Table 2.
Association of ESR1 fusions with clinical parameters in the predictive cohort
| Predictive Endocrine Therapy Cohorts | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parameters | n |
at least one ESR1-CCDC170 (exon 2 to 8) fusion |
P-Value | ESR1-CCDC170 (exon 2) fusion | PValue | ESR1-CCDC170 (exon 8) fusion | P-Value | ESR1-AKAP12 | P-Value | ||||
| n | % | n | % | n | % | n | % | ||||||
| All patients | 322 | 89 | 27.6% | 50 | 15.5% | 51 | 15.8% | 13 | 4.0% | ||||
| Age at start 1st line treatment (years) | |||||||||||||
| ≤ 50 | 63 | 19 | 30.2% | 0.63 | 12 | 19.0% | 0.62 | 8 | 12.7% | 0.029 | 1 | 1.6% | 0.36 |
| > 50- ≤ 70 | 161 | 37 | 23.0% | 23 | 14.3% | 24 | 14.9% | 7 | 4.3% | ||||
| > 70 | 98 | 33 | 33.7% | 15 | 15.3% | 19 | 19.4% | 5 | 5.1% | ||||
| Menopausal status at start of 1st line treatment | |||||||||||||
| Premenopausal | 64 | 17 | 26.6% | 0.82 | 10 | 15.6% | 0.99 | 8 | 12.5% | 0.41 | 1 | 1.6% | 0.26 |
| Postmenopausal | 257 | 72 | 28.0% | 40 | 15.6% | 43 | 16.7% | 12 | 4.7% | ||||
| Surgery type | |||||||||||||
| Lumpectomy | 95 | 25 | 26.3% | 0.79 | 14 | 14.7% | 0.90 | 15 | 15.8% | 0.83 | 2 | 2.1% | 0.89 |
| Ablation | 169 | 42 | 24.9% | 24 | 14.2% | 25 | 14.8% | 4 | 2.4% | ||||
| Radiotherapy | |||||||||||||
| No | 105 | 30 | 28.6% | 0.33 | 20 | 19.0% | 0.08 | 16 | 15.2% | 0.98 | 2 | 1.9% | 0.74 |
| Yes | 159 | 37 | 23.3% | 18 | 11.3% | 24 | 15.1% | 4 | 2.5% | ||||
| Nodal status | |||||||||||||
| No lymph nodes | 122 | 33 | 27.0% | 0.88 | 19 | 15.6% | 0.99 | 20 | 16.4% | 0.95 | 4 | 3.3% | 0.2 |
| Positive lymph nodes | 130 | 38 | 29.2% | 21 | 16.2% | 22 | 16.9% | 9 | 6.9% | ||||
| Tumor outside lymph nodes | 53 | 15 | 28.3% | 8 | 15.1% | 7 | 13.2% | 0 | 0.0% | ||||
| Not applicable (M1) | 16 | 3 | 18.8% | 2 | 12.5% | 2 | 12.5% | 0 | 0.0% | ||||
| Pathological Tumor classification | |||||||||||||
| pT1 | 85 | 22 | 25.9% | 0.60 | 13 | 15.3% | 0.21 | 14 | 16.5% | 0.90 | 2 | 2.4% | 0.36 |
| pT2 + unknown | 186 | 50 | 26.9% | 25 | 13.4% | 30 | 16.1% | 10 | 5.4% | ||||
| pT3 + pT4 | 51 | 17 | 33.3% | 12 | 23.5% | 7 | 13.7% | 1 | 2.0% | ||||
| Tumor grade | |||||||||||||
| Poor | 160 | 45 | 28.1% | 0.36 | 27 | 16.9% | 0.60 | 27 | 16.9% | 0.60 | 7 | 4.4% | 0.078 |
| Unknown | 81 | 18 | 22.2% | 10 | 12.3% | 10 | 12.3% | 0 | 0.0% | ||||
| Moderate/Good | 74 | 24 | 32.4% | 13 | 17.6% | 13 | 17.6% | 5 | 6.8% | ||||
| Tumor cell content | |||||||||||||
| 30–49% | 27 | 7 | 25.9% | 0.96 | 4 | 14.8% | 0.99 | 2 | 7.4% | 0.25 | 2 | 7.4% | 0.63 |
| 50–70% | 98 | 28 | 28.6% | 15 | 15.3% | 13 | 13.3% | 4 | 4.1% | ||||
| > 70% | 197 | 54 | 27.4% | 31 | 15.7% | 36 | 18.3% | 7 | 3.6% | ||||
| Hormone/ growth factor status (RT-qPCR) | |||||||||||||
| ESR1-negative | 0 | 0 | 0 | 0 | 0 | ||||||||
| ESR1-positive | 322 | 89 | 27.6% | 50 | 15.5% | 51 | 15.8% | 13 | 4.0% | ||||
| PR-negative | 63 | 18 | 28.6% | 0.87 | 11 | 17.5% | 0.65 | 11 | 17.5% | 0.70 | 6 | 9.5% | 0.014 |
