Baseline Characteristics
Out of n = 2,610,598 patients identified with BC in the NCDB between 2010 and 2020, n = 9,005 (0.34%) patients had de novo BM. Table 1 outlines the baseline characteristics of this cohort across the different treatment combinations received. Most patients with de novo BM were in the 61–70 age (30.3%) compared to the lowest proportion in the ≤ 50 age group (20.6%). Most patients were female (98.9%), of White race (76.6%), and non–Hispanic ethnicity (92.4%). Most patients were treated at either Comprehensive Community Cancer Programs (CCCP) (39.2%) or Academic/Research Programs (35.5%). In this database, most patients had insurance with only 7.5% of the cohort being un–insured. Most patients had a CDS of 0 (79.7%) with only 2.6% having a score of ≥ 3. There was a trend of increasing BCBM diagnosis during the 11–year span ranging from 7.7% in 2010 to 10.2% in 2020. Most BC cases had invasive ductal histology (64.9%), were poorly differentiated (43.4%), and ≥ 3 cm in size (62.8%). The BC subtype proportions in this cohort were as follows: 48% HR(+)/HER2(–), 22.6% HR(–)/HER2(–), 16.8% HR(+)/HER2(+), and 12.6% HR(–)/HER2(+). Based on the number of EMS, 15.7%, 31.3%, 27.9%, and 25.1% of the cohort had 0, 1, 2, and ≥ 3 EMS, respectively. 17.7% of the patients did not receive treatment for either BC or BM, 9.5% received treatment for BM only, 33.6% received treatment for BC only, and 39.1% received treatment for both BC and BM. All variables except sex, ethnicity, facility type, year of diagnosis, and lympho–vascular invasion were significantly associated with the treatment combination received (p < 0.005).
Table 1
Baseline demographics and breast cancer-related variables with group comparisons across the different treatments received.
Variable | Categories | Overall | No Treatment for Both | Treatment for BM Only | Treatment for BC Only | Treatment for Both | p-value | |
N (%) | | 9005 (100) | 1594 (17.7%) | 859 (9.5%) | 3027 (33.6%) | 3525 (39.1%) | | |
Age (years) N (%) | ≤ 50 | 1854 (20.6) | 187 (11.7) | 123 (14.3) | 691 (22.8) | 853 (24.2) | < 0.001 | |
51–60 | 2510 (27.9) | 341 (21.4) | 232 (27.0) | 873 (28.8) | 1064 (30.2) | |
61–70 | 2732 (30.3) | 470 (29.5) | 276 (32.1) | 912 (30.1) | 1074 (30.5) | |
≥ 70 | 1909 (21.2) | 596 (37.4) | 228 (26.5) | 551 (18.2) | 534 (15.1) | |
Sex N (%) | Female | 8904 (98.9) | 1577 (98.9) | 852 (99.2) | 2993 (98.9) | 3482 (98.8) | 0.7821 | |
Male | 101 (1.1) | 17 (1.1) | 7 (0.8) | 34 (1.1) | 43 (1.2) | |
Race N (%), n = 8919 | Black | 1671 (18.7) | 329 (20.9) | 187 (22.1) | 522 (17.4) | 633 (18.1) | 0.0071 | |
Other | 415 (4.7) | 69 (4.4) | 32 (3.8) | 154 (5.1) | 160 (4.6) | | |
White | 6833 (76.6) | 1177 (74.7) | 628 (74.1) | 2329 (77.5) | 2699 (77.3) | | |
Ethnicity N (%), n = 8764 | Hispanic | 664 (7.6) | 106 (6.9) | 61 (7.3) | 241 (8.2) | 256 (7.5) | 0.4304 | |
Non-Hispanic | 8100 (92.4) | 1434 (93.1) | 778 (92.7) | 2707 (91.8) | 3181 (92.5) | | |
Insurance status N (%), n = 8768 | Medicaid | 1439 (16.4) | 206 (13.4) | 114 (13.7) | 512 (17.4) | 607 (17.6) | < 0.0001 | |
Medicare | 3332 (38.0) | 800 (51.9) | 400 (48.0) | 1025 (34.9) | 1107 (32.0) | | |
Not Insured | 655 (7.5) | 144 (9.3) | 67 (8.0) | 215 (7.3) | 229 (6.6) | | |
Private Insurance / Managed Care | 3342 (38.1) | 391 (25.4) | 253 (30.3) | 1183 (40.3) | 1515 (43.8) | | |
Facility Type N (%), n = 8449 | Academic/Research Program | 3003 (35.5) | 495 (32.1) | 300 (35.8) | 998 (35.8) | 1210 (36.8) | 0.0976 | |
