Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymphnode metastases but without distant metastases (n1-3) in Japan have beenshown to have a 10-year disease-free survival rate of > 60%. It would bereasonable to divide n1-3 Japanese breast cancer patients into groups withhigh- or low-risk for recurrence and to consider post-operative adjuvanttherapy. In the present study, we analyzed 228 consecutive Japanesepatients with n1-3 breast cancer who underwent radical mastectomy and werefollowed up for a median time of 11.0 years. The expression of bcl-2, p53and c-erbB-2 proteins in the primary tumors was examinedimmunohistochemically and their prognostic roles were also analyzed alongwith conventional clinicopathologic indicators. bcl-2 expression wascorrelated with positive estrogen receptor status and inversely correlatedwith p53, c-erbB-2 and histologic grade. Univariate analysis showed thatbcl-2, p53 and c-erbB-2 expression were prognostic indicators of thepatient's group as well as node status, histologic grade, tumor size, ageat diagnosis, menopausal status and estrogen receptor status. Cox'sregression analysis demonstrated that the number of nodes involved,menopausal status, p53 and bcl-2 were independent predictors for overallsurvival and that histologic grade and the number of nodes involved wereindependent predictors for disease-free survival. These results suggestthat bcl-2 expression in combination with p53 and c-erbB-2 expression, thenumber of lymph node metastases, histologic grade and menopausal status areuseful in selecting subgroups of n1-3 breast cancer patients with good orpoor prognoses.