P53 PROTEIN OVEREXPRESSION IN RELATION TO RISK-FACTORS FOR BREAST-CANCER

To investigate whether breast tumors developing through a pathway with p53 protein overexpression (p53+) show different risk factor associat ions compared with breast tumors without p53 overexpression (p53-), th e authors determined p53 overexpression in tissue sections of 528 pati ents with invasive breast cancer by using immunohistochemistry. These patients and 918 healthy controls aged 20-54 years participated in a N etherlands population-based case-control study on oral contraceptives in 1986-1989. A total of 142 tumors (27%) demonstrated clear p53 overe xpression (p53+), Most risk factors did not show different association s with p53+ and p53- tumors. However, use of oral contraceptives for 9 or more years was associated with a 2.5-fold increase in the risk of p53+ tumors (95% confidence interval 1.4-4.4; test for trend with mont hs of use, p = 0.01), whereas such use increased the risk of p53- tumo rs only 1.4-fold (95% confidence interval 0.9-2.1;test for trend, p = 0.06). Prolonged lactation (greater than or equal to 25 weeks) was ass ociated with a 40% reduction in risk of p53+ tumors (odds ratio = 0.6; 95% confidence interval 0.3-1.0; test for trend with weeks of lactati on, p = 0.09), whereas the risk of p53- tumors was not associated with lactation. The authors conclude that p53+ and p53- breast tumors are not associated with very distinct risk profiles but that the stronger associations of p53+ tumors with oral contraceptive use and lactation suggest differences in risks that deserve further investigation. If th ese findings can be confirmed and possible molecular mechanisms explor ed, this may help to elucidate the associations between these risk fac tors and breast cancer in general.