Community Cancer Program | 742 (8.8) | 149 (9.7) | 79 (9.4) | 253 (9.1) | 261 (8.0) | |
Comprehensive Community Cancer Program | 3315 (39.2) | 643 (41.7) | 323 (38.6) | 1085 (38.9) | 1264 (38.5) | |
Integrated Network Cancer Program | 1389 (16.4) | 254 (16.5) | 135 (16.1) | 451 (16.2) | 549 (16.7) | |
Median Income Quartiles 2012–2016 N (%), n = 8092 | <$40,227 | 1758 (21.7) | 337 (23.3) | 179 (23.2) | 581 (21.2) | 661 (21.0) | 0.0096 | |
$40,22-$50,353 | 1810 (22.4) | 327 (22.6) | 186 (24.1) | 580 (21.3) | 717 (22.8) | | |
$50,354-$63,332 | 1901 (23.5) | 354 (24.5) | 168 (21.8) | 609 (22.3) | 770 (24.5) | | |
>$63,333 | 2623 (32.4) | 428 (29.6) | 238 (30.9) | 960 (35.2) | 997 (31.7) | | |
Percent No High School Degree Quartiles 2012–2016 N (%), n = 8112 | < 6.3% | 1675 (20.6) | 265 (18.3) | 138 (17.8) | 602 (22.0) | 670 (21.2) | 0.0025 | |
6.3%-10.8% | 2204 (27.2) | 382 (26.4) | 188 (24.3) | 751 (27.5) | 883 (28.0) | | |
10.9%-17.5% | 2189 (27.0) | 402 (27.8) | 224 (28.9) | 730 (26.7) | 833 (26.4) | | |
> 17.6% | 2044 (25.2) | 398 (27.5) | 224 (28.9) | 651 (23.8) | 771 (24.4) | | |
Year of Diagnosis N (%) | 2010 | 696(7.7) | 127(8.0) | 72(8.4) | 240(7.9) | 257(7.3) | 0.1797 | |
2011 | 741(8.2) | 135(8.5) | 80(9.3) | 238(7.9) | 288(8.2) | | |
2012 | 728(8.1) | 132(8.3) | 73(8.5) | 261(8.6) | 262(7.4) | | |
2013 | 756(8.4) | 117(7.3) | 74(8.6) | 271(9.0) | 294(8.3) | | |
2014 | 806(9.0) | 123(7.7) | 71(8.3) | 293(9.7) | 319(9.1) | | |
2015 | 851(9.5) | 150(9.4) | 77(9.0) | 308(10.2) | 316(9.0) | | |
2016 | 845(9.4) | 163(10.2) | 60(7.0) | 269(8.9) | 353(10.0) | | |
2017 | 824(9.2) | 156(9.8) | 71(8.3) | 282(9.3) | 315(8.9) | | |
2018 | 916(10.1) | 171(10.7) | 88(10.2) | 289(9.5) | 368(10.4) | | |
2019 | 923(10.2) | 157(9.9) | 96(11.2) | 285(9.4) | 385(10.9) | | |
2020 | 919(10.2) | 163(10.2) | 97(11.2) | 291(9.6) | 368(10.4) | | |
Histology N (%) | Ductal | 5844 (64.9) | 851 (53.4) | 518 (60.3) | 2044 (67.5) | 2431 (69.0) | < 0.001 | |
Lobular | 590 (6.6) | 90 (5.6) | 39 (4.5) | 241 (8.0) | 220 (6.2) | | |
Other | 2571 (28.6) | 653 (41.0) | 302 (35.2) | 742 (24.5) | 874 (24.8) | | |
Grade N (%), n = 6085 | 1 | 916(15.1) | 131(14.8) | 61(11.8) | 383(17.4) | 341(13.7) | < 0.001 | |
2 | 2525(41.5) | 348(39.4) | 186(36.1) | 924(42.0) | 1067(43.0) | | |
3 | 2644(43.4) | 405(45.8) | 269(52.1) | 894(40.6) | 1076(43.3) | | |
Tumor Size N (%), n = 6561 | < 1 cm | 538 (8.2) | 74 (7.2) | 53 (8.8) | 175 (7.8) | 236 (8.8) | 0.0002 | |
1–2 cm | 909 (13.9) | 145 (14.0) | 105 (17.4) | 279 (12.3) | 380 (14.2) | | |
2–3 cm | 989 (15.1) | 148 (14.3) | 116 (19.3) | 360 (16.0) | 365 (13.7) | | |
> 3 cm | 4125 (62.8) | 666 (64.5) | 328 (54.5) | 1443 (63.9) | 1688 (63.2) | | |
Lympho-vascular Invasion N (%), n = 2711 | 0 | 1742(64.3) | 237(63.5) | 134(61.2) | 655(66.0) | 716(63.5) | 0.4583 | |
1 | 969(35.7) | 136(36.5) | 85(38.8) | 337(34.0) | 411(36.5) | | |
Charlson Deyo Score N (%) | 0 | 7178 (79.7) | 1196 (75.0) | 637 (74.2) | 2477 (81.8) | 2868 (81.4) | < 0.001 | |
1 | 1222 (13.6) | 232 (14.6) | 138 (16.1) | 401 (13.2) | 451 (12.8) | |
2 | 370 (4.1) | 91 (5.7) | 54 (6.3) | 90 (3.0) | 135 (3.8) | |
≥ 3 | 235 (2.6) | 75 (4.7) | 30 (3.5) | 59 (1.9) | 71 (2.0) | |
Breast Cancer Subtype N (%), n = 7563 | HR (-) / HER2 (-) | 1708 (22.6) | 319 (30.0) | 285 (42.3) | 422 (15.7) | 682 (21.7) | < 0.001 | |
HR (-) / HER2 (+) | 956 (12.6) | 122 (11.5) | 91 (13.5) | 285 (10.6) | 458 (14.6) | |
