Breast cancer prevention.
We have developed a new approach for breast cancer prevention, capitalizing in the preventive effect of early first full-term pregnancy, hormonally induced differentiation and our ability to identify specific genomic signatures that allow us to predict risk reduction. Early pregnancy imprints in the breast permanent genomic changes or a 'signature' that reduces the susceptibility of this organ to cancer. At cellular level, what we have achieved is the shifting of the Stem Cell 1 population, highly susceptible to cancer, to a population of Stem Cell 2 that is refractory to carcinogenesis. In a case-control study, we have compared the gene expression profile in normal breast tissue from nulliparous and parous postmenopausal women with (case) and without (control) breast cancer. We have determined that early first full-term pregnancy induces a specific genomic signature in the postmenopausal breast that is the biomarker for the Stem cell 2. The Stem cell 2 contains specific genes controlling transcription, RNA processing, immune response, apoptosis and DNA repair. We have further detected in the plasma, using an ELISA assay, the proteins coded by the gene signature. We are developing clinical trials to demonstrate the proof of the principle that r-hCG can induce in the human breast a genomic signature of the Stem cell 2. This is a concept that challenges the currently available chemopreventive agents that need to be given for extended periods for maintaining the suppression of a specific metabolic pathway or the abrogation of the function of an organ.
Russo
J
J
Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA.
Balogh
G
G
Russo
I H
IH
D001940:Breast / Q000166:cytology* / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology; D010298:Parity; D017698:Postmenopause; D011247:Pregnancy; D012313:RNA; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells
D012313:RNA