Table 1 Clinical and pathological factors and treatment characteristics prior to CNS metastasis diagnosis according to BRCA mutation status- carriers (BRCA 1/2 Mt) vs non-carriers (BRCA non-Mt)
Characteristics | BRCA non-Mt (n = 50) | BRCA 1/2 Mt (n = 25) | Total (n = 75) | P-value | |
|---|---|---|---|---|---|
Tumor receptor status | BRCA1 (n = 19) | BRCA2 (n = 6) | – | ||
ER pos HER2 pos | 10 (20%) | 2 (10.5%) | 3 (50%) | 15 (11.25%) | |
ER pos HER2 neg | 20 (40%) | 7 (36%) | – | 27 (20.25%) | |
ER neg HER2 pos | 4 (8%) | 2 (10.5%) | – | 6 (4.5%) | |
Triple-negative | 16 (32%) | 8 (42%) | 3 (50%) | 27 (20.25%) | |
Age at breast cancer diagnosis (yr) | |||||
Median | 50 | 38.35 | 45.47 | < 0.0001 | |
Mean ± SD | 49.04 ± 9.37 | 39.44 ± 10.25 | 45.84 | ||
Range | 25.68–66.64 | 37.13–58.68 | 25.67–66.63 | ||
ECOG PS at breast cancer diagnosisa | |||||
ECOS PS 0 | 35 (70%) | 21 (84%) | 56 (74.7%) | 0.406 | |
ECOG PS 1 | 10 (20%) | 3 (12%) | 13 (17.3%) | ||
ECOG PS 2 | 5 (10%) | 1 (4%) | 6 (8%) | ||
ECOG PS 3 | 0 | 0 | 0 | ||
ECOG PS 4 | 0 | 0 | 0 | ||
Histology | |||||
IDC | 44 (88%) | 24 (96%) | 68 (90.7%) | 0.262 | |
ILC | 6 (12%) | 1 (4%) | 7 (9.3%) | ||
Tumor grade | |||||
Low (Grade 1) | 0 | 0 | 0 | 0.060 | |
Intermediate (Grade 2) | 16 (32%) | 3 (12%) | 19 (25.3%) | ||
High (Grade 3) | 34 (68%) | 22 (88%) | 56 (74.7%) | ||
Initial local treatment for breast cancerb | |||||
Lumpectomy+radiation | 22 (44%) | 13 (52%) | 35 (46.7%) | 0.611 | |
Mastectomy | 15 (30%) | 8 (32%) | 23 (30.7%) | ||
No treatment | 13 (26%) | 4 (16%) | 17 (22.7%) | ||
Axillary surgery | |||||
SLNBx | 30 (60%) | 16 (64%) | 46 (61.3%) | 0.330 | |
ALND | 7 (14%) | 5 (20%) | 12 (16%) | ||
None | 13 (26%) | 4 (16%) | 17 (22.7%) | ||
Risk-reducing mastectomy | |||||
Yes | 2 (4%) | 3 (12%) | 5 (6.7%) | 0.190 | |
No | 48 (96%) | 22 (88%) | 70 (93.3%) | ||
Gonadal ablation | |||||
Prophylactic BSO | 6 (12%) | 9 (36%) | 15 (20%) | 0.027 | |
Therapeutic BSO | 5 (10%) | 5 (20%) | 10 (13.3%) | ||
Ablative gonadal RT | 1 (2%) | 0 | 1 (1.3%) | ||
None | 38 (76%) | 11 (44%) | 49 (65.3%) | ||
Pathological tumor stage (size) (pT)c | |||||
T1 | 24 (48%) | 13 (52%) | 37 (49.3%) | 0.515 | |
T2 | 12 (24%) | 6 (24%) | 18 (24%) | ||
T3–4 | 1 (2%) | 2 (8%) | 3 (4%) | ||
NA/unknown | 13 (26%) | 4 (16%) | 17 (22.7%) | ||
Pathological nodal status (pN)c | |||||
N0 | 19 (38%) | 10 (40%) | 29 (38.7%) | 0.519 | |
N1 | 9 (18%) | 7 (28%) | 16 (21.3%) | ||
N2 | 6 (12%) | 4 (16%) | 10 (13.3%) | ||
N3 | 3 (6%) | 0 | 3 (4%) | ||
NA/unknown | 13 (26%) | 4 (16%) | 17 (22.7%) | ||
Disease spread at diagnosis | |||||
Local disease | 37 (74%) | 21 (84%) | 58 (77.3%) | 0.330 | |
Metastatic disease | 13 (26%) | 4 (16%) | 17 (22.7%) | ||