HR (+) / HER2 (-) | 3627 (48.0) | 482 (45.3) | 208 (30.9) | 1514 (56.4) | 1423 (45.3) | |
HR (+) / HER2 (+) | 1272 (16.8) | 140 (13.2) | 90 (13.3) | 464 (17.3) | 578 (18.4) | |
Number of Extracranial Metastatic Sites N (%), n = 8979 | Brain + 1 Metastatic Site | 2808 (31.3) | 476 (30.1) | 241 (28.3) | 1037 (34.3) | 1054 (29.9) | < 0.001 | |
Brain + 2 Metastatic Sites | 2504 (27.9) | 397 (25.1) | 211 (24.8) | 947 (31.3) | 949 (27.0) | |
Brain + ≥ 3 Metastatic Sites | 2258 (25.1) | 450 (28.5) | 175 (20.5) | 776 (25.7) | 857 (24.3) | |
Only Brain | 1409 (15.7) | 258 (16.3) | 225 (26.4) | 265 (8.7) | 661 (18.8) | |
Location of Extracranial Metastatic Sites N (%), n = 8979 | Bone | 1786 (19.8) | 283 (17.9) | 109 (12.8) | 799 (26.4) | 595 (16.9) | < 0.001 | |
Bone + Liver | 696 (7.8) | 102 (6.4) | 53 (6.2) | 314 (10.4) | 227 (6.5) | |
Bone + Liver + Lung | 908 (10.1) | 183 (11.6) | 63 (7.4) | 331 (10.9) | 331 (9.4) | |
Bone + Lung | 1038 (11.6) | 169 (10.7) | 71 (8.3) | 380 (12.6) | 418 (11.9) | |
Liver | 184 (2.1) | 30 (1.9) | 18 (2.1) | 61 (2.0) | 75 (2.1) | |
Liver + Lung | 264 (2.9) | 50 (3.2) | 36 (4.2) | 75 (2.5) | 103 (2.9) | |
Lung | 689 (7.7) | 141 (8.9) | 91 (10.7) | 137 (4.5) | 320 (9.1) | |
Only Brain | 1409 (15.7) | 258 (16.3) | 225 (26.4) | 265 (8.8) | 661 (18.8) | |
Other | 2005 (22.3) | 365 (23.1) | 186 (21.8) | 663 (21.9) | 791 (22.4) | |
Brain Metastasis Treatment Modality N (%), n = 9004 | No Treatment | 4620 (51.3) | 1594 (100.0) | 0 (0.0) | 3026 (100.0) | 0 (0.0) | < 0.001 | |
SRS | 827 (9.2) | 0 (0.0) | 122 (14.2) | 0 (0.0) | 705 (20.0) | |
WBRT | 2596 (28.8) | 0 (0.0) | 505 (58.7) | 0 (0.0) | 2091 (59.3) | |
Surgery | 445 (4.9) | 0 (0.0) | 150 (17.5) | 0 (0.0) | 295 (8.4) | |
Surgery + SRS | 311 (3.5) | 0 (0.0) | 53 (6.2) | 0 (0.0) | 258 (7.3) | |
Surgery + WBRT | 205 (2.3) | 0 (0.0) | 29 (3.4) | 0 (0.0) | 176 (5.0) | |
Breast Cancer Treatment Modality N (%), n = 8991 | No Treatment | 2439 (27.1) | 1586 (100.0) | 853 (100.0) | 0 (0.0) | 0 (0.0) | < 0.001 | |
Immunotherapy | 98 (1.1) | 0 (0.0) | 0 (0.0) | 49 (1.6) | 49 (1.4) | |
Chemotherapy | 2101 (23.4) | 0 (0.0) | 0 (0.0) | 894 (29.5) | 1207 (34.2) | |
Hormonal Therapy | 1434 (16.0) | 0 (0.0) | 0 (0.0) | 753 (24.9) | 681 (19.3) | |
Immunotherapy + Hormonal Therapy | 199 (2.2) | 0 (0.0) | 0 (0.0) | 112 (3.7) | 87 (2.5) | |
Chemotherapy + Hormonal Therapy | 1390 (15.5) | 0 (0.0) | 0 (0.0) | 695 (23.0) | 695 (19.7) | |
Chemotherapy + Immunotherapy | 912 (10.1) | 0 (0.0) | 0 (0.0) | 340 (11.2) | 572 (16.2) | |
Chemotherapy + Hormonal Therapy + Immunotherapy | 418 (4.6) | 0 (0.0) | 0 (0.0) | 184 (6.1) | 234 (6.6) | |
Median OS of the Cohort Across Different Variables
The median OS of the 9,005–patient cohort was 10.9 months (95% CI, 10.3–11.5). OS decreased significantly with increasing age, with highest OS observed in the ≤ 50 age group at 18.96 months (16.92–20.86) and the lowest in the ≥ 70 age group at 4.70 months (4.07–5.29) (log rank test, p < 0.0001). Patients treated at an Academic/Research Program had the highest OS amongst the different facilities at 13.63 months (12.19–15.00) (log rank test, p < 0.0001). OS decreased significantly with increasing CDS, with the highest OS in the group with a score of 0 at 12.42 months (11.76–13.17) and the lowest in the group with a score of ≥ 3 at 2.86 months (2.17–3.78) (log rank test, p < 0.0001). Across the four BC subgroups, the HR(+)/HER2(+) group had the highest OS at 