Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/neuOncogene¶
Why this mattered¶
Slamon and colleagues helped turn breast cancer from a disease classified mainly by anatomy and histology into one that could be stratified by a specific molecular alteration with clinical consequences. The key shift was not simply that HER-2/neu was amplified in some tumors, but that amplification in primary breast cancers correlated strongly with relapse and survival, especially in lymph node-positive disease, and remained significant after comparison with established prognostic factors. This made an oncogene alteration clinically legible: a DNA-level change could mark a biologically distinct and more aggressive form of breast cancer.
The paper also made possible a new kind of translational path. If HER2 amplification was associated with tumor behavior, then HER2 was not only a prognostic marker but a plausible therapeutic target and a basis for patient selection. That logic became central to later HER2 testing, molecular subtyping of breast cancer, and the development of HER2-directed therapy, most notably trastuzumab. The eventual success of anti-HER2 treatment depended on the paradigm this study crystallized: cancer patients could be identified by the molecular drivers of their tumors, and therapies could be designed and evaluated in those biologically defined groups.
In retrospect, the 1987 study sits at the beginning of precision oncology in solid tumors. It connected oncogene biology, clinical prognosis, diagnostic testing, and targeted drug development in a single disease context. Later breakthroughs in breast cancer genomics and targeted therapy extended this framework, but the central claim had already been made here with unusual clarity: molecular alterations in tumors were not merely laboratory observations; they could explain clinical outcomes and reshape how cancer was classified, studied, and treated.
Abstract¶
The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene has been shown to be amplified in human breast cancer cell lines. In the current study, alterations of the gene in 189 primary human breast cancers were investigated. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors. Correlation of gene amplification with several disease parameters was evaluated. Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer. It retained its significance even when adjustments were made for other known prognostic factors. Moreover, HER-2/neu amplification had greater prognostic value than most currently used prognostic factors, including hormonal-receptor status, in lymph node-positive disease. These data indicate that this gene may play a role in the biologic behavior and/or pathogenesis of human breast cancer.
Related¶
- cite → Regression Models and Life-Tables — The HER-2/neu breast-cancer study uses Cox regression to relate oncogene amplification to relapse and survival risk.
- cite → Nonparametric Estimation from Incomplete Observations — The HER-2/neu breast-cancer study uses Kaplan-Meier survival estimation to analyze censored relapse and survival data.
- enables → Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2 — The HER2/neu amplification-survival correlation identified HER2 overexpression as a therapeutic target for trastuzumab plus chemotherapy.
- enables → Comprehensive molecular portraits of human breast tumours — HER2/neu amplification as a prognostic breast cancer driver became one of the genomic alterations systematically characterized in TCGA's molecular portraits.
- cite ← Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2 — Trastuzumab plus chemotherapy targets the HER2 amplification and overexpression whose association with breast-cancer relapse and survival was established in the 1987 HER-2/neu study.
- cite ← Comprehensive molecular portraits of human breast tumours — The TCGA breast cancer study cites HER2/neu amplification as the foundational molecular alteration linking ERBB2 copy-number gain to breast cancer relapse and survival.
- enables ← Regression Models and Life-Tables — Cox proportional hazards regression enabled Slamon et al. to quantify the association between HER-2/neu amplification and breast-cancer relapse and survival.
- enables ← Nonparametric Estimation from Incomplete Observations — Kaplan-Meier estimation enabled Slamon et al. to compare censored relapse-free and overall survival curves by HER-2/neu amplification status.