Background
Methods
The PRAEGNANT research network
The SHERBOC trial
Computerized phenotyping of patients from the PRAEGNANT database
Patients
Data collection
Definition of hormone receptor, HER2 status, and grading
HRG testing
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Cancer cell content assessment, excluding any slides with < 50 cancer cells in total
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Scoring of cancer cells: 0, 0 RNA-ISH dots; 1, 1–3 dots per tumor cell; 2, > 4 dots per tumor cell
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Overall HRG expression was computed as the highest score in at least 10% of tumor cells
Statistical analysis
Results
Patient and disease characteristics
HRG expression
Characteristic | SHERBOC no(n = 525) | SHERBOC yes(n = 125) |
---|---|---|
Age at study entry (years) | 60.9 (13.1) | 61.1 (11.9) |
BMI (kg/m2) | 26.6 (5.9) | 26.0 (5.6) |
Time from diagnosis to metastasis (years) | 6.0 (6.5) | 6.9 (7.5) |
Tumor grade | ||
1 | 38 (7.8) | 13 (12.5) |
2 | 333 (68.4) | 75 (72.1) |
3 | 116 (23.8) | 16 (15.4) |
ECOG score | ||
0 | 251 (50.3) | 82 (67.8) |
1 | 192 (38.5) | 33 (27.3) |
≥ 2 | 56 (11.2) | 6 (5.0) |
Concomitant diseases | ||
0 or 1 | 242 (46.4) | 62 (50.4) |
2 to 4 | 192 (36.8) | 46 (37.4) |
≥ 5 | 88 (16.9) | 15 (12.2) |
Metastasis pattern | ||
Brain | 48 (9.2) | 4 (3.3) |
Visceral | 237 (45.3) | 42 (34.1) |
Bone | 88 (16.8) | 29 (23.6) |
Other | 150 (28.7) | 48 (39.0) |
HRG test | ||
Negative | – | 18 (47.4)a |
Positive | – | 14 (36.8)a |
Not evaluable | – | 6 (15.8)a |
Ever received chemotherapy | ||
No | 279 (53.1) | 125 (100.0) |
Yes | 246 (46.9) | 0 (0.0) |
Ever received endocrine therapy | ||
No | 109 (20.8) | 12 (9.6) |
Yes | 416 (79.2) | 113 (90.4) |
Ever received fulvestrant | ||
No | 356 (67.8) | 125 (100.0) |
Yes | 169 (32.2) | 0 (0.0) |
Previous CDK4/6i documented | ||
No | 405 (77.1) | 4 (3.2)b |
Yes | 120 (22.9) | 121 (96.8) |
SHERBOC line | ||
1 | 290 (55.2) | 117 (93.6) |
2 | 235 (44.8) | 8 (6.4) |
Characteristic | HRG-negative (n = 18) | HRG-positive (n = 14) |
---|---|---|
Age at study entry (years) | 61.6 (15.0) | 56.3 (10.1) |
BMI (kg/m2) | 25.6 (4.3) | 24.9 (4.2) |
Time from diagnosis to metastasis (years) | 5.6 (5.8) | 3.8 (4.4) |
Tumor grade | ||
1 | 2 (11.8) | 2 (18.2) |
2 | 11 (64.7) | 7 (63.6) |
3 | 4 (23.5) | 2 (18.2) |
ECOG score | ||
0 | 13 (76.5) | 11 (84.6) |
1 | 4 (23.5) | 2 (15.4) |
2+ | 0 (0.0) | 0 (0.0) |
Concomitant diseases | ||
0 or 1 | 8 (44.4) | 10 (76.9) |
2 to 4 | 10 (55.6) | 2 (15.4) |
5+ | 0 (0.0) | 1 (7.7) |
Metastasis pattern | ||
Brain | 0 (0.0) | 1 (7.1) |
Visceral | 4 (22.2) | 9 (64.3) |
Bone | 2 (11.1) | 1 (7.1) |
Other | 12 (66.7) | 3 (21.4) |
Ever received chemotherapy | ||
No | 18 (100.0) | 14 (100.0) |
Yes | 0 (0.0) | 0 (0.0) |
Ever received endocrine therapy | ||
No | 1 (5.6) | 1 (7.1) |
Yes | 17 (94.4) | 13 (92.9) |
Ever received fulvestrant | ||
No | 18 (100.0) | 14 (100.0) |
Yes | 0 (0.0) | 0 (0.0) |
Previous CDK4/6i documented | ||
No | 0 (0.0) | 1 (7.1)a |
Yes | 18 (100.0) | 13 (92.9) |
SHERBOC line | ||
1 | 17 (94.4) | 12 (85.7) |
2 | 1 (5.6) | 2 (14.3) |
Comparison of selected versus nonselected patients
Outcome | Unadjusted analysis | Adjusted analysis b | ||
---|---|---|---|---|
Hazard ratio (95% CI) | P value | Hazard ratio (95% CI) | P value | |
PFS-1TLc | 0.44 (0.27, 0.72) | < 0.01 | 0.60 (0.36, 0.98) | 0.04 |
OS-1TLc | 0.10 (0.02, 0.40) | < 0.01 | 0.14 (0.03, 0.59) | < 0.01 |
Progression-free survival | Overall survival | |||
---|---|---|---|---|
SHERBOC no | SHERBOC yes | SHERBOC no | SHERBOC yes | |
At risk | 306 | 74 | 306 | 74 |
Events | 169 | 18 | 87 | 2 |
Median survival time (months) | 11.3 (8.9, 16.1) | – | – | – |
6-month survival rate | 0.66 (0.61, 0.72) | 0.83 (0.74, 0.92) | 0.84 (0.80, 0.88) | 1.00 (1.00, 1.00) |
1-year survival rate | 0.48 (0.42, 0.55) | 0.76 (0.65, 0.88) | 0.72 (0.66, 0.77) | 0.96 (0.90, 1.00) |
2-year survival rate | 0.34 (0.28, 0.41) | 0.63 (0.49, 0.82) | 0.62 (0.55, 0.69) | 0.96 (0.90, 1.00) |