Abstract
BackgroundInflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene.MethodsThe effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed.ResultsRats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis.ConclusionOur data suggests that systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer.
Highlights
Inflammation has been linked to the etiology of many organ-specific cancers
Adjuvant treatment increases incidence of mammary carcinomas following infusion of activated neu Direct transfer of the neu oncogene into the mammary ductal cells results in clonal development of mammary carcinomas (Figure 1A and 1B) [12,13]. This model provides a unique system to assess the effects of chronic inflammation on breast cancer development
There were no histopathological differences between mammary carcinomas arising in the various treatment groups
Summary
Indirect evidence suggests a possible role for inflammation in breast cancer. The etiology of breast cancer involves the interaction of inherited risk with environmental exposure. 30% of breast cancer risk is inherited [1], the majority of which is controlled by modifier genetic elements individually having low genetic penetrance, but high population frequencies [2]. Our knowledge of environmental factors that modulate breast cancer risk is quite incomplete. The best documented association is for ionizing radiation, which carries the highest risk for breast cancer when exposure occurs prior to adulthood [3]. Chronic inflammation arising from a variety of environmental and infectious sources is associated with promotion of many cancer types [5]. Evidence for chronic inflammation in breast cancer etiology is supported by (page number not for citation purposes)
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