VOL. 1, No. 1, January 2004

J. Russo and I. H. Russo [2004] Med Hypotheses Res 1: 11-22.

A New Paradigm in Breast Cancer Prevention

Jose Russo* and Irma H. Russo

Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111,

Abstract. The incurability of breast cancer, in association with a world-wide increase
in its incidence, indicates that primary prevention is the ultimate goal for breast cancer
control. It is in this stage of knowledge that we have developed a new paradigm for breast
cancer prevention. Our paradigm has emerged from epidemiological observations of a
direct association of breast cancer risk with nulliparity and of protection conferred by an
early first full term pregnancy. We have chosen this specific strategy because it is a window
of opportunity that nature has provided us for learning how a physiological event
produces in a significant percentage of women a complete protection against cancer. Our
studies have unraveled the biological principle underlying the protection conferred by an
early first full-term pregnancy. Furthermore, we have also demonstrated that the same
degree of protection can be elicited by a short treatment with recombinant human
chorionic gonadotropin (r-hCG), a hormone secreted during pregnancy. Both pregnancy
and r-hCG treatment induce in the breast the expression of a specific genomic-proteomic
signature that results from the completion of this organ’s differentiation. R-hCG also
inhibits the progression of early lesions, such as intraductal proliferations, and carcinomas
in situ and the regression of established tumors. These observations indicate that r-hCG
administered for a very short period of time has significant potential as a chemopreventive
agent, protecting the normal cell from becoming malignant. This new biological concept
also implies that when the genomic signature of protection or refractoriness to
carcinogenesis is acquired, the hormonal treatment with r-hCG is no longer necessary.
This is a novel approach that challenges the current concept that a chemopreventive agent
needs to be given for a long period to suppress a metabolic pathway or abrogate the
function of an organ.

*Address all correspondence to: Dr. Jose Russo, Breast Cancer Research Laboratory, Fox
Chase Cancer Center, 3233 Cottman Avenue, Philadelphia, PA 19111 (USA).
Phone: 215-728-4782; Fax: 215-728-2180; E-Mail:

Full Text [PDF]