22.05 months (18.73–24.67) compared to the lowest in the HR(–)/HER2(–) at 5.62 months (5.19–6.18) (log rank test, p < 0.0001). The HR(+)/HER2(–) and HR(–)/HER2(+) subgroups had similar OS at 15.80 months (14.46–17.15) and 14.59 months (11.79–16.95), respectively. There was a trend of worsening survival with increasing number of EMS, with the 1 EMS group having the highest OS at 13.17 months (12.02–14.36) compared to the group of with ≥ 3 EMS with lowest OS at 7.59 months (6.70–8.84) (log rank test, p < 0.0001). Based on the location of the EMS, bone metastasis conferred the highest OS amongst all combinations at 16.53 months (14.82–18.40) with the combined Liver and Lung group having the lowest OS at 5.22 months (3.09–6.34) (log rank test, p < 0.0001). Across the different local BM treatment modalities, patients without any treatment had the lowest OS at 9.26 months (8.31–10.02) compared to Surgery + WBRT group which had the highest OS at 32.33 months (23.98–40.44) (log rank test, p < 0.0001). Across the different BC treatment modalities, patients without any treatment had the lowest OS at 2.1 months (1.97–2.23) compared to the Chemotherapy + Hormonal Therapy + Immunotherapy group which had the highest OS at 42.35 months (35.48–54.14) (log rank test, p < 0.0001). Last, across the treatment combinations, the lowest OS was observed in the subgroup without any treatment at 1.77 months (1.64–1.97) followed by local treatment for BM only at 2.63 months (2.33–2.96). The subgroups that received BC treatment only and combination treatment for both brain and breast entities had similar OS at 16.92 months (16.00–18.27) and 16.30 months (15.11–17.38), respectively (log rank test, p < 0.0001). Table 2 summarizes the OS across the different variables, and Figs. 1–2 show the Kaplan–Meier curves with risk tables.
Table 2
Median overall survival (OS) across age, facility type, Charlson-Deyo Score, breast cancer subtype, number of extracranial metastatic sites, location of extracranial metastatic sites, brain metastasis treatment modality, breast cancer treatment modality, and treatment combinations.
Age | # of Cases | Median OS | 95% CI |
≤ 50 years | 1022/1501 | 18.96 | 16.92, 20.86 |
51–60 years | 1538/2054 | 12.98 | 11.89, 14.13 |
61–70 years | 1651/2183 | 10.55 | 9.50, 11.83 |
≥ 70 years | 1266/1523 | 4.70 | 4.07, 5.29 |
Total | 5477/7261 | | |
Log-rank test p-value | < .0001 | | |
Facility Type | | | |
Academic/research program | 1755/2445 | 13.63 | 12.19, 15.00 |
Community cancer program | 472/611 | 9.89 | 7.75, 11.37 |
Comprehensive community cancer program | 2097/2650 | 9.26 | 8.38, 9.89 |
Integrated network cancer program | 864/1117 | 9.26 | 8.02, 10.55 |
Total | 5188/6823 | | |
Log-rank test p-value | < .0001 | | |
Charlson Deyo Score | | | |
0 | 4251/5775 | 12.42 | 11.76, 13.17 |
1 | 821/1014 | 8.08 | 6.77, 9.56 |
2 | 249/291 | 4.90 | 3.38, 7.06 |
≥ 3 | 156/181 | 2.86 | 2.17, 3.78 |
Total | 5477/7261 | | |
Log-rank test p-value | < .0001 | | |
Breast Cancer Subtype | | | |
HR(-)/HER2(-) | 1194/1367 | 5.62 | 5.19, 6.18 |
HR(-)/HER2(+) | 547/767 | 14.59 | 11.79, 16.95 |
HR(+)/HER2(-) | 2132/2936 | 15.80 | 14.46, 17.15 |
HR(+)/HER2(+) | 655/998 | 22.05 | 18.73, 24.67 |
Total | 4528/6068 | | |
Log-rank test p-value | < .0001 | | |
Number of Extracranial Metastatic Sites | | | |
Only brain | 868/1200 | 12.00 | 10.38, 13.83 |
Brain + 1 metastatic site | 1798/2374 | 13.17 | 12.02, 14.36 |
