Freund's vaccine adjuvant promotes Her2/neu breast cancer.
BACKGROUND
Inflammation 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.


METHODS
The 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.


RESULTS
Rats 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.


CONCLUSIONS
Our 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.
Cotroneo
Michelle S
MS
McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI, USA. cotroneoms@yahoo.com
Haag
Jill D
JD
Stapel
Nicholas R
NR
Waller
Jordy L
JL
Woditschka
Stephan
S
Gould
Michael N
MN
D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects*; D018734:Genes, erbB-2 / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000139:chemically induced* / Q000150:complications*
D000276:Adjuvants, Immunologic; D005620:Freund's Adjuvant