Background
Methods
Design
Objectives
Patients
Clinical, biological and radiological data
Analysis of serum biomarkers
Statistical analysis
Ethical considerations
Results
Patients’ characteristics
Serum CA 15–3, CEA, tau, HER2 ECD and MMP-9
(A) | ||||
Total (n = 244) | BM (n = 86) | No BM (n = 158) | P-value | |
CEA (ng/mL) Median (range) Mean (SD) | (n = 226) 4.0 (1.0–5122.0) 62.02 (358.1) | (n = 81) 9.0 (1.0–5122.0) 122.72 (582.7) | (n = 145) 3.0 (1.0–768.0) 28.12 (92.1) | 0.025 |
CA 15–3 (U/mL) Median (range) Mean (SD) | (n = 226) 37.5 (8.0–1988.0) 177.27 (337.6) | (n = 81) 48.0 (11.0–1549.0) 210.92 (324.8) | (n = 145) 34.0 (8.0–1988.0) 158.48 (344.3) | 0.157 |
T-Tau (pg/mL) Median (range) Mean (SD) | (n = 244) 1.24 (0.0–755.5) 18.70 (92.2) | (n = 86) 1.56 (0.0–751.1) 30.60 (120.4) | (n = 158) 1.16 (0.0–755.5) 12.22 (72.1) | 0.232 |
HER2-ECD (ng/mL) Median (range) Mean (SD) | (n = 244) 14.00 (2.8–280) 36.87 (58.10) | (n = 86) 21.30 (2.8–280) 49.01 (68.20) | (n = 158) 12.15 (5.7–280) 30.26 (50.90) | 0.077 |
MMP-9 (ng/mL) Median (range) Mean (SD) | (n = 244) 333.80 (38.7–2051) 415.43 (300.70) | (n = 86) 416.08 (38.7–1575.8) 463.83 (292.2) | (n = 158) 317.00 (39–2051) 389.08 (302.8) | 0.066 |
(B) | ||||
Hazard-ratio | 95%CI | P-value | ||
CEA | 2.71 | 1.10–6.68 | 0.030 | |
CA 15–3 | 0.33 | 0.14–0.78 | 0.012 | |
T-Tau | 3.98 | 1.11–14.30 | 0.034 | |
HER2 ECD | 7.26 | 2.32–22.71 | 0.001 | |
MMP-9 | 4.69 | 2.05–10.73 | < 0.001 |
Prognostic factors
Whole MBC population (n = 244) | BM population (n = 86) | |||
---|---|---|---|---|
Parameter | Median OS in months (95 CI%) | P-value | Median OS in months (95 CI%) | P-value |
Initial characteristics | ||||
Tumor biology group
HER2+ HR+ HER2+ HR- HER2- HR+ Triple negative | 28.6 (16.5 – NC) 31.6 (20.2–34.5) 12.4 (10.4–22.5) 6.3 (4.5–10.4) | < 0.001 | 14.4 (8.1–20.1) 8.7 (2.6–20.2) 9.7 (2.6–16.2) 4.6 (2.0–8.5) | 0.0598 |
PR status
Negative Positive | 12.5 (10.6–17.8) 21.7 (16.2–35.6) | 0.044 | 8.1 (4.6–10.4) 16.2 (9.7–21.7) | 0.119 |
HER2 status
Negative Positive | 10.4 (8.4–12.4) 28.7 (20.1–33.9) | < 0.001 | 6.4 (4.2–10.0) 12.1 (8.1–19.1) | 0.037 |
Histological grade (SBR)
1 or 2 3 | 20.9 (15.1–31.6) 11.1 (9.5–15.0) | 0.012 | 10.4 (6.4–20.6) 8.1 (4.2–10.4) | 0.117 |
Metastatic status at BC diagnosis
M0 M1 | 13.6 (10.5–16.5) 27.2 (13.7–32.1) | 0.016 | 8.5 (4.7–10.0) 11.6 (4.2–20.9) | 0.056 |
Adjuvant or néoadjuvant CT
No Yes | 20.7 (16.8–31.6) 12.5 (10.3–15.5) | 0.009 | 11.6 (8.4–20.3) 6.8 (3.3–10.3) | 0.007 |
Characteristics at the time of the serum sample | ||||
ECOG status
Score 0 Score 1 Score 2 Score 3 | 34.5 (20.9–63.6) 16.5 (12.1–22.5) 6.8 (3.8–16.8) 2.0 (1.4–2.6) | < 0.001 | 14.4 (10.0 – NC) 12.1 (8.4–19.1) 8.5 (1.5–17.6) 2.0 (1.2–4.6) | < 0.001 |
Number of lines of CT
0 line 1 or 2 line(s) > 2 lines | 17.8 (15.0–27.8) 20.9 (16.3–32.0) 6.4 (4.6–10.4) | < 0.001 | 8.5 (4.7–17.6) 12.4 (8.4–20.3) 4.6 (2.2–9.7) | 0.007 |
Number of metastatic sites
1–3 ≥4 | 30.7 (19.1–59.2) 11.7 (9.9–15.0) | < 0.001 | 10.3 (5.6–19.1) 9.7 (4.7–12.1) | 0.309 |
