Background
Methods
Results
Baseline characteristics and the incidence of liver metastases
Variable | Patients, No. % | |
---|---|---|
Total (n = 311,573) | With Liver Metastases (n = 4067) | |
Age, y | ||
18–40 | 21,313 (6.8%) | 494 (12.1%) |
41–60 | 137,299 (44.1%) | 1882 (46.3%) |
61–80 | 129,497 (41.6%) | 1414 (34.8%) |
> 80 | 23,464 (7.5%) | 277 (6.8%) |
Race | ||
White | 207,400 (66.6%) | 2565 (63.1%) |
Black | 35,062 (11.3%) | 737 (18.1%) |
Hispanic | 37,499 (12.0%) | 427 (10.5%) |
Asian or Pacific Islander | 27,997 (9.0%) | 305 (7.5%) |
American Indian/Alaska Native | 1757 (0.6%) | 23 (0.6%) |
Unknown | 1858 (0.6%) | 10 (0.2%) |
Marital status | ||
Unmarried a | 123,349 (39.6%) | 2011 (49.4%) |
Married | 171,728 (55.1%) | 1827 (44.9%) |
Unknown | 16,496 (5.3%) | 229 (5.6%) |
Insurance status | ||
Uninsured b | 5417 (1.7%) | 163 (4.0%) |
Insured | 300,400 (96.4%) | 3821 (94.0%) |
Unknown | 5756 (1.8%) | 83 (2.0%) |
Histology | ||
Infiltrating duct carcinoma | 234,958 (75.4%) | 2971 (73.1%) |
Lobular carcinoma | 27,050 (8.7%) | 246 (6.0%) |
Infiltrating duct and lobular carcinoma | 16,392 (5.3%) | 133 (3.3%) |
Other types c | 33,173 (10.6%) | 717 (17.6%) |
Pathological Grade | ||
I | 66,365 (21.3%) | 144 (3.5%) |
II | 129,786 (41.6%) | 1147 (28.2%) |
III/IV | 98,850 (31.7%) | 1939 (47.7%) |
Unknown | 16,572 (5.3%) | 837 (20.6%) |
Surgery of primary site | ||
Yes | 285,989 (91.8%) | 952 (23.4%) |
No | 22,831 (7.3%) | 3052 (75.0%) |
Unknown | 2753 (0.9%) | 63 (1.5%) |
Radiotherapy | ||
Yes | 162,703 (52.2%) | 1082 (26.6%) |
No/Unknown | 148,870 (47.8) | 2985 (73.4%) |
Chemotherapy | ||
Yes | 130,572 (42.0%) | 2802 (68.9%) |
No/Unknown | 181,001 (58.1%) | 1265 (31.1%) |
Extrahepatic metastatic sites to lung, brain and bone, No | ||
0 | 298,407 (95.8%) | 1060 (26.1%) |
1 | 9408 (3.0%) | 1696 (41.7%) |
2 | 2747 (0.9%) | 891 (21.9%) |
All 3 | 343 (0.1%) | 177 (4.4%) |
Unknown | 668 (0.2%) | 243 (6.0%) |
Subtype | ||
HR+/HER2− | 211,127 (67.8%) | 1612 (39.6%) |
HR+/HER2+ | 32,962 (10.6%) | 884 (21.7%) |
HR−/HER2+ | 14,089 (4.5%) | 601 (14.8%) |
Triple-negative | 33,352 (10.7%) | 544 (13.4%) |
Unknown | 20,043 (6.4%) | 426 (10.5%) |
Variable | Patients, No. % |
---|---|
Patients (n = 1728) | |
Age at diagnosis, y | |
21–40 | 288 (16.7%) |
41–60 | 1143 (66.1%) |
> 60 | 297 (17.2%) |
Histology | |
Infiltrating duct carcinoma | 1396 (80.8%) |
Lobular carcinoma | 31 (1.8%) |
Other | 301 (17.4%) |
De novo metastatic diseases | |
No | 1526 (88.3%) |
Yes | 202 (11.7%) |
Surgery of primary site | |
No | 219 (12.7%) |
Yes | 1509 (87.3%) |
Prior Chemotherapy | |
