Adverse effects of prolactin in rodents and humans: breast and prostate cancer.
Drugs and chemicals shown to induce mammary carcinogenesis in the rat/rodent via prolactin excess have traditionally been argued to pose little or no risk to humans in a regulatory toxicology context. The basis for this assumption is reviewed and placed into context with new evidence in humans that prolactin may be a tumour promoter in the breast and prostate. This evidence includes epidemiology, patient studies involving endocrine evaluation and molecular biology in human cells. It is concluded that hyperprolactinaemia is associated with an increase in breast cancer risk in both post and premenopausal women, that rat carcinogenicity studies are predictive of the human response, and that in a regulatory toxicology context prolactin-induced mammary tumours from nongenotoxic drugs and chemicals are an adverse effect that should not be ignored. More evidence is required concerning prostate cancer risk but molecular biology indicates that prolactin also induces prostate cell proliferation and inhibits apoptosis, which are similar to the responses observed in breast cancer cells.
Harvey
Philip W
PW
Department of Toxicology, Covance Laboratories Ltd., Otley Road, Harrogate, North Yorkshire, UK. philip.harvey@covance.com
Everett
David J
DJ
Springall
Christopher J
CJ
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005260:Female; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000209:etiology* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000378:metabolism; D018570:Risk Assessment
D014150:Antipsychotic Agents; D011388:Prolactin