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Influence of Antibiotic Treatment on Breast Carcinoma Development in Proto-neu Transgenic Mice

¹ Molecular Targeting Unit, Medicine Laboratory Unit, and Unit of Medical Statistics and Biometry, Department of Experimental Oncology and Laboratories, National Cancer Institute; ² Department of Human Morphology and ³ Institute of Pathology, University of Milan, Milan, Italy

Requests for reprints: Andrea Balsari, Institute of Pathology, University of Milan, Via Mangiagalli, 31, Milan, Italy. Phone: 39-02-23902564; E-mail: andrea.balsari{at}unimi.it.

The effect of prolonged antibiotic treatments on tumor development was evaluated in proto-neu transgenic mice, which spontaneously develop mammary carcinomas. Virgin transgenic mice were treated with metronidazole/ciprofloxacin or gentamicin through the drinking water. The hazard ratio [HR; 95% confidence interval (95% CI)] of breast cancer occurrence in metronidazole/ciprofloxacin-treated mice was more than triple that for controls [3.11 (1.13-8.53); P = 0.028], whereas only a slight increase in HR (95% CI) was observed in gentamicin-treated mice [1.39 (0.56-3.47); P = 0.481]. Tumor growth rate in gentamicin-treated mice was significantly faster than in untreated control mice (P = 0.043). Moreover, mammary glands from mice treated with either antibiotic regimen showed increased lobulization, with more numerous and more developed terminal ductal lobular units than in controls. These results indicate that prolonged exposure to relevant doses of antibiotics affects the mammary glands in this particular model of HER-2/neu transgenic mice; further studies to understand the precise mechanism by which antibiotic treatments influence mammary gland differentiation are critical. (Cancer Res 2006; (12): 6219-24)

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