HER2 gene copy number and breast cancer-specific survival.
OBJECTIVE
HER2 amplification occurs in 10-15% of breast cancers. It is associated with poor breast cancer-specific survival (BCSS) and is an important prognostic and predictive marker. While it has been accepted that the HER2:chromosome 17 centromere (CEP17) ratio determines HER2 status, recent guidelines acknowledge the significance of HER2 copy number alone. The aims of this study were to assess BCSS according to mean HER2 copy number and HER2 status expressed as a HER2:CEP17 ratio with and without increased CEP17 copy number.


RESULTS
The study population comprised breast cancer patients treated with surgery only and with long-term follow-up. In situ hybridization for HER2:CEP17 was performed on tissue microarrays and was successful in 679 cases. These were included in the study. Kaplan-Meier methods were used to estimate BCSS. A total of 47 cases had ≥4 < 6 HER2 copies; 16 were HER2+and 31 were HER2-by ratio. Eighty-five cases had ≥6 copies of HER2 and only two of these were HER2-by ratio. The risk of death from breast cancer was increased among those with ≥6 HER2 compared to cases with 0-3.9 HER2 signals [hazard ratio (HR): 2.05; confidence interval (CI): 1.49-2.82 (unadjusted)]. After adjusting for stage, there was increased risk of death from breast cancer during the first 5 years after diagnosis in cases that were HER2-by ratio but with ≥4 < 6 HER2 (HR: 2.38; CI: 1.23-4.60).


CONCLUSIONS
Increased copy number of HER2 may confer an increased risk of death from breast cancer despite negative HER2 status by ratio.
School of Medicine, University of Bologna, Alma Mater Studiorum, Bologna, Italy.
Giovanni B
GB
Biserni
Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Breast and Endocrine Surgery, St Olav's Hospital, Trondheim, Norway.
Monica J
MJ
Engstrøm
Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway. anna.bofin@ntnu.no.
Anna M
AM
Bofin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage / Q000235:genetics; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis
HER2 copy number; breast cancer-specific survival; in situ hybridization