Brain + 2 metastatic sites | 1562/2053 | 10.48 | 9.53, 11.83 |
Brain + ≥ 3 metastatic sites | 1232/1613 | 7.59 | 6.70, 8.84 |
Total | 5460/7240 | | |
Log-rank test p-value | < .0001 | | |
Location of Extracranial Metastatic Sites | | | |
Only Brain | 868/1200 | 12.00 | 10.38, 13.83 |
Bone | 1127/1529 | 16.53 | 14.82, 18.40 |
Liver | 133/161 | 6.37 | 4.57, 13.80 |
Lung | 470/586 | 8.38 | 7.29, 9.63 |
Bone + Liver | 467/595 | 10.12 | 7.79, 12.09 |
Bone + Lung | 712/931 | 11.99 | 10.28, 13.73 |
Liver + Lung | 200/232 | 5.22 | 3.09, 6.34 |
Bone + Liver + Lung | 671/805 | 6.83 | 5.49, 8.05 |
Other | 812/1201 | 9.56 | 8.08, 10.91 |
Total | 5460/7240 | | |
Log-rank test p-value | < .0001 | | |
Brain Metastasis Treatment Modality | | | |
No treatment | 2816/3729 | 9.26 | 8.31, 10.02 |
WBRT | 1725/2125 | 10.25 | 9.56, 11.10 |
SRS | 442/651 | 15.41 | 13.24, 18.53 |
Surgery | 246/358 | 19.81 | 14.78, 25.43 |
Surgery + SRS | 165/249 | 20.5 | 16.26, 23.98 |
Surgery + WBRT | 83/149 | 32.33 | 23.98, 40.44 |
Total | 5477/7261 | | |
Log-rank test p-value | < .0001 | | |
Breast Cancer Treatment Modality | | | |
No treatment | 1678/1955 | 2.10 | 1.97, 2.23 |
Immunotherapy | 60/74 | 5.00 | 3.32, 8.41 |
Chemotherapy | 1507/1817 | 10.50 | 9.86, 11.24 |
Hormonal Therapy | 967/1225 | 13.54 | 12.02, 15.11 |
Immunotherapy + Hormonal therapy | 103/154 | 23.69 | 17.74, 27.56 |
Chemotherapy + Hormonal Therapy | 680/1071 | 26.38 | 24.71, 28.55 |
Chemotherapy + Immunotherapy | 345/647 | 27.56 | 24.77, 33.31 |
Chemotherapy + Hormonal Therapy + Immunotherapy | 133/307 | 42.35 | 35.48, 54.14 |
Total | 5473/7250 | | |
Log-rank test p-value | < .0001 | | |
Treatment Combination | | | |
No treatment for both | 1082/1275 | 1.77 | 1.64, 1.97 |
Treatment for brain metastasis only | 600/691 | 2.63 | 2.33, 2.96 |
Treatment for breast cancer only | 1734/2454 | 16.92 | 16.00, 18.27 |
Treatment for both | 2061/2841 | 16.30 | 15.11, 17.38 |
Total | 5477/7261 | | |
Log-rank test p-value | < .0001 | | |
Median OS by Treatment Modality Across BC Subtypes
Based on BM treatment modality, the Surgery + WBRT groups achieved the highest OS across three BC subgroups at 33.35 (24.48–40.87), 48.85 (10.41–,), and 15.8 (6.31–21.98), in the HR(+)/HER2(–), HR(–)/HER2(+), and HR(–)/HER2(–) subgroups, respectively. For the HR(+)/HER2(+) subgroup, computing the Surgery + WBRT value was not possible, and Surgery + SRS achieve the highest OS at 42.25 (12.98–,) (log rank test, p < 0.0001). Based on BC treatment modality, the Chemotherapy + Hormonal therapy + Immunotherapy groups achieved the highest OS across three BC subgroups at 55.13 (35.58–,), 42.35 (36.04–55.36), and 31.34 (7.82–,), for the HR(+)/HER2(–), HR(+)/HER2(+), and HR(–)/HER2(+) subgroups, respectively. For the HR(–)/HER2(–) subgroup, Chemotherapy + Immunotherapy achieved the highest OS at 11.7 (9.46–16.72) (log rank test, p < 0.0001). Based on treatment combinations, receiving local and systemic treatment combined for both BM and BC achieved the highest OS at 19.02 (17.08–20.70), 28.94 (24.77–35.29), 19.42 (16.95–23.36), and 8.84 (7.85–9.79) for the HR(+)/HER2(–), HR(+)/HER2(+), HR(–)/HER2(+), and HR(–)/HER2(–) subgroups, respectively (log rank test, p < 0.0001). Table 3 summarizes the OS across the four BC subgroups, and supplementary Figs. 3–6 show the Kaplan–Meier curves with risk tables.
Table 3
Median overall survival (OS) for the four breast cancer subgroups across the different treatment modalities.
