Both
estrogen and
insulin-like growth factor-1 (
IGF-I) are critical for normal mammary gland development, but are also implicated in
breast cancer development and progression. Evidence that the signaling pathways utilized by these
hormones interact has been shown in normal and tumorigenic cell lines, xenograft models, and
breast cancer tissue. Analysis of the mechanism of interaction between
estrogen and
IGF-I has revealed multiple levels of cross-talk with bi-directional regulation of both pathways. Importantly, this bi-directional regulation is often in a positive manner and the resulting synergism noted between these two potent
mitogens may be a critical
element in the progression of
breast cancer. While targeting of the
estrogen receptor has shown success in the prevention and treatment of
breast cancer, it is hoped that targeting of the IGF signaling pathway will yield similar beneficial results and that inhibitors of IGF signaling may be particularly useful in combination with current
antiestrogen therapies. This review will focus on the evidence indicating cross-talk between
estrogen and
IGF-I and reveal some of the complex mechanisms that link these important pathways in
breast cancer.