Slamon 1987: HER2 gene amplification marks an aggressive form of breast cancer
Extra copies of the HER2 gene were found in about a quarter to a third of breast cancers and picked out the patients most likely to relapse, the discovery that made HER2 a drug target and a test.
Overview
Slamon and colleagues measured copies of the HER2/neu gene in 189 primary human breast cancers and found amplification in 53 of them, about 28%, with amplification ranging from 2- to more than 20-fold. In node-positive patients, amplification was a strong and independent predictor of both time to relapse and survival, stronger than most conventional factors. The paper established HER2 as a marker of aggressive disease and, with later work showing the receptor's role in growth signalling, as the target that trastuzumab would hit a decade later.
- HER2/neu amplification in 53 of 189 primary breast cancers (about 28%).
- Amplification correlated with the number of positive lymph nodes and, in node-positive patients, with shorter time to relapse and shorter survival.
- Amplification was an independent prognostic factor in multivariate analysis, stronger than tumour size or hormone receptor status.
Every HER2 test, every trastuzumab prescription and the whole HER2-positive breast cancer category trace back to this observation. It is the model for how a genomic marker of bad prognosis became a drug target and then the basis for one of the largest survival gains in solid tumour oncology.
- Prognostic effect was clearest in node-positive disease; the node-negative signal was weaker in this dataset.
- Measured gene copies by Southern blot; clinical testing later moved to immunohistochemistry and in situ hybridisation with their own cut-offs.
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