risk: an epidemiologic
perspective. Annu Rev Nutr 1992, 12:391–416.
• 2. Lacerda, et al. Simvastatin Radiosensitizes
Differentiated and Stem-Like Breast Cancer Cell
Lines and Is Associated With Improved Local
Control in Inflammatory Breast Cancer Patients
Treated With Postmastectomy Radiation. Stem
Cells Trans Med 2014; 3:849-856