Background
Methods
Patients and study design
CTC enumeration
HER2 status
Data analysis and statistics
Results
Patients and study design
CTC status and response
All patients, BL | CTCBL+ |
P
| All patients, 1C | CTC1C+ |
P
| |
---|---|---|---|---|---|---|
Patients | 393 | 133 (34%)* | 201 | 57 (28%) | ||
Age, median (range); years | ||||||
at initial diagnosis | 51 (23–81) | 50 (28–81) | 0.853 | 50 (28–77) | 50 (33–77) | 0.570 |
at study inclusion | 59 (29–89) | 57 (33–81) |
0.030
| 57 (33–89) | 55 (33–77) | 0.092 |
Baseline CTC count, median (range); number/7.5 ml blood | 1 (0–930) | 21 (5–930) | — | — | ||
ER status | 0.631 | 0.729 | ||||
ER+ | 271 | 94 (35%) | 136 | 41 (30%) | ||
ER- | 107 | 34 (32%) | 55 | 15 (27%) | ||
No data | 15 | 5 (33%) | 10 | 1 (10%) | ||
PgR Status | 0.819 | 0.866 | ||||
PgR+ | 240 | 81 (34%) | 124 | 36 (29%) | ||
PgR- | 130 | 46 (35%) | 64 | 20 (31%) | ||
No data | 23 | 6 (26%) | 13 | 1 (8%) | ||
HER2 status of primary tumor | 0.119 |
0.028
| ||||
HER2+ | 67 | 18 (27%) | 30 | 4 (13%) | ||
HER2- | 274 | 102 (37%) | 142 | 49 (35%) | ||
No data | 52 | 13 (25%) | 29 | 4 (14%) | ||
Molecular subtypes | 0.221 | 0.062 | ||||
HR+/HER2- | 216 | 83 (38%) | 110 | 39 (35%) | ||
HER2+ | 67 | 18 (27%) | 30 | 4 (13%) | ||
TNBC | 57 | 19 (33%) | 32 | 10 (31%) | ||
No data | 53 | 13 (25%) | 29 | 4 (14%) | ||
Metastasis site |
< 0.001
|
0.005
| ||||
Bone | 68 | 25 (37%) | 40 | 16 (40%) | ||
Visceral/local | 134 | 28 (21%) | 68 | 10 (15%) | ||
Both | 191 | 80 (42%) | 93 | 31 (33%) | ||
No data | 0 | 0 (0%) | 0 | 0 (0%) | ||
Number of metastasis sites | 0.372 | 1.000 | ||||
1 | 88 | 26 (30%) | 48 | 14 (29%) | ||
≥ 2 | 305 | 107 (35%) | 153 | 43 (28%) | ||
No data | 0 | 0 (0%) | 0 | 0 (0%) | ||
Line of therapy | 0.724 | 0.097 | ||||
1 | 175 | 62 (35%) | 97 | 26 (27%) | ||
2 | 81 | 28 (35%) | 44 | 8 (18%) | ||
≥ 3 | 135 | 42 (31%) | 59 | 22 (37%) | ||
No data | 2 | 1 (50%) | 1 | 1 (100%) | ||
Treatments before study | ||||||
Hormonal therapy | 0.904 | 0.167 | ||||
Yes | 289 | 97 (34%) | 143 | 45 (31%) | ||
No | 104 | 36 (35%) | 58 | 12 (21%) | ||
No data | 0 | 0 (0%) | 0 | 0 (0%) | ||
Antibody therapy (bevacizumab or other) | 0.210 |
0.023
| ||||
Yes | 103 | 47 (46%) | 54 | 22 (41%) | ||
No | 288 | 86 (30%) | 146 | 35 (24%) | ||
No data | 2 | 0 (0%) | 1 | 0 (0%) | ||
Anti HER2 therapy (trastuzumab, lapatinib) |
0.012
|
0.027
| ||||
Yes | 81 | 18 (22%) | 37 | 5 (14%) | ||
No | 311 | 115 (37%) | 163 | 52 (32%) | ||
No data | 1 | 0 (0%) | 1 | 0 (0%) | ||
Chemotherapy |
0.022
| 0.054 | ||||
Mono-CHT | 87 | 24 28%) | 39 | 8 (21%) | ||
Poly-CHT | 109 | 35 (32%) | 64 | 18 (28%) | ||
Bevacizumab + CHT | 93 | 44 (49%) | 47 | 21 (45%) | ||
Other CHTs | 41 | 9 (22%) | 22 | 3 (14%) | ||
No CHT | 62 | 21 (34%) | 28 | 7 (25%) | ||
No data | 1 | 0 (0%) | 1 | 0 (0%) | ||
Radiological response after first cycle of chemotherapy | 0.104 |
0.011
| ||||
CR/PR/SD | 162 | 52 (32%) | 99 | 23 (23%) | ||
