TP53 has been implicated in regulation of the cell cycle, DNA repair, and
apoptosis. We studied, in primary breast tumors through direct cDNA
sequencing of exons 2-11, whether TP53 gene mutations can predict response
in patients with advanced disease to either first-line tamoxifen therapy
(202 patients, of whom 55% responded) or up-front (poly)chemotherapy (41
patients, of whom 46% responded). TP53 mutations were detected in 90 of
243 (37%) tumors, and one-fourth of these mutations resulted in a
premature termination of the protein. The mutations were observed in 32%
(65 of 202) of the primary tumors of tamoxifen-treated patients and in 61%
(25 of 41) of the primary tumors of the chemotherapy patients. TP53
mutation was significantly associated with a poor response to tamoxifen
[31% versu