Re: Effect of Epidermal Growth Factor Receptor Inhibitor on Development of Estrogen Receptor–Negative Mammary Tumors

Extract

In the prevention of breast carcinoma, any new drug capable of inhibiting the onset of breast carcinoma will offer new opportunities to fight this disease. Data from Lu et al. (1) suggested that treatment with ZD1839 (an anti–epidermal growth factor [EGF]-receptor tyrosine-kinase inhibitor) to prevent hormone-independent breast carcinomas might be complementary to established antihormonal treatments. However, some considerations must be pointed out before conclusions can be extrapolated to the prevention of human tumors. In the MMTV-rat HER2/neu proto-oncogene transgenic mice model, any treatment that reduces mammary gland development, including vaccination against HER2/neu (2), has been shown to prevent or delay tumor onset by reducing the number of cells at risk of transformation. Accordingly, we found that even tamoxifen, in the same transgenic model, prevented the onset of mammary tumors, even though they were hormone receptor–negative tumors, by reducing the number of mammary alveoli (3). These results clearly contrast with observations obtained with tamoxifen in clinical trials that showed no effect on estrogen receptor–negative tumors, and thus indicate that the response of normal mammary tissue to drugs vary between transgenic mice and humans.