PD | 93 | 40 (43%) | 55 | 24 (44%) | ||
No data | 138 | 41 (30%) | 47 | 10 (21%) |
CTC status and survival
CTCBL(baseline) | CTC1C(after 1st cycle) | PFS (months) | OS (months) | Progression | ||
---|---|---|---|---|---|---|
Median [95% CI] | Median [95% CI] | Numbers (percentage) | ||||
Favorable
|
Negative
(CTC
BL
-)
|
Negative
(CTC
1C
-)
| 8.7 [6.6–11.5] | 30.6 [27.4–na] | 20/75 (27%) | |
Positive
(CTC
BL
+)
|
Negative
(CTC
1C
-)
| 8.0 [5.5–12.1] | 16.7 [13.6–na] | 11/32 (34%) | ||
Unfavorable
|
Positive
(CTC
BL
+)
|
Positive
(CTC
1C
+)
| 4.3 [3.6–6.1] | 7.7 [6.1–13.1] | 21/41 (51%) | |
Negative
(CTC
BL
-)
|
Positive
(CTC
1C
+)
| 3.7 [2.5–na] | 14.0 [5.7–na] | 3/6 (50%) |
Response and survival
Multivariate regression analysis
PFS | OS | |||||
---|---|---|---|---|---|---|
Hazard ratio | 95% CI |
P
| Hazard ratio | 95% CI |
P
| |
Baseline CTC status (CTC
BL
)
| ||||||
< 5 CTC (CTCBL-) | 1.00 | 1.00 | ||||
≥ 5 CTC (CTCBL+) | 1.55 | 1.19–2.01 |
0.001
| 2.79 | 2.04–5.63 |
< 0.001
|
Age at inclusion
| ||||||
Per year | 0.99 | 0.98–1.00 | 0.207 | 1.00 | 0.99–1.01 | 0.938 |
Number of metastatic sites
| ||||||
One site | 1.00 | 1.00 | ||||
Multiple sites | 0.97 | 0.66–1.43 | 0.892 | 0.71 | 0.41–1.23 | 0.227 |
Site of metastasis
| ||||||
Bone | 1.00 | 1.00 | ||||
Visceral/local | 0.98 | 0.67–1.46 | 0.939 | 1.75 | 1.00–3.01 | 0.052 |
Both | 1.07 | 0.71–1.63 | 0.739 | 2.55 | 1.41–4.60 |
0.002
|
Line of therapy
| ||||||
1 | 1.00 | 1.00 | ||||
2 | 1.35 | 0.93–1.95 | 0.113 | 1.45 | 0.92–2.28 | 0.112 |
≥ 3 | 1.91 | 1.40–2.59 |
< 0.001
| 2.01 | 1.37–2.96 |
< 0.001
|
Molecular Subtypes
| ||||||
HR+/HER2- | 1.00 | ° | 1.00 | |||
HER2+ | 1.10 | 0.79–1.52 | 0.577 | 1.09 | 0.72–1.63 | 0.695 |
TNBC | 1.92 | 1.36–2.71 |
< 0.001
| 2.86 | 1.91–4.27 |
< 0.001
|
PFS | OS | |||||
---|---|---|---|---|---|---|
Hazard ratio | 95% CI |
P
| Hazard ratio | 95% CI |
P
| |
CTC
KIN
| ||||||
CTCBL- to CTC1C- | 1.00 | 1.00 | ||||
CTCBL+ to CTC1C- | 1.01 | 0.62–1.64 | 0.981 | 1.68 | 0.85–3.32 | 0.135 |
CTCBL+ to CTC1C+ | 2.17 | 1.39–3.37 |
< 0.001
| 5.58 | 3.06–10.15 |
< 0.001
|
CTCBL- to CTC1C+ | 2.17 | 0.91–5.14 | 0.079 | 2.56 | 0.76–8.00 | 0.134 |
Age at inclusion
| ||||||
Per year | 0.99 | 0.98–1.00 | 0.333 | 0.99 | 0.97–1.01 | 0.284 |
Number of metastatic sites
| ||||||
One site | 1.00 | 1.00 | ||||
Multiple sites | 0.94 | 0.98–1.01 | 0.832 | 0.59 | 0.24–1.48 | 0.260 |
Site of metastasis
| ||||||
Bone | 1.00 | 1.00 | ||||
Visceral/local | 1.10 | 0.59–2.04 | 0.768 | 2.12 | 0.82–5.49 | 0.124 |
Both | 1.27 | 0.68–2.37 | 0.449 | 3.35 | 1.27–8.82 |
0.014
|
Line of therapy
| ||||||
1 | 1.00 | 1.00 | ||||
2 | 1.66 | 1.00–2.75 |
0.049
| 2.01 | 1.02–3.99 |
0.045
|
≥ 3 | 2.49 | 1.58–3.94 |
< 0.001
| 2.49 | 1.32–4.65 |
0.004
|
Molecular Subtypes
| ||||||
HR+/HER2- | 1.00 | 1.00 | ||||
HER2+ | 1.34 | 0.81–2.19 | 0.252 | 1.37 | 0.64–2.91 | 0.418 |
TNBC | 2.58 | 1.53–4.35 |
< 0.001
| 3.92 | 2.11–7.30 |
< 0.001
|