Table 5.
Hazard ratios (HRs) of breast cancer-specific mortality among women with primary breast cancer as the second malignancy (BCa-2), stratified clinical characteristics, compared to women with primary breast cancer as the first malignancy (BCa-1): a SEER population-based study in US, 1990–2015
| BCa-1 N (IR) |
BCa-2 N (IR) |
HR (95% CI)a | |
|---|---|---|---|
| Age at diagnosis, years | |||
| 18–44 | 19,010 (2.0) | 164 (2.0) | 1.05 (0.90–1.22) |
| 45–54 | 25,197 (1.6) | 385 (1.7) | 1.05 (0.95–1.16) |
| 55–64 | 25,246 (1.6) | 720 (1.7) | 1.19 (1.11–1.28) |
| 65–74 | 20,535 (1.7) | 978 (1.8) | 1.15 (1.08–1.23) |
| 75–84 | 16,797 (2.5) | 1060 (2.5) | 1.10 (1.04–1.17) |
| ≥ 85 | 8179 (6.0) | 522 (5.0) | 1.01 (0.93–1.11) |
| P for interaction | 0.056 | ||
| Year of diagnosis | |||
| 1990–1993 | 11,532 (1.8) | 344 (2.2) | 1.07 (0.96–1.19) |
| 1994–1997 | 13,760 (1.8) | 393 (1.9) | 0.98 (0.89–1.09) |
| 1998–2001 | 21,259 (1.7) | 516 (1.9) | 1.15 (1.05–1.25) |
| 2002–2005 | 26,642 (1.8) | 740 (2.0) | 1.15 (1.06–1.23) |
| 2006–2009 | 23,333 (2.0) | 890 (2.1) | 1.13 (1.06–1.21) |
| 2010–2015 | 18,438 (2.4) | 946 (2.6) | 1.14 (1.07–1.22) |
| P for interaction | 0.136 | ||
| Histology | |||
| Ductal | 79,321 (1.8) | 2521 (2.0) | 1.13 (1.09–1.18) |
| Lobular | 9222 (1.9) | 393 (2.4) | 1.06 (0.95–1.17) |
| Mixed | 8133 (1.4) | 314 (1.8) | 1.20 (1.08–1.35) |
| Others | 18,288 (3.2) | 601 (3.5) | 1.03 (0.95–1.12) |
| P for interaction | 0.067 | ||
| Tumor grade | |||
| Well differentiated | 5445 (0.5) | 294 (0.7) | 1.43 (1.27–1.61) |
| Moderately differentiated | 31,639 (1.4) | 1149 (1.6) | 1.15 (1.09–1.22) |
| Poorly differentiated | 53,944 (3.0) | 1593 (3.6) | 1.18 (1.12–1.24) |
| Undifferentiated | 2400 (2.9) | 52 (3.1) | 1.07 (0.82–1.41) |
| P for interaction | 0.011 | ||
| Tumor size | |||
| 0–2 cm | 28,594 (0.7) | 1264 (1.0) | 1.29 (1.22–1.36) |
| 2–5 cm | 45,123 (2.7) | 1434 (3.5) | 1.15 (1.09–1.21) |
| > 5 cm | 23,418 (7.4) | 563 (8.6) | 1.25 (1.15–1.36) |
| P for interaction | 0.011 | ||
| Tumor stage | |||
| Local | 27,833 (0.7) | 1293 (1.0) | 1.31 (1.24–1.39) |
| Regional | 48,765 (2.7) | 1398 (3.3) | 1.07 (1.01–1.13) |
| Distant | 33,806 (21.2) | 981 (26.1) | 1.03 (0.97–1.10) |
| P for interaction | < 0.001 | ||
| Molecular subtypesb | |||
| HR+/HER2- | 8076 (1.5) | 447 (1.7) | 1.09 (0.99–1.20) |
| HR+/HER2+ | 1743 (2.3) | 75 (2.6) | 1.38 (1.09–1.74) |
| HR−/HER2+ | 1281 (3.9) | 62 (5.5) | 1.61 (1.25–2.08) |
| Triple negative | 4322 (5.5) | 213 (6.7) | 1.18 (1.03–1.36) |
| P for interaction | 0.020 | ||
| Treatment modesc | |||
| Lumpectomy only | 5816 (1.2) | 349 (1.7) | 1.32 (1.19–1.47) |
| Mastectomy only | 11,190 (1.3) | 510 (1.6) | 1.13 (1.03–1.23) |
| Chemo−/radio-therapy | 12,602 (16.5) | 365 (17.9) | 1.14 (1.03–1.27) |
| Lumpectomy plus chemo/radio-therapy | 17,627 (0.8) | 555 (0.9) | 1.13 (1.03–1.23) |
| Mastectomy plus chemo/radio-therapy | 28,121 (2.8) | 649 (3.3) | 1.13 (1.04–1.22) |
| Othersd | 14,316 (13.9) | 664 (14.1) | 0.99 (0.92–1.07) |
| P for interaction | 0.002 | ||
NOTE. Patients with missing information on tumor stage (N = 14,459, 1.57%), tumor grade (N = 97,126, 10.56%) or size (N = 52,267, 5.68%) or molecular types (N = 24,220, 7.6%) were not included for the corresponding analysis. We added an interaction term between BCa-2 and the risk modifier and reported the statistical significance of the term as P for interaction
Abbreviations: CI Confidence interval, HR+ Hormone-receptor positive, HR- Hormone-receptor negative, HER2 Human epidermal growth factor receptor 2, HR Hazard ratio, IR Mortality rate per 100 person-years, N Number of deaths
a HR was adjusted for age (continuous) and calendar period at diagnosis, race, cohabitation status, percentile of cost of living and high-school education in county of residence, tumor stage, histology, tumor grade, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status, surgery, radio-therapy, and chemo-therapy
b Information on HER2 status was available from 2010 onward, and thus the analysis was restricted to patients diagnosed thereafter
c Information on surgery was available from 1998 onward, and thus the analysis was restricted to patients diagnosed thereafter
d Others included surgery (no/unknown), chemotherapy (no/unknown), and radiotherapy (no/unknown)