Johannes D. Veldhuis, MD


March 15, 2000

In This Article

Endocrine Facets of Breast Cancer in Older Women

The incidence of breast cancer rises unidirectionally with age. The National Surgical Adjuvant Breast and Bowel Project compared 13,000 women treated for 5 years with placebo or with tamoxifen. Tamoxifen is a SERM that acts as an estrogen antagonist in breast tissue. Patients in the tamoxifen group achieved a 50% reduction in the cumulative rate of invasive breast cancer.

The estrogen receptor (ER) mediates growth-factor production and possible tumor gene induction in breast cells. Antiestrogens dimerize the ER but stabilize a corepressive (rather than coactivator) state, thereby blocking gene activation. Some of the growth-promoting effects of estrogen are mediated via local IGF-I production and/or the growth-factor receptor family (EGF, c-erbB-2). For example, estrogen requires IGF-I for maximal breast stimulation and stimulates genes involved in IGF-I signaling. Neutralization of IGF-I action by the overexpression of IGF-binding protein limits experimental breast tumor growth. Available clinical data do not relate GH replacement to increased breast cancer incidence.[25]