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c-myc Amplification Is a Better Prognostic Factor than HER2/neu Amplification in Primary Breast Cancer¹

Division of Endocrine Oncology (Department of Medical Oncology) [E. M. J. J. B., J. G. M. K., I. L. v. S., H. P., J. A. F.] and Department of Statistics [W. L. J. v. P.], Dr. Daniel den Hoed Cancer Center, 3008 AE Rotterdam, The Netherlands

Amplification of the c-myc and HER2/neu genes was found in 20 and 23%, respectively, of primary breast cancer tissues derived from 282 patients (median follow-up, 74 months). c-myc amplification was observed more frequently in larger tumors (P = 0.01) and in lymph node-positive patients (P = 0.01) but was not associated with age, menopausal status, or with differentiation grade or steroid receptor status. c-myc amplification was strongly negatively correlated with HER2/neu amplification (P < 0.001). In univariate analysis, amplification of c-myc proved to be a significant predictor of reduced relapse-free and overall survival (for both, P < 0.001). In multivariate analysis for relapse-free survival, c-myc amplification significantly (P = 0.001) added to the prognostic power of tumor size (P < 0.001), lymph node status (P < 0.001), and estrogen receptor status (P = 0.003), with the highest relative failure rate (1.8) after lymph node status (2.2).

In this pilot study, c-myc amplification was predictive for outcome, especially among patients with node-negative disease or steroid receptor-positive tumors; 51 and 46% differences in actuarial 5-year recurrence rates when compared to patients with tumors with normal c-myc gene copy numbers, respectively. HER2/neu amplification was not associated with relapse-free survival but weakly with shorter overall survival in univariate analysis (P = 0.035). Only in the relatively small subgroup of steroid receptor-negative tumors, HER2/neu amplification may identify those patients with an increased risk of death.

In conclusion, amplification of c-myc is an independent powerful prognosticator, particularly in node-negative and steroid receptor-positive breast cancer, whereas HER2/neu amplification may be of limited prognostic value, only in steroid receptor-negative disease.

¹ Supported by grants from the Dutch Cancer Foundation NKB (Grant DDHK 88-9) and Sandoz, Ltd., Basel, Switzerland.

² To whom requests for reprints should be addressed, at Division of Endocrine Oncology, Dr. Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.

Received 9/ 5/91. Accepted 12/13/91.

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