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HER-2/neu Amplification Predicts Poor Survival in Node-positive Breast Cancer¹

Southern Swedish Breast Cancer Study Group, Department of Oncology, University Hospital, S-221 85 Lund, Sweden [Å. B., H. S., M. F., D. K.], and Department of Medicine/Oncology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7884

HER-2/neu protooncogene amplification and protein expression were analyzed with slot blot and Western blot techniques, respectively, in more than 300 invasive primary breast tumors of all stages. Amplification (2- <30 copies) was found in 17% of these tumors and high expression was seen in 19%. There was a striking coincidence between gene amplification and high expression. Tumors associated with many involved axillary lymph nodes or with Stage IV disease were more often HER-2/neu amplified or overexpressed. Furthermore, gene alteration was strongly correlated with the absence of steroid receptors and with larger tumor size. High expression without gene amplification was seen in a minor subset of tumors of less aggressive character. Neither amplification nor overexpression was correlated with disease outcome for patients with negative axillary lymph nodes. For node-positive patients, however, HER-2/neu amplification was a significant predictor of early relapse and death (median follow-up = 45 months), and a similar trend, although not significant, existed for high gene expression. Multivariate analyses indicated that HER-2/neu alterations were not independent predictors of patient outcome.

¹ Supported in part by Fru Berta Kamprads Foundation, John and Augusta Perssons Foundation, Swedish Cancer Society, NIH Grant CA 30195, and American Cancer Society Grant IN-11;61.

² To whom reprint requests should be addressed.

Received 12/ 5/89. Revised 3/21/90.

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