No | 226 (13.1%) |
Yes | 1502 (86.9%) |
Prior Radiotherapy | |
No | 848 (49.1%) |
Yes | 785 (45.4%) |
Unknown | 95 (5.5%) |
Recurrent sequence | |
First liver metastases | 1087 (62.9%) |
Subsequent liver metastases | 641 (37.1%) |
Extrahepatic metastatic sites to lung, brain, bone and lymph nodes, No | |
0 | 561 (32.5%) |
1 | 534 (30.9%) |
2 | 382 (22.1%) |
3 | 223 (12.9%) |
All 4 | 28 (1.6%) |
Subtype | |
HR+/HER2− | 767 (44.3%) |
HR+/HER2+ | 305 (17.7%) |
HR−/HER2+ | 321 (18.6%) |
Triple-negative | 270 (15.6%) |
Unknown | 65 (3.8%) |
Risk factors for liver metastasis
Variable | Among Entire Cohort | |
---|---|---|
Multivariate | ||
OR (95% CI) | P Value | |
Age at diagnosis, y | ||
18–40 | 1[Reference] | |
41–60 | 0.59 (0.54–0.66) | < 0.001* |
61–80 | 0.46 (0.41–0.51) | < 0.001* |
> 80 | 0.46 (0.40–0.54) | < 0.001* |
Race | ||
White | 1[Reference] | |
Black | 1.54 (1.41–1.67) | < 0.001* |
Hispanic | 0.82 (0.74–0.91) | < 0.001* |
Asian or Pacific Islander | 0.81 (0.72–0.92) | 0.001* |
American Indian/Alaska Native | 0.93 (0.59–1.38) | 0.725 |
Unknown | 0.38 (0.19–0.68) | < 0.001* |
Marital status | ||
Unmarried a | 1[Reference] | |
Married | 0.64 (0.60–0.68) | < 0.001* |
Unknown | 0.83 (0.72–0.96) | 0.013* |
Insurance status | ||
Uninsured b | 1[Reference] | |
Insured | 0.53 (0.45–0.63) | < 0.001* |
Unknown | 0.48 (0.35–0.67) | < 0.001* |
Histology | ||
Infiltrating duct carcinoma | 1[Reference] | |
Lobular carcinoma | 0.68 (0.59–0.77) | < 0.001* |
Infiltrating duct and lobular carcinoma | 0.66 (0.55–0.79) | < 0.001* |
Other types c | 1.25 (1.14–1.37) | < 0.001* |
Pathological Grade | ||
I | 1[Reference] | |
II | 3.89 (3.28–4.65) | < 0.001* |
III/IV | 8.59 (7.26–10.23) | < 0.001* |
Unknown | 20.75 (17.32–25.02) | < 0.001* |
Extrahepatic metastatic sites to lung, brain and bone, No | ||
0 | 1[Reference] | |
1 | 58.49 (53.84–63.57) | < 0.001* |
2 | 123.15 (110.89–136.76) | < 0.001* |
All 3 | 246.17 (195.34–310.33) | < 0.001* |
Unknown | 299.10 (240.01–372.94) | < 0.001* |
Subtype | ||
HR+/HER2− | 1[Reference] | |
HR+/HER2+ | 3.13 (2.87–3.41) | < 0.001* |
HR−/HER2+ | 4.75 (4.30–5.25) | < 0.001* |
Triple-negative | 1.92 (1.73–2.12) | < 0.001* |
Unknown | 1.48 (1.31–1.68) | < 0.001* |
Survival and prognostic factors
Variable | Overall Survival | |||
---|---|---|---|---|
Univariable | Multivariable | |||
HR (95% CI) | P Value | HR (95% CI) | P Value | |
Age, y | ||||
18–40 | 1[Reference] | 1[Reference] | ||
41–60 | 1.52 (1.32–1.76) | < 0.001* | 1.39 (1.20–1.61) | < 0.001* |
61–80 | 2.17 (1.88–2.51) | < 0.001* | 1.84 (1.58–2.15) | < 0.001* |
