Article Figures & Data
Figures
- Figure 1.
BCI risk groups for prediction of early- and late-distant recurrence in the Stockholm TAM cohort (ER+, LN−) and the multi-institutional cohort (ER+ LN−). A and C, early-distant recurrence (0–5 years). B and D, late-distant recurrence (>5 years) in patients recurrence-free at 5 years. HRs compare intermediate-risk (top) and high-risk (bottom) versus low-risk groups, respectively.
- Figure 2.
Continuous BCI score for early (0–5 years) and late (>5 years) rate of distant recurrence in the Stockholm TAM cohort (ER+ LN−). A, rate of early-distant recurrence at 5 years. B, rate of late-distant recurrence at 10 years in patients recurrence-free at 5 years. Gray and black rugged bars indicate individual patient BCI scores for nonrecurrence and recurrence respectively.
Tables
- Table 1.
Patient clinicopathologic characteristics in Stockholm and multi-institutional cohorts
Stockholm untreated (n = 283) Stockholm TAM-treated (n = 317) Multi-institutional (n = 358) Age at surgery, y <50 4 (1%) 2 (<1%) 108 (30%) 50–59 92 (33%) 89 (28%) 113 (32%) 60–69 178 (63%) 214 (68%) 93 (26%) ≥70 9 (3%) 12 (4%) 44 (12%) Tumor size ≤20 mm 230 (81%) 259 (82%) 237 (66%) >20 mm 51 (18%) 55 (17%) 121 (34%) Unknown 2 (1%) 3 (1%) 0 Tumor grade Well 69 (24%) 67 (21%) 82 (23%) Moderate 175 (62%) 211 (67%) 219 (61%) Poor 39 (14%) 39 (12%) 57 (16%) PR status Negative 73 (26%) 72 (23%) NA Positive 182 (64%) 220 (69%) Unknown 28 (10%) 25 (8%) HER2 status Negative 257 (91%) 295 (93%) 316 (88%) Positive 26 (9%) 22 (7%) 42 (12%) Adjuvant chemotherapy No 283 (100%) 317 (100%) 243 (68%) Yes 0 0 115 (32%) Distant recurrence Overall 56 (100%) 33 (100%) 57 (100%) Early (≤5 y) 27 (48%) 13 (39%) 34 (60%) Late (>5 y) 29 (52%) 20 (61%) 23 (40%) BCI groups Low 156 (55%) 202 (64%) 196 (55%) Intermediate 75 (27%) 65 (20%) 78 (22%) High 52 (18%) 50 (16%) 84 (23%) Abbreviation: NA, not available.
- Table 2.
Kaplan–Meier estimates of early- and late-distant recurrence-free survival for 3 BCI risk groups in Stockholm TAM and multi-institutional cohorts
Stockholm TAM-treated Multi-institutional Patient subgroups No. of patients (%) No. DR DRFS (95% CI) No. of patients (%) No. DR DRFS (95% CI) Early-distant recurrence at 5 y BCI low risk 202 (64%) 4 98.0 (96.0–100) 196 (55%) 8 95.9 (93.1–98.7) BCI intermediate risk 65 (20%) 3 95.2 (90.1–100) 78 (22%) 6 92.3 (86.5–98.4) BCI high risk 50 (16%) 6 87.8 (79.0–97.4) 84 (23%) 20 75.5 (66.7–85.4) Late-distant recurrence at 10 ya BCI low risk 184 (65%) 8 97.2 (94.8–99.7) 181 (58%) 4 97.5 (95.0–100.0) BCI intermediate risk 58 (20%) 5 92.8 (86.2–99.9) 70 (22%) 10 83.1 (73.8–93.5) BCI high risk 43 (15%) 7 89.9 (80.9–99.8) 61 (20%) 9 85.0 (76.4–94.5) Abbreviations: DR, distant recurrence; DRFS, distant recurrence-free survival.
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↵aIn patients who were recurrence-free at 5 years.
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- Table 3.
Early-distant recurrence: univariate and multivariate Cox model analysis after stepwise variable selection by AIC of likelihood of early-distant recurrence in Stockholm TAM and multi-institutional cohorts for all (ER+) and ER+/HER2− only patients
All patients (ER+) ER+/HER2− only Variablea HR (95% CI) P HR (95% CI) P Stockholm TAM n = 317 (13 DR) n = 295 (11 DR) Univariate analysis Age at surgery 0.76 (0.26–2.20) 0.62 0.59 (0.19–1.86) 0.37 Tumor size 1.68 (0.46–6.21) 0.44 2.44 (0.63–9.45) 0.20 Tumor grade 1.28 (0.28–5.84) 0.75 1.08 (0.23–5.08) 0.92 PR status 1.03 (0.28–3.79) 0.97 0.69 (0.18–2.66) 0.59 HER2 status 2.56 (0.56–11.68) 0.23 NA NA BCI 9.08 (1.86–44.4) 0.006 16.25 (2.59–102.0) 0.003 Multivariate analysis BCI 9.08 (1.86–44.4) 0.006 16.25 (2.59–102.0) 0.003 Multi-institutional n = 358 (34 DR) n = 316 (26 DR) Univariate analysis Age at surgery 1.10 (0.80–1.50) 0.57 1.16 (0.81–1.65) 0.42 Tumor size 1.77 (0.90–3.47) 0.10 1.49 (0.68–3.24) 0.32 Tumor grade 3.21 (0.98–10.51) 0.05 2.55 (0.77–8.49) 0.13 HER2 status 2.44 (1.10–5.39) 0.03 NA NA Chemo 0.99 (0.48–2.04) 0.98 1.08 (0.49–2.48) 0.86 BCI 11.92 (4.53–31.33) <0.0001 13.71 (4.54–41.36) <0.0001 Multivariate analysis Tumor grade 2.32 (0.71–7.58) 0.17 NA NA BCI 11.50 (4.22–31.32) <0.0001 13.71 (4.54–41.36) <0.0001 Abbreviations: AIC, Akaike's Information Criterion; DR, distant recurrences; NA, not applicable.
