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 self-renewal, 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