BC Subtype | HR(+)/HER2(-) | HR(+)/HER2(+) | HR(-)/HER2(+) | HR(-)/HER2(-) |
BM Treatment Modality | # of Cases | OS | 95% CI | # of Cases | OS | 95% CI | # of Cases | OS | 95% CI | # of Cases | OS | 95% CI |
No treatment | 1155/1615 | 14.88 | 13.17, 17.02 | 323/477 | 17.74 | 14.09, 22.34 | 237/329 | 11.56 | 7.85, 16.20 | 528/597 | 4.5 | 3.81, 5.03 |
WBRT | 613/767 | 13.08 | 10.87, 14.39 | 240/331 | 18.83 | 14.23, 22.77 | 208/278 | 15.74 | 12.58, 18.43 | 452/498 | 6.08 | 5.36, 6.87 |
SRS | 174/257 | 18.53 | 13.86, 22.77 | 48/97 | 39.79 | 28.75, . | 51/84 | 16.82 | 10.45, 30.65 | 107/134 | 8.5 | 5.49, 12.35 |
Surgery | 109/159 | 25.43 | 19.35, 30.72 | 21/39 | 35.98 | 14.36, 53.26 | 25/34 | 10.02 | 4.80, 19.55 | 41/51 | 6.7 | 4.27, 11.37 |
Surgery + SRS | 52/87 | 28.12 | 19.84, 44.09 | 17/33 | 42.25 | 12.98, . | 18/25 | 24.08 | 5.30, 59.17 | 43/53 | 7.46 | 4.44, 16.16 |
Surgery + WBRT | 29/51 | 33.35 | 24.48, 40.87 | 6/21 | . | 29.11, . | 8/17 | 48.85 | 10.41, . | 23/34 | 15.8 | 6.31, 21.98 |
Total | 2132/2936 | | | 655/998 | | | 547/767 | | | 1194/1367 | | |
Log-rank test p-value | < .0001 | < .0001 | 0.0209 | < 0.0001 |
BC Treatment Modality | | | | | | | | | | | | |
No treatment | 463/565 | 2.69 | 2.43, 3.32 | 143/174 | 2.56 | 1.94, 3.02 | 130/152 | 1.77 | 1.45, 2.20 | 441/481 | 2.07 | 1.91, 2.30 |
Immunotherapy (I) | 4/6 | 18.34 | 1.87, . | 19/21 | 4.17 | 2.14, 14.75 | 26/32 | 3.94 | 2.90, 6.05 | 3/6 | . | 1.45, . |
Chemotherapy (C) | 340/433 | 12.48 | 10.87, 14.88 | 110/137 | 18.83 | 11.53,23.49 | 205/254 | 15.51 | 12.16, 17.77 | 683/792 | 8.51 | 7.66, 9.23 |
Hormonal Therapy (H) | 746/957 | 15.38 | 13.54,18.20 | 63/70 | 5.6 | 3.22, 9.03 | 5/6 | 0.81 | 0.39, . | 11/12 | 3.33 | 0.90, 16.46 |
I + H | 46/73 | 31.54 | 24.51, 35.38 | 44/65 | 18 | 10.15, 23.36 | 3/4 | 7.36 | 1.35, . | | --- | --- |
C + H | 481/785 | 26.91 | 25.36, 29.14 | 92/134 | 31.57 | 20.96, 40.31 | 13/13 | 14.16 | 6.01, 24.90 | 17/22 | 10.68 | 6.77, 27.24 |
C + I | 20/31 | 14.42 | 8.90, 27.07 | 104/209 | 36.37 | 27.50, 51.52 | 156/291 | 30.65 | 22.97, 35.45 | 39/53 | 11.7 | 9.46, 16.72 |
C + H + I | 31/83 | 55.13 | 35.58, . | 77/184 | 42.35 | 36.04, 55.36 | 14-Sep | 31.34 | 7.82, . | | --- | ---- |
Total | 2131/2933 | | | 652/994 | | | 547/766 | | | 1194/1366 | | |
Log-rank test p-value | < .0001 | < .0001 | < .0001 | < .0001 |
Treatment Combination | | | | | | | | | | | | |
Neither BM nor BC | 321/398 | 2.56 | 2.10, 3.32 | 85/106 | 2.27 | 1.74, 2.70 | 77/90 | 1.51 | 1.15, 2.0 | 232/248 | 1.87 | 1.58, 2.07 |
Only BM | 143/170 | 3.25 | 2.50, 4.57 | 61/72 | 3.15 | 1.87, 5.26 | 53/63 | 2.07 | 1.64, 3.48 | 209/234 | 2.3 | 2.07, 2.63 |
Only BC | 834/1217 | 22.24 | 18.96, 24.77 | 238/371 | 24.67 | 21.19, 28.68 | 160/239 | 19.02 | 14.88, 23.16 | 296/349 | 8.57 | 7.33, 9.89 |
BM + BC | 834/1151 | 19.02 | 17.08, 20.70 | 271/449 | 28.94 | 24.77, 35.29 | 257/375 | 19.42 | 16.95, 23.36 | 457/536 | 8.84 | 7.85, 9.79 |
Total | 2132/2936 | | | 655/998 | | | 547/767 | | | 1194/1367 | | |
Log-rank test p-value | < .0001 | < .0001 | < .0001 | < .0001 |
Cox Regression Model
Univariate analyses were performed on 14 explanatory variables, and significant variables were computed to a multivariate cox regression model to find hazard ratios [HR (95% CI), p–value]. On multivariate analysis, older age was associated with increased risk of death. Compared to ≤ 50–year age–group, the 51–60 year and ≥ 70–year age groups had higher risk of death [1.17(1.04–1.31), p = 0.0099)] and [1.53(1.31–1.79), p < 0.0001], respectively. Patients with races other than White had lower risk of death compared to White patients [0.78(0.63–0.96), p = 0.0216]. Hispanic patients had lower risk of death compared to non–Hispanic patients [0.72(0.60–0.86), p = 0.0003]. Compared to