Estrogen Receptors and Breast Cancer

The literature indicates that relationships between epidemiologic variables and estrogen receptor activity are not clearly defined. Conflicting and unconfirmed results have been published. Most studies have been based on clinical case series rather than on carefully conducted population-based epidemiologic investigations. In addition, previous reports have not generally considered the potential role of confounding and interaction in the interpretation of the associations reported between estrogen receptor status and risk factors for breast cancer. Given these considerations, the need for further research in this area is obvious. Application of an estrogen receptor scheme (positive vs. negative) for defining breast cancer may allow delineation of cases that may appear quite similar but that represent two different types of disease. Estrogen receptor-positive and estrogen receptor-negative breast cancer behave differently biologically, have different treatment and prognostic implications, and thus may also possibly have different risk factor patterns. Moreover, the extent to which receptor status reflects effects associated with exposure, the disease process, or host influences is not clearly understood. There is some evidence that estrophilin is a biochemical marker of tumor differentiation. Moolgavkar et al. suggested that all breast cancers are initially estrogen receptor-positive, but that as the tumor undergoes clonal evolution and becomes more undifferentiated, the ability to express estrophilin is lost in some cases. If this is true, estrogen receptor results may reflect temporal changes in the biologic characteristics of the tumor as it progresses from a well differentiated to a poorly differentiated state. Receptor status could also reflect changes in host resistance and tumor aggressiveness. This concept is consistent with previous observations that anaplastic, rapidly growing cancers are less likely to be receptor-positive. It has not been established whether estrogen receptor-negative tumors represent an advanced stage of the disease or arise de novo. Clinical studies have failed to demonstrate a relationship between extent of disease at diagnosis and receptor results. Estrophilin concentrations also are apparently not related to stage of disease, lending no support for the notion that receptor level declines with progression of the disease. It is possible that certain etiologic factors lead to the natural selection and growth of receptor-negative cells and that receptor negativity is an early, inherent characteristic of some breast cancers.(ABSTRACT TRUNCATED AT 400 WORDS)