Location of metastatic sites
Bone and/or subcutaneous only Visceral | 63.6 (16.5 – NC) 14.4 (11.4–19.1) | 0.0016 | NC 9.7 (5.6–10.8) | 0.843 |
Brain metastases
Absent Present | 30.4 (16.8–34.5) 9.7 (5.6–10.8) | < 0.001 | - - | – |
Liver metastases
Absent Present | 28.7 (14.9–36.8) 12.4 (10.6–17.2) | < 0.001 | 6.8 (3.8–10.4) 9.8 (4.9–13.6) | 0.377 |
Subcutaneous metastases
Absent Present | 19.2 (13.7–22.6) 10.4 (4.6–15.2) | 0.0034 | 10.0 (8.1–13.6) 4.7 (1.4–9.8) | 0.011 |
Metastases of other sites
Absent Present | 20.9 (16.2–30.7) 10.6 (6.4–12.5) | < 0.001 | 10.0 (8.1–15.5) 5.3 (2.8–11.6) | 0.876 |
Serum albumin level
Normal Low | 14.4 (11.1–19.4) 1.6 (1.1–2.4) | < 0.001 | 10.0 (6.8–12.4) 1.4 (0.7–2.6) | < 0.001 |
Serum CEA
Normal Elevated | 20.1 (15.5–28.6) 11.1 (8.7–13.6) | 0.003 | 10.0 (4.7–15.5) 9.7 (3.3–12.1) | 0.483 |
Serum CA 15–3
Normal Elevated | 28.7 (19.4–59.2) 11.4 (9.7–14.4) | < 0.001 | 10.4 (6.8–20.1) 8.5 (4.0–10.4) | 0.096 |
Serum HER2 ECD (cut-off 15 ng/mL)
Normal Elevated | 21.7 (15.2–31.6 11.4 (8.9–14.4) | < 0.001 | 10.3 (4.7–21.7) 8.7 (4.6–12.1) | 0.085 |
Serum Tau (cut-off 0.74 pg/mL*)
Normal Elevated | 33.2 (19.2–42.8) 12.4 (10.6–16.3) | 0.007 | 12.1 (6.8–28.6) 8.5 (4.6–10.4) | 0.060 |
Serum Tau (cut-off 1.24 pg/mL**)
Normal Elevated | 23.0 (15.0–33.2) 11.3 (9.5–16.3) | 0.0011 | 10.3 (4.6–12.4) 8.7 (4.9–12.4) | 0.942 |
Serum Tau (cut-off 3.17 pg/mL***)
Normal Elevated | 20.6 (16.2–30.4) 9.5 (4.9–10.8) | < 0.001 | 10.3 (5.3–13.6) 8.7 (2.6–10.8) | 0.389 |
Whole MBC population (n = 244) | BM population (n = 86) | |||||
---|---|---|---|---|---|---|
Parameter | Hazard-ratio | 95% CI | P-value | Hazard-ratio | 95% CI | P-value |
Performance status | ||||||
ECOG 0 | 1 | 1 | ||||
ECOG 1 | 1.90 | 1.17–3.07 | 0.009 | 1.58 | 0.65–3.85 | 0.316 |
ECOG 2 | 2.66 | 1.44–4.90 | 0.002 | 1.63 | 0.54–4.96 | 0.385 |
ECOG 3 | 11.82 | 5.98–23.36 | < 0.001 | 11.16 | 3.50–35.63 | < 0.001 |
Tumor biology | ||||||
HER2+ / HR+ | 1 | 1 | ||||
HER2+ / HR- | 0.97 | 0.56–1.66 | 0.910 | 1.41 | 0.67–2.96 | 0.360 |
HER2- / HR+ | 1.72 | 1.09–2.71 | 0.020 | 2.30 | 1.16–4.56 | 0.017 |
Triple negative | 6.50 | 3.63–11.63 | < 0.001 | 2.54 | 1.00–6.47 | 0.050 |
Patient’s age | ||||||
< 50 | 1 | 1 | ||||
50–70 | 1.67 | 1.08–2.59 | 0.022 | 2.00 | 1.15–3.45 | 0.013 |
≥71 | 1.85 | 0.94–3.64 | 0.077 | 2.06 | 0.90–4.72 | 0.088 |
Number of previous metastatic CT lines | ||||||
0 | 1 | – | ||||
1 or 2 | 1.53 | 0.95–2.47 | 0.080 | |||
> 2 | 2.50 | 1.52–4.12 | < 0.001 | |||
Adjuvant or neoadjuvant CT | – | 1.44 | 0.88–2.38 | 0.148 | ||
Brain metastases | 2.03 | 1.39–2.97 | < 0.001 | – | ||
Neurological deficit associated with BM | – | 2.75 | 1.50–5.03 | < 0.001 | ||
Subcutaneous metastases | 1.85 | 1.26–2.72 | 0.002 | 2.87 | 1.64–5.04 | < 0.001 |
Elevated HER2 ECD (cut-off 15 ng/mL) | 1.88 | 1.21–2.91 | 0.005 | 2.24 | 1.13–4.43 | 0.007 |
Elevated Tau (cut-offs 1.24 and 0.74 pg/mL, respectively) | 1.58 | 1.09–2.31 | 0.017 | 2.43 | 1.16–5.09 | 0.018 |