Introduction
Materials and methods
Patients and tumor material
HER2+ | HER2-* | |
---|---|---|
Number of tumors | 200 | 554 |
Number of primary tumors | 176 | -- |
Number of metastases | 5 | -- |
Unknown status | 19 | -- |
Tumor size
| ||
≤20 mm | 57 | 205 |
>20 mm | 134 | 226 |
Mean size mm (SD) | 29 (16) | 26 (14) |
Histological grade
| ||
Grade 1 | 1 | 41 |
Grade 2 | 26 | 134 |
Grade 3 | 38 | 134 |
Estrogen receptor status
| ||
Positive | 76 | 306 |
Negative | 122 | 149 |
Lymph node status
| ||
Negative | 69 | 244 |
Positive | 123 | 194 |
Age
| ||
Median age in years (range) | 56 (27 to 84) | 55 (28 to 94) |
<50 years | 77 | 212 |
≥50 years | 109 | 252 |
DNA ploidy status
| ||
Aneuploid | 112 | -- |
Diploid | 39 | -- |
Unknown | 49 | -- |
Gene expression subtype**
| ||
Basal-like | 7 | 135 |
ERBB2 | 51 | 6 |
Normal-like | 9 | 35 |
Luminal A | 4 | 153 |
Luminal B | 10 | 77 |
Unclassified | 6 | 42 |
Overall survival***
| ||
Number of deaths | 109 | 190 |
Within five years | 80 | 107 |
Median survival in years (range) | 7 (0.16 to 18.5) | 7.6 (0.1 to 31.9) |
Median follow-up in years for patients still alive (range) | 12.8 (7 to 18.5) | 10.2 (1.5 to 20.2) |
aCGH analysis
Zoom-in aCGH analysis
Identification of significant copy number alterations and fraction of the genome altered
External aCGH data sets for comparison
Gene expression analysis
Correlation of gene expression data with genomic aberrations
Survival analysis
Results
Extent and patterns of 17q12-q21 amplification in HER2+ breast cancer
Extent and patterns of significant CNAs on chromosome 17 in HER2+ breast cancer
Recurrent amplifications and firestorm-like amplification patterns in HER2+ breast cancer
Comparison of DNA copy number alterations in HER2+ and HER2- breast cancer
Differences between HER2+ and basal-like breast cancer
DNA copy number alterations in subgroups of HER2+ breast cancer
Associations of histopathological and genomic characteristics with overall survival
Investigated covariatea | Number tumors | Log-rank
P
| Univariate
P
| Multivariate
P
b
|
---|---|---|---|---|
ER+ vs. ER- | 64/112 | 0.96 | 0.96 | 0.79 |
LN+ vs. LN- | 110/65 | 4 × 10-6 *** | 9 × 10-6 *** | 0.0002*** |
Size >20 mm vs. ≤ 20 mm | 122/49 | 0.002** | 0.002** | 0.02* |
Histological grade 3 vs. 1 and 2 | 37/26 | 0.91 | 0.91 | 0.83 |
Age <50 vs. ≥50 years | 73/103 | 0.22 | 0.23 | 0.77 |
DNA Aneuploid vs. Diploid | 106/37 | 0.001** | 0.001** | 0.005** |
DNA Aneuploid vs. Diploid ER+ | 37/11 | 0.008** | 0.02* | 0.07 |
DNA Aneuploid vs. Diploid ER- | 69/26 | 0.05* | 0.05* | 0.06 |
Recurrent 17q amplification, yes vs. no | 70/106 | 0.17 | 0.17 | 0.13 |
Recurrent amplification excluding 17q, yes vs. no | 76/100 | 0.75 | 0.75 | 0.7 |
Firestorm pattern, yes vs. no | 78/98 | 0.27 | 0.28 | 0.58 |
High FGA vs. low FGAc | 42/46 | 0.08 | 0.09 | 0.25 |
High FGA vs. low FGA ER+ tumorsc | 18/17 | 0.09 | 0.09 | 0.26 |
High FGA vs. low FGA ER- tumorsc | 24/29 | 0.37 | 0.37 | 0.55 |