The Tamoxifen Controversy—Clinical Chemopreventive Agent and Experimental Carcinogen

Abstract

While dramatic decreases in the mortality of heart disease, the major fatal disease in the United States, have occurred since 1950, there has been a slight but measurable increase in the cancer mortality rate since 1950 in this country. The reasons for the former precipitous decline in death from heart disease are a balanced combination of prevention and early detection of risk factors combined with improved treatment modalities. While improved treatment modalities of neoplasia have led to significant decreases in certain cancers such as that of testis, Hodgkin's disease, acute lymphatic leukemia in children, and several other cancers, mortality rates from the major cancers, namely lung, breast, prostate, and colon, have either increased or not changed during this period (1). Since the treatment arm of cancer control has not exhibited the dramatic successes seen in, for example, heart disease therapy, many have and are advocating the importance of cancer prevention.

Cancer prevention may be designated as either active or passive (2) in one context or as primary and secondary prevention (3) in another. Avoiding potential carcinogens by quitting smoking, altering diet, and decreasing sunlight exposure are examples of passive or primary prevention. Active or secondary prevention requires patient intervention such as screening, other diagnostic methods for early precancer, or the active administration of agents which inhibit the development of the neoplastic process. This latter field has been termed chemoprevention, a word originally coined by Sporn and Newton in reference to the effect of retinoids in preventing experimental neoplasia (4). Since that time the application of chemoprevention has been extended to a number of human clinical trials using a variety of agents for the chemoprevention of a number of different types of neoplasms (5).