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↵aAge was by 10 years increment; tumor size was greater than 2 cm versus 2 cm or less; tumor grade was moderate/poorly differentiated versus well differentiated; PR and HER2 status was positive versus negative; chemo was no versus yes; BCI was continuous variable with 5 units increment (chosen to dichotomize BCI to facilitate the comparison of HRs with clinical covariates).
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- Table 4.
Late-distant recurrence: univariate and multivariate Cox model analysis after stepwise variable selection by AIC of likelihood of late-distant recurrence in Stockholm TAM and multi-institutional cohorts for all (ER+) and ER+/HER2− patients
All patients (ER+) ER+/HER2− Only Variablea HR (95% CI) P HR (95% CI) P Stockholm TAM n = 285 (20 DR) n = 266 (18 DR) Univariate analysis Age at surgery 0.59 (0.26–1.34) 0.21 0.54 (0.23–1.29) 0.17 Tumor size 1.52 (0.50–4.57) 0.46 1.43 (0.41–4.99) 0.57 Tumor grade 0.69 (0.27–1.70) 0.41 0.87 (0.32–2.35) 0.78 PR status 0.45 (0.18–1.11) 0.08 0.50 (0.18–1.34) 0.17 HER2 status 1.38 (0.32–5.98) 0.67 NA NA BCI 4.07 (1.26–13.10) 0.019 4.92 (1.36–17.78) 0.015 Multivariate analysis PR status 0.52 (0.21–1.32) 0.17 0.54 (0.20–1.46) 0.22 BCI 3.50 (1.09–11.21) 0.035 4.57 (1.28–16.37) 0.020 Multi-Institutional n = 312 (23 DR) n = 281 (22 DR) Univariate analysis Age at surgery 1.32 (0.90–1.95) 0.16 1.48 (1.00–2.20) 0.05 Tumor size 3.37 (1.46–7.79) 0.01 3.17 (1.35–7.41) 0.01 Tumor grade 2.37 (0.88–6.38) 0.09 2.91 (0.98–8.58) 0.05 HER2 status 0.40 (0.05–2.98) 0.37 NA NA Chemo 0.89 (0.38–2.11) 0.80 1.04 (0.42–2.54) 0.94 BCI 8.01 (2.61–24.56) 0.0003 11.03 (3.36–36.21) <0.0001 Multivariate analysis Tumor size 2.66 (1.14–6.20) 0.02 2.53 (1.07–5.97) 0.03 HER2 status 0.17 (0.02–1.32) 0.09 NA NA BCI 9.24 (2.85–30.00) 0.0002 9.33 (2.83–30.76) 0.0002 Abbreviations: DR, distant recurrences; NA, not applicable.
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↵aAge was by 10 years increment; tumor size was greater than 2 cm versus 2 cm or less; tumor grade was poorly differentiated versus moderate/well differentiated; PR and HER2 status was positive versus negative; chemo was no versus yes; BCI was continuous variable with 5 units increment (chosen to dichotomize BCI to facilitate the comparison of HRs with clinical covariates).
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Files in this Data Supplement:
- Supplementary Figures 1-7 - Supplementary Figures 1-7 - PDF file 117K, Supplementary Figure 1. Cohorts used for BCI model training and validation Supplementary Figure 2. Performance of H:I and MGI for early (0-5 years) and late (> 5 years) distant recurrence in Stockholm ER+, LN- untreated patients. A, C: H:I, 0-5 years and > 5 years. B, D: MGI, 0-5 years and > 5 years. Supplementary Figure 3. BCI risk groups for prediction of overall distant recurrence in Stockholm TAM and Multi-institutional cohorts, ER+, LN- patients. Supplementary Figure 4. Continuous BCI score for overall (0 - 10 years) rate of distant recurrence in Stockholm TAM cohort. Supplementary Figure 5. BCI risk groups for prediction of early and late distant recurrence in the combined StockholmTAM and Multi-institutional cohort; ER+, LN-, tamoxifen-treated patients. Supplementary Figure 6. Continuous BCI score for early (0 - 5 years) and late (> 5 years) rate of distant recurrence in the combined Stockholm TAM and Multi-institutional cohort (ER+, LN-, tamoxifen-treated patients). Supplementary Figure 7. Prediction of tamoxifen benefit by H/I. A: no benefit of tamoxifen in H/I-low patients. B: benefit of tamoxifen in H/I-high patients
- Supplementary Tables 1-2 - Supplementary Tables 1-2 - PDF file 101K, Supplementary Table 1. Kaplan-Meier estimates of overall distant recurrence free survival (DRFS) for 3 BCI risk groups in Stockholm TAM-treated and Multi-institutional cohorts. Supplementary Table 2. Overall distant recurrence: Univariate and multivariate Cox model analysis after stepwise variable selection by AIC of likelihood of overall distant recurrence in Stockholm TAM and Multi-institutional cohorts for all ER+ and ER+, HER2- patients
Volume 19, Issue 15
