Background
Methods
Patients and treatments
Statistical analysis
Results
Patient characteristics and treatments
Patient and tumor characteristics | HER-2 negative patients | HER-2 positive patients not treated with trastuzumab | HER-2 positive patients treated with trastuzumab | Whole population | P value |
---|---|---|---|---|---|
N = 78 | N = 20 | N = 32 | N = 130 | ||
-60% | -15.38% | -24.62% | |||
Age at BM diagnosis (years)- median (range) | |||||
< 65 years | 54(34-83) | 53 (33- 75) | 47(26-67) | 52(26-83) | 0.0178 |
≥ 65 years | 59/77 (76.62) | 15/20 (75) | 31/32 (96.88) | 105/129 (81.4) | |
18/77 (23.38) | 5/20 (25) | 1/32 (3.12) | 24/129 (18.6) | ||
Karnofsky performance status | |||||
< 70 | 32/76 (42.11) | 10/20 (50) | 6/31 (19.35) | 48/127 (37.8) | 0.0418 |
≥ 70 | 44/76 (57.89) | 10/20 (50) | 25/31 (80.65) | 79/127 (62.2) | |
RTOG RPA class | 0 | 0 | 0 | 0 | 0.0391 |
I | 43/75 (57.33) | 10/20 (50) | 25/31 (80.65) | 78/126 (61.9) | |
II | 32/75 (42.67) | 10/20 (50) | 6/31 (19.35) | 48/126 (38.1) | |
III | |||||
Histology of primary BC | |||||
Ductal | 70/76 (92.11) | 19/20 (95) | 30/32 (93.75) | 119/128 (92.97) | 0.5172** (ns) |
Lobular | 2/76 (2.63) | 0 | 2/32 (6.25) | 4/128 (3.12) | |
Other | 4/76 (5.26) | 1/20 (5) | 0 | 5/128 (3.91) | |
Histologic grade | |||||
SBR I | 2/70 (2.86) | 1/17 (5.88) | 1/31 (3.23) | 4/118 (3.39) | 0.063** (ns) |
SBR II | 27/70 (38.57) | 1/17 (5.88) | 11/31 (35.48) | 39/118 (33.05) | |
SBRIII | 41/70 (58.57) | 15/17 (88.24) | 19/31 (61.29) | 75/118 (63.56) | |
Tumor HR status | |||||
Positive | 48/76 (63.16) | 9/19 (47.37) | 17/32 (53.12) | 72/127 (56.69) | 0.1996 (ns) |
Negative | 28/76 (36.84) | 10/19 (52.63) | 15/32 (46.88) | 55/127 (43.31) | |
Number of BM | |||||
Single | 6/78 (7.69) | 0 | 0 | 6/130 (4.62) | 0.1339** (ns) |
Multiple | 72/78 (92.31) | 20/20 (100) | 32/32 (100) | 124/130 (95.38) | 0.1778 **(ns) |
Meningitis | 17/77 (22.08) | 1/20 (5) | 4/31 (12.9) | 22/128 (17.19) | |
Yes | 60/77 (77.92) | 19/20 (95) | 27/31 (87.1) | 106/128 (82.81) | |
No | |||||
Number of other metastatic sites | |||||
0 (BM alone) | 6/78 (7.69) | 1/20 (5) | 0 | 7/130 (5.38) | 0.2971** (ns) |
1 | 19/78 (24.36) | 3/20 (15) | 9/32 (28.12) | 31/130 (23.85) | |
2 | 20/78 (25.64) | 7/20 (35) | 14/32 (43.75) | 41/130 (31.54) | |
> 2 | 33/78 (42.31) | 9/20 (45) | 9/32 (28.12) | 51/130 (39.23) | |
Concomitant and other metastases | |||||
Liver | 35/78 (44.87) | 12/20 (60) | 23/32 (71.88) | 70/130 (53.85) | 0.0299 |
Lung | 36/78 (46.15) | 11/20 (55) | 14/32 (43.75) | 61/130 (46.92) | 0.7147 (ns) |
Bone | 51/78 (65.38) | 10/20 (50) | 18/32 (56.25) | 79/130 (60.77) | 0.3783 (ns) |
Previous chemotherapy | 55/78 (70.51) | 18/20 (90) | 32/32 (100) | 105/130 (80.77) | 0.0002** |
Yes | 23/78 (29.49) | 2/20 (10) | 0 | 25/130 (19.23) | |
No | |||||
Previous taxane-based chemotherapy | 36/78 (46.15) | 11/20 (55) | 25/31 (80.65) | 72/129 (55.81) | 0.0047 |
Yes | 42/78 (53.85) | 9/20 (45) | 6/31 (19.35) | 57/129 (44.19) | |
No | |||||
Lactate Deshydrogenase (LDH) | 35/61 (57.38) | 9/14 (64.29) | 13/19 (68.42) | 57/94 (60.64) | 0.6597 (ns) |
