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Estrogen Responsiveness and Control of Normal Human Breast Proliferation

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Abstract

Our understanding of the hormonal control of theproliferation of normal human breast epithelium is stillsurprisingly meager. However, the results of a number ofrecent studies have confirmed that estrogen is the major steroid mitogen for the luminalepithelial cell population (the usual targets forneoplastic transformation). Estrogen seemingly exertsits effects on cell division indirectly as there iscomplete dissociation between the population of luminalepithelial cells expressing the estrogen receptor (ER)4and those that proliferate. We suggest that theER-negative proliferating cells represent a precursor or stem cell population that differentiates toER-containing, nonproliferative cells. In turn, theseER-positive cells act as 'estrogen sensors' and transmitpositive or negative paracrine growth signals to the precursor cells depending on theprevailing hormonal environment.As yetthere is nodirectevidence supporting this hypothesis but we suggestways in which it may be obtained. The implication ofthese studies is that inhibition of luminalepithelial proliferation with tamoxifen or pureantiestrogens or by preventing ovarian steroid secretionshould be an effective strategy for the prevention ofbreast cancer. In addition, we may be able to predictthe risk of breast cancer in an individual by measuringthe intrinsic estrogen sensitivity of her breastepithelium. Finally, study of the paracrine mechanisms of growth control in the normal human breastmay provide new, more specific, therapeutic targets forbreast cancer prevention.

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  1. Elizabeth Anderson
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  2. Robert B. Clarke
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  3. Anthony Howell
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Anderson, E., Clarke, R.B. & Howell, A. Estrogen Responsiveness and Control of Normal Human Breast Proliferation. J Mammary Gland Biol Neoplasia 3, 23–35 (1998). https://doi.org/10.1023/A:1018718117113

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