Can expression of apoptosis genes, bcl-2 and bax, predict survival and responsiveness to chemotherapy in node-negative breast cancer patients?

Background. Although the status of the axillary lymph nodes is widely accep ted to be associated with prognosis in breast cancer patients, there is a n eed for biomarkers to be analyzed as indicators of responsiveness to treatm ent. The objective of this study was to test the hypothesis that the expres sion of apoptosis genes, bcl-2 and bax, predicts survival and responsivenes s to chemotherapy in node-negative breast cancer patients. Methods. One hundred thirty premenopausal women with primary breast carcino ma were studied for the expression of bcl-2 and bax genes. The relationship between the expression of bcl-2 and bax proteins and a series of markers o f known prognostic value [such as tumor size, nuclear grade, receptors of t he steroid hormones estrogen (ER) and progesterone (PgR)]. The association of these proteins with survival and responsiveness to chemotherapy was also examined. Results. Sixty (46%) and sixty-four (49%) breast cancer cases were found po sitive for bcl-2 and bax, respectively, as indicated by immunohistochemistr y. A statistically significant association was found between expression of bcl-2 and tumor size (P = 0.001), low grade (grade I) (P = 0.002), positivi ty of ER (P = 0.001), positivity of PR (P = 0.03), and superior disease-fre e survival (DFS) (P = 0.04), and superior overall survival (OS) (P = 0.03). In contrast, no similar associations were observed for the bax gene. Overa ll, there was a trend toward an association between adjuvant chemotherapy a nd DFS (P = 0.08) and OS (P = 0.07). This trend became statistically signif icant when the patients were analyzed by individual gene expression. In bax -positive patients, chemotherapy improves 6-year DFS (P = 0.01) and OS (P = 0.03) while similar effects were not observed in the other subgroups of pa tients. Conclusion. Our results indicated that bcl-2 expression is associated with a number of favorable prognostic factors and better clinical outcome, while bax expression seems to have positive predictive value for responsiveness to chemotherapy in lymph node-negative breast cancer patients. (C) 2001 Aca demic Press.