≤ 500 UI/L | 26/61 (42.62) | 5/14 (35.71) | 6/19 (31.58) | 37/94 (39.36) | |
500 UI/L | 127-2088 | 120-3469 | 158-2199 | 120-3469 | |
range | |||||
Lymphocyte count | 25/70 (35.71) | 9/20 (45) | 3/20 (15) | 37/110 (33.64) | 0.1106 (ns) |
≤ 0.7 G/L | 45/70 (64.29) | 11/20 (55) | 17/20 (85) | 73/110 (66.36) | |
> 0.7 G/L | 61-2285 | 40-1814 | 63-2050 | 40-2285 | |
range | |||||
Vital Status | 16/78 (20.51) | 2/20 (10) | 14/32 (43.75) 18/32 (56.25) | 32/130 (24.62) | 0.0138** |
alive | 62/78 (79.49) | 18/20 (90) | 98/130 (75.38) | ||
dead |
Patient outcomes
n | Median Survival (months) | 6 months [CI95%] | 1 year [CI95%] | P value | |
---|---|---|---|---|---|
Whole population | 130 | 7.43 (5.52 -9.73) | 54.9 [46.8; 64.3] | 35.8 [28; 45.7] | |
RTOG RPA | 44.6 [34.3; 58.1] | 0.001 | |||
Class I-II | 78 | 9.63 (7.69-15.72) | 65.9 [56; 77.5] | 23.9 [14.2; 40.4] | |
Class III | 48 | 3.52 (2.86-7.36) | 37.7 [26; 54.7] | ||
0.004 | |||||
HER-2 negative patients | 78 | 5.88 [3.75; 9.63] | 48.7 [37.7; 63] | 26.1 [16.8; 40.7] | |
HER-2 positive patients not treated with trastuzumab | 20 | 5.65 [2.60; 12.49] | 45.5 [31.3; 66.1] | 29.2 [17-50.2] | |
HER-2 positive patients treated with trastuzumab | 32 | 19.53 [9.27; NA] | 77.1 [63.5; 93.6] | 62.6 [47.2; 83] | |
Trastuzumab | 10 | 9.17 (5.52-NA) | 63.6 [40.7; 99.5] | 43.6 [21.8; 87.4] | 0.113 |
Stopped | 22 | 20.91 (19.53-NA) | 94.4 [84.4; 100] | 88.5 [74.8; 100] | |
Continued |
Covariate | Comparison | Hazard Ratio [CI 95%] | P N = 130 |
---|---|---|---|
Age at BM diagnosis | ≥ 50 Vs. < 50 | 1.21 [0.80; 1.81] | 0.329 |
KPS | ≥ 70 vs. < 70 | 0.51 [0.34; 0.77] | 0.0013 |
RTOG RPA class | III vs. I-II | 1.98 [1.32; 2.98] | 0.0013 |
Time interval (y) between primary tumor and BM diagnosis | ≥ 2 vs. < 2 | 3.76 [0.52; 27.18] | 0.968 |
Brain metastases | Presence of systemic metastases vs. Alone | 1.52 [0.62; 3.74] | 0.366 |
Visceral metastases | Yes vs No | 1.34 [0.84; 2.11] | 0.2159 |
Bone metastases | Yes vs No | 1.07 [0.71; 1.60] | 0.745 |
No. of BM | Multiple vs. single | 1.12 [0.41; 3.06] | 0.822 |
Nb of other metastatic sites | Multiple vs. single | 1.516 [0.6148; 3.74] | 0.3627 |
Histology | lobular and other vs. ductal | 0.77 [0.34; 1.77] | 0.545 |
Tumor HR status | Negative vs. positive | 1.37 [0.91; 2.06] | 0.127 |
HER-2 overexpression | Negative vs. positive | 1.48 [0.98; 2.24] | 0.0606 |
Trastuzumab-based therapy for HER2 overexpressing tumor | Yes vs No | 0.45 [0.27; 0.75] | 0.001631 |
HR- & HER2- | Yes vs No | 2.17 [1.38; 3.43] | 0.0006 |
SBR grade | 3 vs. 1-2 | 1.59 [1.00; 2.52] | 0.0484 |
LDH (U/L) | > 500 vs. ≤ 500 | 2.01 [1.27; 3.16] | 0.0026 |
Lymphocyte count | > 700 vs. ≤ 700 | 0.58 [0.37; 0.89] | 0.0138 |
Total radiation dose (Gy) | > 30 vs. ≤ 30 | 1.54 [0.49; 4.91] | 0.463 |
Covariate | Comparison | Hazard Ratio for death [CI 95%] | P N = 127 |
---|---|---|---|
HER-2 positive patients treated with trastuzumab | Yes vs No | 0.49 [0.29;0.83] | 0.00810 |
KPS | ≥ 70 vs. < 70 | 0.56 [0.37; 0.85] | 0.00578 |