Neuroleptic-induced prolactin level elevation and breast cancer: an emerging clinical issue

This article reviews the evidence that neuroleptics may increase the risk of breast cancer via their effects on prolactin secretion. All available neuroleptics, including reserpine, raise serum prolactin levels. Elevated serum prolactin level increases the incidence of spontaneously occurring mammary tumors in mice, and increases the growth of established carcinogen-induced mammary tumors in rats. Caution is necessary in extrapolating this relationship to human mammary tumors because human and rodent tumors differ in some important characteristics, including hormone responsiveness. Serum prolactin levels in women with, or at risk for, breast cancer have generally been normal, and only a minority of human mammary tumors respond to changes in serum prolactin levels. Epidemiologic studies have failed to demonstrate an increased risk of breast cancer associated with the use of neuroleptics or reserpine. Thus, although some human mammary tumors are prolactin dependent, the available evidence does not demonstrate an increased risk of breast cancer in women receiving neuroleptics. We conclude that (1) additional epidemiologic studies of the incidence of mammary tumors in women treated with neuroleptics are desirable; (2) it is premature to mandate warning patients of an unknown and undemonstrated increase in the risk of developing breast cancer associated with neuroleptic treatment; (3) detection of existing mammary tumors by breast examination prior to administration of neuroleptics is desirable; and (4) development of antipsychotic drugs that do not increase serum prolactin level may be indicated.