patients with private insurance, those who were un–insured [1.38(1.18–1.61), p < 0.0001], on Medicaid [1.28(1.14–1.43), p < 0.0001], and on Medicare [1.20(1.07–1.34), p = 0.0013] had higher risks of death. Patients with a median income of ˂$40,227 had higher risk of death compared to ˃$63,333 [1.22(1.06–1.40), p = 0.0058], while high school degree was not significantly associated with survival. Compared to academic/research program facilities, CCCP [1.15(1.05–1.26), p = 0.0018], and integrated network cancer programs [1.21(1.08–1.36), p = 0.0012] had higher risks of death. Compared to patients with no comorbidities, higher CDS correlated with higher risks of death at [1.13(1.02–1.26), p = 0.0249], [1.32(1.09–1.60), p = 0.0041], and [1.74(1.39–2.18), p < 0.0001] for the 1, 2, and ≥ 3 score groups, respectively. Compared to patients diagnosed in 2018–2020, those diagnosed earlier in 2010–2011 [1.25(1.08–1.45), p = 0.0029] and 2014–2015 [1.20(1.03–1.39), p = 0.0164] had higher risk of death. The three BC subgroups had lower risk of death compared to the triple negative group, with the HR(+)/HER2(+) group having the best outcome with the lowest risk [0.43(0.38–0.49), p < 0.0001]. The location and number of EMS was significantly correlated with survival. Compared to only brain, bone + liver + lung [2.06(1.78–2.38), p < 0.0001] had the highest risk of death, followed by liver + lung [1.97(1.59–2.44), p < 0.0001], bone + liver [1.96(1.67–2.31), p < 0.0001], liver [1.88(1.45–2.45), p < 0.0001], other combinations [1.85(1.58–2.18), p < 0.0001], bone + lung [1.41(1.21–1.63), p < 0.0001], lung [1.31(1.12–1.53), p = 0.0009], and bone [1.31(1.15–1.49), p < 0.0001]. Compared to patients who received treatment for both breast and brain entities, patients who had no treatment for either [2.65(2.36–2.98), p < 0.0001] and treatment for BM only [2.30(2.00–2.63), p < 0.0001] were significantly more likely to die. Treatment for BC only was not statistically significant (p = 0.0920). Table 4 summarizes the results of the univariate and multivariate cox regression models.
Table 4
Univariate and multivariate cox regression models for variables predicting risk of death in the patient cohort.
Cox Regression Model | Univariate | Multivariate |
Variable | HR (95% CI) | p-value | HR (95% CI) | p-value |
Age | | | | |
≤ 50 years (ref) | 1 | - | 1 | - |
51–60 | 1.25(1.16–1.36) | < 0.0001 | 1.17(1.04–1.31) | 0.0099 |
61–70 | 1.36(1.26–1.47) | < 0.0001 | 1.11(0.98–1.27) | 0.0935 |
≥ 70 | 2.05(1.88–2.22) | < 0.0001 | 1.53(1.31–1.79) | < 0.0001 |
Sex | | | | |
Female (ref.) | 1 | - | | |
Male | 1.15(0.90–1.46) | 0.2751 | | |
Race | | | | |
White (ref.) | 1 | - | 1 | - |
Black | 1.09(1.02–1.16) | 0.0167 | 1.04(0.94–1.15) | 0.4849 |
Other | 0.76(0.66–0.88) | 0.0002 | 0.78(0.63–0.96) | 0.0216 |
Ethnicity | | | | |
Non-Hispanic (ref.) | 1 | - | 1 | - |
Hispanic | 0.65(0.58–0.73) | < 0.0001 | 0.72(0.60–0.86) | 0.0003 |
Insurance Status | | | | |
Private insurance/managed care (ref.) | 1 | - | 1 | - |
Not insured | 1.37(1.23–1.52) | < 0.0001 | 1.38(1.18–1.61) | < 0.0001 |
Medicaid | 1.17(1.08–1.27) | 0.0002 | 1.28(1.14–1.43) | < 0.0001 |
Medicare | 1.57(1.48–1.68) | < 0.0001 | 1.20(1.07–1.34) | 0.0013 |
Median Income Quartiles (2012–2016) | | | | |
˃$63,333 (ref.) | 1 | - | 1 | - |
$50,354-$63,332 | 1.12(1.04–1.21) | 0.0022 | 1.10(0.98–1.23) | 0.1031 |
$40,227 - $50,353 | 1.16(1.07–1.25) | 0.0002 | 1.11(0.98–1.26) | 0.0924 |
˂$40,227 | 1.17(1.08–1.26) | < 0.0001 | 1.22(1.06–1.40) | 0.0058 |
Percent no High School Degree Quartiles (2012–2016) | | | | |
< 6.3% (ref.) | 1 | - | 1 | - |
6.3%-10.8% | 1.08(1.00-1.17) | 0.053 | 1.02(0.90–1.14) | 0.7999 |
10.9%-17.5% | 1.16(1.07–1.26) | 0.0004 | 1.05(0.92–1.20) | 0.4946 |
