Many studies have indicated that a p53 somatic mutation is an independent poor prognostic indicator for breast cancer (86), with some data suggesting that the prognosis may be influenced by the nature of the mutation (87). Miller et al. (30) have shown that an expression signature for p53 functional status in breast cancer is more predictive of outcome than p53 sequence analysis, and suggest that p53 may be functionally attenuated in the absence of DNA sequence variants. From those data one might assume that the breast cancer in germ line p53 mutation carriers would also carry a poor prognosis; surprisingly little data are available to support that expectation, and the absence of data perhaps speaks loudly. Given that there are no published survival data for breast cancer in p53 mutation carriers, the frequent reports of multiple primary tumors occurring over 10 to 30 years (71) suggest that many of these patients do not succumb to their breast cancer. Unlike BRCA1,2 mutation carriers (88), no distinct pathology or prognosis has been associated with the breast cancer in p53 mutation carriers. In the Hwang et al. (58) series, the overall cancer survival for p53 germ line mutation carriers and controls were not different (Strong et al., unpublished data), suggesting that there is not a uniquely poor prognosis. The relative rarity of p53 germ line mutation carriers will make any distinct positive or negative response to specific agents difficult to determine. Despite the increased radiation sensitivity with respect to increased cancer risk associated with p53 mutations in mouse and human (71,75), no unusual acute toxicities have been described in response to radiation or cytotoxic agents.
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