> 80 | 4.44 (3.65–5.39) | < 0.001* | 3.62 (2.76–4.74) | < 0.001* |
Race a | ||||
White | 1[Reference] | 1[Reference] | ||
Black | 1.21 (1.09–1.33) | < 0.001* | 1.35 (1.22–1.50) | < 0.001* |
Hispanic | 0.99 (0.87–1.13) | 0.895 | 1.16 (1.02–1.32) | 0.028* |
Asian or Pacific Islander | 0.86 (0.74–1.02) | 0.078 | 0.90 (0.76–1.05) | 0.182 |
American Indian or Alaska Native | 0.96 (0.58–1.59) | 0.869 | 1.01 (0.60–1.68) | 0.984 |
Unknown | 0.34 (0.09–1.37) | 0.129 | 0.28 (0.07–1.15) | 0.078 |
Marital status | ||||
Unmarried a | 1[Reference] | 1[Reference] | ||
Married | 0.75 (0.70–0.82) | < 0.001* | 0.84 (0.77–0.91) | < 0.001* |
Unknown | 0.96 (0.81–1.14) | 0.664 | 0.89 (0.75–1.06) | 0.200 |
Insurance status | ||||
Uninsured b | 1[Reference] | 1[Reference] | ||
Insured | 0.75 (0.62–0.91) | 0.003* | 0.71 (0.59–0.86) | < 0.001* |
Unknown | 0.94 (0.68–1.30) | 0.717 | 0.83 (0.57–1.22) | 0.348 |
Histology | ||||
Infiltrating duct carcinoma | 1[Reference] | 1[Reference] | ||
Lobular carcinoma | 1.14 (0.97–1.34) | 0.112 | 0.87 (0.74–1.03) | 0.101 |
Infiltrating duct and lobular carcinoma | 0.94 (0.68–1.30) | 0.717 | 0.89 (0.70–1.13) | 0.323 |
Other types c | 1.43 (1.30–1.58) | < 0.001* | 1.18 (1.05–1.33) | 0.005* |
Pathological Grade | ||||
I | 1[Reference] | 1[Reference] | ||
II | 1.08 (0.86–1.37) | 0.515 | 1.35 (1.07–1.72) | 0.013* |
III/IV | 1.30 (1.04–1.64) | 0.022* | 1.69 (1.34–2.14) | < 0.001* |
Unknown | 1.59 (1.26–1.01) | < 0.001* | 1.59 (1.23–2.05) | < 0.001* |
Surgery of primary site | ||||
Yes | 1[Reference] | 1[Reference] | ||
No | 1.72 (1.56–1.89) | < 0.001* | 1.52 (1.38–1.68) | < 0.001* |
Unknown | 0.93 (0.62–1.38) | < 0.001* | 0.96 (0.64–1.43) | < 0.001* |
Radiotherapy | ||||
Yes | 1[Reference] | 1[Reference] | ||
No/Unknown | 1.03 (0.94–1.12) | 0.528 | 0.95 (0.87–1.04) | 0.270 |
Chemotherapy | ||||
Yes | 1[Reference] | 1[Reference] | ||
No/Unknown | 2.03 (1.87–2.20) | < 0.001* | 1.63 (1.50–1.78) | < 0.001* |
Extrahepatic metastatic sites to lung, brain and bone, No | ||||
0 | 1[Reference] | 1[Reference] | ||
1 | 1.49 (1.34–1.65) | < 0.001* | 1.42 (1.28–1.58) | < 0.001* |
2 | 1.94 (1.73–2.18) | < 0.001* | 1.85 (1.65–2.09) | < 0.001* |
All 3 | 2.94 (2.44–3.56) | < 0.001* | 3.43 (2.77–4.26) | < 0.001* |
Unknown | 1.92 (1.62–2.28) | < 0.001* | 1.62 (1.36–1.93) | < 0.001* |
Subtype | ||||
HR+/HER2− | 1[Reference] | 1[Reference] | ||
HR+/HER2+ | 0.59 (0.53–0.66) | < 0.001* | 0.69 (0.61–0.77) | < 0.001* |
HR−/HER2+ | 0.72 (0.63–0.82) | < 0.001* | 0.85 (0.74–0.97) | 0.014* |
Triple-negative | 2.10 (1.88–2.35) | < 0.001* | 2.46 (2.18–2.77) | < 0.001* |
