Neither estrogen dependence nor clinical response to hormone therapy of the tumor is guaranteed by the mere presence of receptors for estrogens (ERs) or progesterones (PRs). Immunohistochemical staining of ER with polyclonal anti-ER antibodies after in vitro transformation has enabled the identification of two types of defective ER among human breast cancers: those that are unable to bind to the nucleus in a hormone-filled state and those that bind to the nucleus as naked ER. Preliminary clinical correlation studies demonstrate that a subclassification of ER(+) tumors based on functional abnormalities of ER may predict refractoriness to hormone therapy.

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