Chemotherapy-local disease (Neo-adj/ Adj) | |||||
Anthracycline based | 1 (2%) | 0 | 1 (1.3%) | 0.285 | |
Anthracycline+ | 18 (36%) | 15 (60%) | 33 (44%) | ||
Taxane based | |||||
Taxane-based | 9 (18%) | 2 (8%) | 11 (14.7%) | ||
Non Taxane-non | 10 (20%) | 5 (20%) | 15 (20%) | ||
Anthracyclined | |||||
None | 12 (24%) | 3 (12%) | 15 (20%( | ||
Hormonal therapy- local disease (Neo-adj/ Adj) | |||||
Tamoxifen | 11 (22%) | 6 (24%) | 17 (22.7%) | 0.523 | |
AI | 3 (6%) | 4 (16%) | 7 (9.3%) | ||
Tamoxifen followed by AI | 6 (12%) | 3 (12%) | 9 (12%) | ||
None | 30 (60%) | 12 (48%) | 42 (56%) | ||
anti-HER2- local disease (Neo-adj/ Adj) | |||||
Trastuzumab | 4 (8%) | 2 (8%) | 6 (8%) | 0.598 | |
Trastuzumab+Pertuzumab | 2 (4%) | 0 | 2 (2.7%) | ||
TDM1 | 0 | 0 | 0 | ||
None | 44 (88%) | 23 (92%) | 67 (89.3%) | ||
Chemotherapy-M1 non- CNS | |||||
Anti-microtubulee | 15 (30%) | 6 (24%) | 21(28%) | 0.489 | |
Platinum based | 1 (2%) | 2 (8%) | 3 (4%) | ||
Anthracycline based | 4 (8%) | 3 (12%) | 7 (9.3%) | ||
Capecitabine | 11 (22%) | 7 (28%) | 18 (24%) | ||
None | 19 (38) | 7 (28%) | 26 (34.7%) | ||
Hormonal therapy- M1 non-CNS | |||||
Tamoxifen | 0 | 1 (4%) | 1 (1.3%) | 0.506 | |
AIf | 2 (4%) | 3 (12%) | 5 (6.7%) | ||
Tamoxifen followed by AI | 2 (4%) | 0 | 2 (2.7%) | ||
Fulvestrant | 5 (10%) | 3 (12%) | 8 (10.7%) | ||
Anti-CDK4/6g+/− AI/ Fulvestrant | 10 (20%) | 4 (16%) | 14 (18.7%) | ||
None | 31 (62%) | 14 (56%) | 45 (60%) | ||
anti-HER2- M1 non-CNS | |||||
Trastuzumab | 4 (8%) | 0 | 4 (5.3%) | 0.282 | |
Trastuzumab+Pertuzumab | 5 (10%) | 6 (24%) | 11 (14.7%) | ||
TDM1 | 1 (2%) | 1 (4%) | 2 (2.7%) | ||
TKI basedh | 6 (12%) | 4 (16%) | 10 (13.3%) | ||
None | 34 (68%) | 14 (56%) | 48 (64%) | ||
Immunotherapy pre-CNS metastasisi | |||||
Yes | 2 (4%) | 0 | 2 (2.6%) | 0.598 | |
No | 48 (96%) | 25 (100%) | 73 (97.3%) | ||
No. treatment lines pre- CNS metastasis | |||||
No treatment for non- CNS metastasis | 12 (24%) | 2 (8%) | 14 (18.7%) | 0.269 | |
1st line | 19 (38%) | 7 (28%) | 26 (34.7%) | ||
2nd line | 6 (12%) | 5 (20%) | 11 (14.7%) | ||
3rd line | 7 (14%) | 6 (24%) | 13 (17.3%) | ||
4th line or later | 6 (12%) | 5 (20%) | 11 (14.7%) | ||
First site of systemic metastatic spread | |||||
Visceral | 17 (34%) | 10 (40%) | 27 (36%) | 0.843 | |
Bone | 6 (12%) | 2 (8%) | 8 (10.7%) | ||
CNS | 8 (16%) | 2 (8%) | 10 (13.3%) | ||
Simultaneous multiple non-CNS sites | 15 (30%) | 9 (36%) | 24 (32%) | ||
Simultaneous CNS + non-CNS | 4 (8%) | 2 (8%) | 6 (8%) | ||
No. of distant non-CNS metastatic sites | |||||
1 site | 6 (12%) | 2 (8%) | 8 (10.7%) | 0.969 | |
2 sites | 15 (30%) | 8 (32%) | 23 (30.7%) | ||
3–4 sites | 22 (17.1%) | 11 (44%) | 33 (44%) | ||
5–6 sites | 3 (6%) | 2 (8%) | 5 (6.7%) | ||
None | 4 (8%) | 2 (8%) | 6 (8%) | ||