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HER2+ Disease
HER2+ status associated with more aggressive disease and poorer outcomes
HER2+ breast cancer is an especially aggressive form of the disease 1-3
- HER2 overexpression has been associated with increased metastasis and angiogenesis 4
- Patients with HER2+ disease experience increased risk of disease recurrence and inferior survival 1, 5
Increases risk in node-negative tumors
In a retrospective study of node-negative invasive breast cancer, HER2 gene amplification strongly impacted the risk for both early recurrence and disease-related death 6
*Based on a sample of 324 node-negative archival breast cancer specimens. Patients were treated by surgery only. Early recurrent disease (n=242 cases) was defined as occurring within 24 months of diagnosis. Evaluation of disease-related death was restricted to 232 patients known to have died of disease, or who had at least 36 months of follow-up.
†Small tumors defined as ≤ 1.0 cm in diameter; large tumors defined as >1.0 cm in diameter.
- HER2 gene amplification is the underlying biologic change that results in continuous HER2 overexpression 7
- HER2 overexpression continues throughout the course of the disease and drives tumor growth 7-9
Increases risk in hormone-receptor-positive (HR+) tumors 10
- HER2 overexpression predicts poor results even in patients whose breast cancers overexpress hormone-receptors (HR+ tumors)
- Based on a 2005 clinical study by Gago et al, HER2+ tumors are associated with significantly worse disease-free survival (DFS) (P<0.001) and overall survival (OS) (P=0.001) than HER2-negative tumors
Study design: This prospective clinical trial included 516 consecutive patients with previously untreated stage I or stage II primary breast cancer, 180 of whom had HR+ tumors. All patients received tamoxifen alone or chemotherapy plus tamoxifen. Patients were followed for 5 to 10 years (mean of 7.3). Immunohistochemistry of tumor biopsies was used to determine protein expression.
- References:
- 1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neuoncogene. Science. 1987; 235:177-182.
- 2. Paik S, Hazan R, Fisher ER, et al. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. JClin Oncol.1990;8:103-112.
- 3. Ross JS, Fletcher JA.HER-2/neu (c-erb-B2) gene and protein in breast cancer. AmJClin Pathol.1999;112(suppl 1):S53-S67.
- 4. Niu G, Carter WB. Human epidermal growth factor receptor 2 regulates angiopoietin-2 expression in breast cancer via AKT and mitogen-activated protein kinase pathways. Cancer Res. 2007; 67:1487-1493.
- 5. Witton CJ, Reeves JR, Going JJ, et al. Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. JPathol. 2003; 200: 290-297.
- 6. Press MF, Bernstein L, Thomas PA, et al.HER-2/neu gene amplification characterized by fluorescence in situhybridization: poor prognosis in node-negative breast carcinomas. JClin Oncol.1997;15: 2894-2904.
- 7. Pegram M, Slamon D. Biological rationale for HER2/neu (c-erbB2) as a target for monoclonal antibody therapy. Semin Oncol.2000;27(suppl 9):13-19.
- 8. Simon R, Nocito A, Hubscher T, et al. Patterns of Her-2/neu amplification and overexpression in primary and metastatic breast cancer. JNatl Cancer Inst. 2001;93:1141-1146.
- 9. Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999; 26(suppl 12):60-70.
- 10. Gago EE, Fanelli MA, Ciocca DR. Co-expression of steroid hormone-receptors (estrogen receptor alpha and/or progesterone receptors) and Her2/neu (c-erbB-2) in breast cancer: clinical outcome following tamoxifen-based adjuvant therapy. JSteroid Biochem Mol Biol.2006; 98:36-40.
