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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.
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.
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.
This was the first proof that a monoclonal antibody against a growth receptor could extend life in a common solid tumour, and it created HER2-positive breast cancer as a disease treated differently from the rest. Its cardiac finding shaped every later HER2 regimen, which pair trastuzumab with taxanes rather than anthracyclines.
This review is the conceptual basis for trastuzumab, pertuzumab, HER2 antibody-drug conjugates and EGFR inhibitors, and for the HER3-mediated resistance that later drugs try to overcome.
This study confirmed HER2 as a prognostic marker and a therapeutic target, showed that immunohistochemistry could identify the patients, and extended the target to ovarian cancer. It set up the clinical development of trastuzumab and the HER2 testing that every breast cancer now receives.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2, HER2-positive breast cancer.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2, HER2-positive breast cancer.
Shares Dennis J. Slamon, HER2, HER2-positive breast cancer.
Shares Slamon 1989: HER2/neu in human breast and ovarian cancer, Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2, Triple-negative breast cancer (TNBC).
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2-positive breast cancer.
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2, Triple-negative breast cancer (TNBC).
Shares Yarden and Sliwkowski 2001: untangling the ErbB signalling network, HER2.