ONCOGENE AMPLIFICATION AND PROGNOSIS IN BREAST-CANCER - RELATIONSHIP WITH SYSTEMIC TREATMENT

In the present study, we aimed to clarify the potential of oncogene amplifications as markers for the prediction of (i) (relapse-free) survival, (ii) response to first-line endocrine therapy and (iii) subsequent chemotherapy in patients with recurrent breast cancer. To attain this goal, amplification of different oncogenes (HER-2/neu, c-MYC and INT-2) was studied in primary tumors of a series of 259 patients with breast cancer (median follow-up of 72 mo). Of these tumors, 49.8% did not contain an amplification of any of the oncogenes studied, whereas in the amplified subgroup, INT-2 was amplified in 13%, HER-2/neu in 24% and c-MYC in 20% of the tumors. In univariate analysis, INT-2 amplification was associated with an increased risk of relapse (p<0.03), especially in the subgroups of 85 node-negative (p=0.05) and 156 ER/PgR-positive patients (p=0.01). Cox multivariate regression analysis showed that c-MYC was the only oncogene whose amplification was significantly related with the rate of relapse. With respect to amplification in patients developing metastatic disease, who received first-line hormonal therapy (n=114), HER-2/neu amplification was associated with a less favorable response to endocrine therapy (objective response rate only 17% and a progression-free survival (PFS) of only 4% at 12 mo). Interestingly, distinct INT-2 amplification might predict abetter response to endocrine therapy (objective response rate of 56%, and a PFS after relapse of 42% at 12 mo). After failure of hormonal therapy, ensuing chemotherapy caused a prolonged PFS of 287 days vs. 90 days for those patients whose tumors showed HER-2/neu amplification vs. those without HER-2/neu amplification. We conclude that-oncogene amplification is related to relapse-free survival (RFS), response to systemic therapy, and to overall survival with different outcomes for the respective oncogenes. Simultaneous determination of these oncogenes may be of importance with respect to both selection of patients at high risk for recurrence and for selection of a particular type of therapy.