THE ROLE AND PROGNOSTIC-SIGNIFICANCE OF P53 GENE ALTERATIONS IN BREAST-CANCER

Alterations in the p53 tumor suppressor gene are the most frequent genetic changes found in breast cancer, with an incidence reported in a range of 15 to 50%. The incidence of p53 alterations is approximately 15% for in situ carcinoma, while for invasive node-positive disease it is 2 to 3 times higher. This high rate of alteration suggests that the gene plays a central role in the development of breast cancer. The p53 gene functions as a negative regulator of cell growth. Alterations in the gene lead to loss of its usual negative growth regulation and more rapid cell proliferation. Since p53 alteration can reflect a more advanced state of progression and a higher rate of proliferation, breast tumors that have a p53 alteration could have a greater probability of having micrometastasis. p53 alterations could therefore be a prognostic factor for recurrence after primary local therapy. Consistent with this hypothesis, several independent studies using different methodologies have found that breast tumors with altered p53 have a worse prognosis and are also more likely to have other poor prognostic factors.