[Current questions about estrogen receptor determination and hormone dependence (does estrogen receptor positivity...

Exaggerated expectations were raised by estrogen and progesterone receptor determinations introduced in the 1970s for the estimation of hormone dependence. However only two thirds of estrogen and/or progesterone receptor positive cases respond to hormonal therapy. Radioligand binding immuno-assays, and immunohistochemical determinations are wide-spread, however not informative enough. The former two performed on tumor homogenate can not take into account the tissue composition, and heterogeneity of the tumor, and fail to detect receptors of the ligand-saturated forms, while the immunological methods do not give any functional information. There is increased evidence on the existence of dysfunctional estrogen receptor variants. One presents estrogen receptor negative progesterone receptor positive phenotype unable to bind its ligand but constitutively activates its specific DNA-sequence. The other most prevalent in estrogen receptor positive progesterone receptor negative tumors is a mutant "infertile" variant able to hamper normal function of the wild type estrogen receptor by heterodimerization. In order to better utilize estrogen, and progesterone receptor data, propositions are made as following: estrogen receptors from occasionally simultaneously performed biochemical and immunohistochemical determinations should be evaluated in context with other characteristics of the tumor; the detection of mutated defective estrogen receptors may suggest hormone resistance. The correct estimation of the prevalence or lack of hormone dependence is mandatory when systemic treatment-especially in the adjuvant setting is becoming more and more individualized in breast cancer.