> 17.6% | 1.05(0.97–1.14) | 0.2211 | 0.90(0.77–1.05) | 0.1804 |
Facility Type | | | | |
Academic/Research program (ref.) | 1 | - | 1 | - |
Community Cancer Program | 1.21(1.09–1.34) | 0.0002 | 1.06(0.92–1.22) | 0.3907 |
Comprehensive Community Cancer Program | 1.24(1.16–1.32) | < 0.0001 | 1.15(1.05–1.26) | 0.0018 |
Integrated Network Cancer Program | 1.26(1.16–1.37) | < 0.0001 | 1.21(1.08–1.36) | 0.0012 |
Charlson Deyo Score | | | | |
0 (ref.) | 1 | - | 1 | - |
1 | 1.26(1.17–1.36) | < 0.0001 | 1.13(1.02–1.26) | 0.0249 |
2 | 1.65(1.45–1.88) | < 0.0001 | 1.32(1.09–1.60) | 0.0041 |
≥ 3 | 1.92(1.63–2.25) | < 0.0001 | 1.74(1.39–2.18) | < 0.0001 |
Year of Diagnosis | | | | |
2010 | 1.32(1.18–1.49) | < 0.0001 | | |
2011 | 1.23(1.10–1.38) | 0.0004 | | |
2012 | 1.16(1.04–1.31) | 0.0108 | | |
2013 | 1.15(1.03–1.30) | 0.0156 | | |
2014 | 1.19(1.06–1.33) | 0.0033 | | |
2015 | 1.10(0.98–1.24) | 0.0965 | | |
2016 | 1.10(0.98–1.24) | 0.1067 | | |
2017 | 1.00(1.00–1.00) | . | | |
2018 | 1.13(1.01–1.27) | 0.0385 | | |
2019 | 1.00(1.00–1.00) | . | | |
2020 (ref.) | 1 | - | | |
Year of Diagnosis (Regrouped) | | | | |
2010–2011 | 1.20(1.10–1.30) | < 0.0001 | 1.25(1.08–1.45) | 0.0029 |
2012–2013 | 1.09(1.00-1.18) | 0.044 | 1.05(0.91–1.22) | 0.4896 |
2014–2015 | 1.08(0.99–1.16) | 0.0774 | 1.20(1.03–1.39) | 0.0164 |
2016–2017 | 1.04(0.94–1.15) | 0.5058 | 1.02(0.87–1.19) | 0.8482 |
2018–2020 (ref.) | 1 | - | 1 | - |
Histology | | | | |
Ductal (ref.) | 1 | - | | |
Lobular | 1.03(0.92–1.14) | 0.6592 | | |
Other | 1.20(1.13–1.27) | < 0.0001 | | |
Grade | | | | |
1 (ref.) | 1 | - | 1 | |
2 | 1.15(1.03–1.28) | 0.0124 | 1.04(0.91–1.19) | 0.547 |
3 | 1.40(1.26–1.56) | < 0.0001 | 1.16(1.00-1.35) | 0.0551 |
Tumor Size | | | | |
> 3 cm(ref.) | 1 | - | | |
2–3 cm | 1.02(0.93–1.11) | 0.73 | | |
1–2 cm | 1.02(0.93–1.12) | 0.6889 | | |
< 1 cm | 0.99(0.89–1.11) | 0.8897 | | |
Lympho-Vascular Invasion | | | | |
0 (ref.) | 1 | - | | |
1 | 1.01(0.92–1.11) | 0.8672 | | |
Breast Cancer Subtype | | | | |
HR(-)/HER2(-) (ref.) | 1 | - | 1 | - |
HR(-)/HER2(+) | 0.52(0.47–0.58) | < 0.0001 | 0.58(0.51–0.66) | < 0.0001 |
HR(+)/HER2(-) | 0.51(0.48–0.55) | < 0.0001 | 0.54(0.49–0.60) | < 0.0001 |
HR(+)/HER2(+) | 0.41(0.37–0.45) | < 0.0001 | 0.43(0.38–0.49) | < 0.0001 |
Location of Extracranial Metastatic Sites | | | | |
Only brain (ref.) | 1 | - | 1 | - |
Bone | 0.96(0.88–1.05) | 0.3799 | 1.31(1.15–1.49) | < 0.0001 |
Bone + Liver | 1.22(1.09–1.37) | 0.0005 | 1.96(1.67–2.31) | < 0.0001 |
Bone + Liver + Lung | 1.44(1.30–1.60) | < 0.0001 | 2.06(1.78–2.38) | < 0.0001 |
Bone + Lung | 1.07(0.97–1.19) | 0.1576 | 1.41(1.21–1.63) | < 0.0001 |
Liver | 1.27(1.06–1.52) | 0.0107 | 1.88(1.45–2.45) | < 0.0001 |
Liver + Lung | 1.73(1.48–2.02) | < 0.0001 | 1.97(1.59–2.44) | < 0.0001 |
Lung | 1.34(1.20–1.50) | < 0.0001 | 1.31(1.12–1.53) | 0.0009 |
Other | 1.22(1.11–1.35) | < 0.0001 | 1.85(1.58–2.18) | < 0.0001 |
Treatment Combination | | | | |
Treatment for both (ref.) | 1 | - | 1 | - |
Treatment for breast cancer only | 0.99(0.93–1.06) | 0.7528 | 0.93(0.85–1.01) | 0.092 |
Treatment for brain metastasis only | 2.42(2.21–2.65) | < 0.0001 | 2.30(2.00-2.63) | < 0.0001 |
No treatment for both | 3.14(2.91–3.38) | < 0.0001 | 2.65(2.36–2.98) | < 0.0001 |
The model included fourteen explanatory variables (age, race, ethnicity, insurance status, median household income quartile 2012–2016, percent of no |
high school degree, Charlson Deyo Score, histology, grade, breast cancer subtype, metastasis location sites, treatment combinations, and year of diagnosis). |
*Univariate logistic regressions ran first. Sex, tumor size, and lympho-vascular invasion all not significant so not included in multivariate model. |
Histology (p = 0.1024) was eliminated by backward elimination model set at 0.1 cutoff. |