Germ-line HER-2 variant and breast cancer risk by stage of disease

HER-2 gene amplification and protein overexpression has been associated wit h increased risk of advanced-stage breast cancer and poor prognosis. Recent ly, a single missense point mutation (Ile(655)Val) in the transmembrane dom ain of the HER-2 gene was associated with a 40% increase in breast cancer r isk among women 45 years of age and younger. In this analysis, we measured the association between the Ile(655)Val variant and postmenopausal breast c ancer among women participating in the Hawaii and Los Angeles Multiethnic C ohort. Risk of localized breast cancer was significantly elevated among wom en with the HER-2 variant, but not among women with regional or metastatic disease. Women with at least one copy of the Valine variant were approximat ely one-half as likely to have high-stage as low-stage breast cancer (P = . 02), and this effect was present across racial/ethnic groups.