Unknown | 1.54 (1.36–1.74) | < 0.001* | 1.38 (1.20–1.58) | < 0.001* |
Variable | Overall Survival | |||
---|---|---|---|---|
Univariate | Multivariate | |||
HR (95% CI) | P Value | HR (95% CI) | P Value | |
Age at diagnosis, y | ||||
21–40 | 1[Reference] | 1[Reference] | ||
41–60 | 1.34 (1.11–1.62) | 0.003* | 1.38 (1.09–1.74) | 0.006* |
> 60 | 1.39 (1.10–1.75) | 0.005* | 1.55 (0.86–2.80) | 0.145 |
Histology | ||||
Infiltrating duct carcinoma | 1[Reference] | 1[Reference] | ||
Lobular carcinoma | 0.90 (0.56–1.43) | 0.648 | 0.68 (0.41–1.14) | 0.146 |
Other | 0.72 (0.60–0.87) | < 0.001* | 1.05 (0.85–1.29) | 0.661 |
De novo metastatic diseases | ||||
No | 1[Reference] | 1[Reference] | ||
Yes | 0.40 (0.31–0.52) | < 0.001* | 0.67 (0.29–1.52) | 0.337 |
Surgery of primary site | ||||
No surgery | 1[Reference] | 1[Reference] | ||
Yes | 2.33 (1.83–2.98) | < 0.001* | 1.02 (0.50–2.09) | 0.947 |
Prior Chemotherapy | ||||
No | 1[Reference] | 1[Reference] | ||
Yes | 2.56 (1.99–3.28) | < 0.001* | 1.51 (0.88–2.60) | 0.135 |
Prior Radiotherapy | ||||
No | 1[Reference] | 1[Reference] | ||
Yes | 1.33 (1.17–1.51) | < 0.001* | 1.20 (1.04–1.39) | 0.014* |
Unknown | 0.77 (0.54–1.08) | 0.122 | 0.67 (0.45–0.99) | 0.046* |
Recurrent sequence | ||||
First liver metastases | 1[Reference] | 1[Reference] | ||
Subsequent liver metastases | 2.16 (1.90–2.46) | < 0.001* | 1.58 (1.33–1.87) | < 0.001* |
Extrahepatic metastatic sites to lung, brain, bone and lymph nodes, No | ||||
0 | 1[Reference] | 1[Reference] | ||
1 | 1.54 (1.30–1.83) | < 0.001* | 1.16 (0.95–1.41) | 0.15 |
2 | 2.16 (1.80–2.59) | < 0.001* | 1.56 (1.23–1.97) | < 0.001* |
3 | 2.57 (2.08–3.18) | < 0.001* | 2.05 (1.51–2.79) | < 0.001* |
All 4 | 5.49 (3.56–8.47) | < 0.001* | 4.59 (2.42–8.69) | < 0.001* |
Subtype | ||||
HR+/HER2− | 1[Reference] | 1[Reference] | ||
HR+/HER2+ | 0.82 (0.68–0.98) | 0.033* | 1.02 (0.83–1.25) | 0.851 |
HR−/HER2+ | 0.84 (0.70–1.01) | 0.067 | 1.13 (0.92–1.40) | 0.242 |
Triple-negative | 1.83 (1.53–2.20) | < 0.001* | 2.17 (1.78–2.63) | < 0.001* |
Unknown | 1.11 (0.79–1.57) | 0.544 | 1.63 (1.10–2.43) | 0.015* |
HER2-targeted therapy
Variable | Overall Survival With HER2-targeted therapy | Overall Survival Without HER2-targeted therapy | ||
---|---|---|---|---|
HR (95% CI) | P Value | HR (95% CI) | P Value | |
Subtype | ||||
HR+/HER2− | 1[Reference] | 1[Reference] | ||
HR+/HER2+ | 0.74 (0.58–0.95) | 0.017* | 2.62 (1.88–3.66) | < 0.001* |
HR−/HER2+ | 0.81 (0.63–1.05) | 0.110 | 3.43 (2.29–5.15) | < 0.001* |
Triple-negative | 2.17 (1.78–2.63) | < 0.001* | 2.17 (1.78–2.63) | < 0.001* |