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Chemopreventive Effects of Berries and Berry Components in Animal Models: Prevention of Estrogen-Mediated Mammary Tumors in ACI Rats by Berries

  • Harini Aiyer
  • Srivani Ravoori
  • Ramesh Gupta
Chapter

Abstract

Breast cancer is the most commonly diagnosed and the most prevalent cancer among women worldwide. There are several million women who could potentially benefit from prevention of both primary and recurring breast tumors. The female reproductive hormone 17ß-estradiol (E2) has been implicated as a causative agent in breast cancer. ACI rats are susceptible to mammary adenocarcinomas induced by physiological levels of E2, making it a preclinical model with a high applicability for clinical translation. We have shown that diets supplemented with blueberry or black raspberry (1, 2.5 and 5% w/w) show significant reduction in the latency, incidence, number, and volume of tumors in this animal model of E2-mediated mammary tumorigenesis. Berry phytochemicals provide this protection by modulating E2-metabolizing enzymes, preventing DNA damage, increasing DNA repair, reducing E2-induced cell proliferation, lowering the levels of circulating prolactin, and by eliciting an anti-estrogenic effect. Further, upon conversion of effective rodent doses to human equivalents using allometry, it was found that a woman with an average caloric intake of 2,000 kcal/day may require only 1/2 to 1 cup of fresh or frozen berries to achieve significant protection against the risk posed by E2. This dose can be effectively applied in a community setting to achieve primary prevention as well as in a clinical setting to prevent recurrence.

Keywords

Hormonal breast cancer ACI rat model Prevention Blueberry Black raspberry Ellagic acid allometric scaling 

Notes

Acknowledgment

The authors would like to acknowledge Dr. Manicka V. Vadhanam for support during the initial studies using the ACI rat model in the laboratory. This research was supported by NIH grants CA-118114, CA-90892, and CA-92758 and Agnes Brown Duggan Endowment. Dr. Harini S. Aiyer was a graduate student of Dr. Ramesh Gupta when she conducted a large part of the berry intervention studies described here. Dr. Ramesh Gupta holds the Agnes Brown Duggan Chair in Oncological Research.

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© Springer New York 2011

Authors and Affiliations

  1. 1.James Graham Brown Cancer Center, University of LouisvilleLouisvilleUSA
  2. 2.Department of SurgeryUniversity of LouisvilleLouisvilleUSA
  3. 3.Department of Pharmacology and ToxicologyUniversity of LouisvilleLouisvilleUSA

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