| PR-positive | 258 | 71 | 27.5% | 39 | 15.1% | 40 | 15.5% | 7 | 2.7% | ||||
| HER2 non-amplified | 279 | 77 | 27.6% | 0.63 | 44 | 15.8% | 0.85 | 45 | 16.1% | 0.81 | 13 | 4.7% | 0.16 |
| HER2 amplified | 41 | 12 | 29.3% | 6 | 14.6% | 6 | 14.6% | 0 | 0.0% | ||||
| CCDC170 negative | 31 | 5 | 16.1% | 0.13 | 2 | 6.5% | 0.15 | 4 | 12.9% | 0.62 | 0 | 0.0% | 0.23 |
| CCDC170 positive | 287 | 83 | 28.9% | 47 | 16.4% | 47 | 16.4% | 13 | 4.5% | ||||
| Adjuvant endocrine therapy | |||||||||||||
| No | 252 | 66 | 26.2% | 0.24 | 38 | 15.1% | 0.64 | 36 | 14.3% | 0.13 | 7 | 2.8% | 0.030 |
| Yes (AI cohort only) | 69 | 23 | 33.3% | 12 | 17.4% | 15 | 21.7% | 6 | 8.7% | ||||
| Adjuvant chemotherapy | |||||||||||||
| No | 267 | 76 | 28.5% | 0.47 | 40 | 15.0% | 0.55 | 45 | 16.9% | 0.27 | 12 | 4.5% | 0.36 |
| Yes | 55 | 13 | 23.6% | 10 | 18.2% | 6 | 10.9% | 1 | 1.8% | ||||
| Disease-free interval | |||||||||||||
| ≤ 1 year disease-free | 72 | 23 | 31.9% | 0.47 | 14 | 19.4% | 0.62 | 12 | 16.7% | 0.99 | 2 | 2.8% | 0.45 |
| 1–3 years disease-free | 137 | 37 | 27.0% | 20 | 14.6% | 20 | 14.6% | 8 | 5.8% | ||||
| > 3 years disease-free | 113 | 29 | 25.7% | 16 | 14.2% | 19 | 16.8% | 3 | 2.7% | ||||
| Dominant site of metastasis | |||||||||||||
| Local regional | 29 | 10 | 34.5% | 0.51 | 7 | 24.1% | 0.32 | 4 | 13.8% | 0.36 | 0 | 0.0% | 0.40 |
| Bone | 159 | 40 | 25.2% | 25 | 15.7% | 21 | 13.2% | 6 | 3.8% | ||||
| Other distant metastasis | 130 | 38 | 29.2% | 17 | 13.1% | 25 | 19.2% | 7 | 5.4% | ||||
| Response type | |||||||||||||
| Complete response | 11 | 3 | 27.3% | 0.87 | 2 | 18.2% | 0.73 | 1 | 9.1% | 0.29 | 0 | 0.0% | 0.46 |
| Partial response | 39 | 9 | 23.1% | 3 | 7.7% | 6 | 15.4% | 2 | 5.1% | ||||
| Stable disease over 6 months (SD > 6 m) | 115 | 32 | 27.8% | 16 | 13.9% | 23 | 20.0% | 1 | 0.9% | ||||
| Stable disease for 6 months or less (SD ≤ 6 m) | 13 | 2 | 15.4% | 2 | 15.4% | 1 | 7.7% | 0 | 0.0% | ||||
| Progressive disease (PD) | 83 | 20 | 24.1% | 14 | 16.9% | 8 | 9.6% | 3 | 3.6% | ||||
| Response type | |||||||||||||
| No response | 96 | 22 | 22.9% | 0.50 | 16 | 16.7% | 0.38 | 9 | 9.4% | 0.05 | 3 | 3.1% | 0.50 |
| Response | 165 | 44 | 26.7% | 21 | 12.7% | 30 | 18.2% | 3 | 1.8% | ||||
ESR1 estrogen receptor alpha, CCDC170 coiled-coil domain containing 170, AKAP12 A-Kinase Anchoring Protein 12 gene, ESR1-CCDC170 ESR1-CCDC170 gene fusion, ESR1-AKAP12 ESR1-AKAP12 gene fusion, M1 methastatic stage 1, pT primary tumor, pT1 small primary tumor (tumour is 2 cm across or less), pT2 tumour more than 2 cm but no more than 5 cm across, pT3 T3 tumour bigger than 5 cm across, pT4 tumor with phatological stage, RT-qPCR Quantitative Real-Time Polymerase Chain Reaction, PR progesterone receptor, HER2 human epidermal growth factor receptor, AI aromatase inhibitors, SD standard deviation, PD progressive disease
Statistically significant differences are indicated in bold