Introduction
Methods
Study design
Tumor material
Statistical analysis
Results
Population characteristics
<35 years | 35–39 years | 40–49 years | 50–69 years | |||||
---|---|---|---|---|---|---|---|---|
n = 445 |
n = 190 |
n = 192 |
n = 293 | |||||
No. | (%) | No. | (%) | No. | (%) | No. | (%) | |
Year of diagnosis | ||||||||
1992–1997 | 169 | (38.0) | 82 | (43.2) | 86 | (44.8) | 89 | (30.4) |
1998–2002 | 175 | (39.3) | 61 | (32.1) | 62 | (32.3) | 132 | (45.1) |
2003–2005 | 101 | (22.7) | 47 | (24.7) | 44 | (22.9) | 72 | (24.6) |
Detection by screening | 6 | (1.3) | 5 | (2.6) | 45 | (23.4) | 167 | (57.0) |
Hereditya
| ||||||||
Any heredity | 187 | (42.0) | 73 | (38.4) | 59 | (30.7) | 80 | (27.3) |
≥1 first grade relative | 81 | (18.2) | 37 | (19.5) | 25 | (13.0) | 50 | (17.1) |
Tumor size | ||||||||
1–10 mm | 67 | (15.1) | 27 | (14.2) | 35 | (18.2) | 77 | (26.3) |
11–20 mm | 148 | (33.3) | 72 | (37.9) | 80 | (41.7) | 136 | (46.4) |
21–50 mm | 189 | (42.5) | 72 | (37.9) | 70 | (36.5) | 67 | (22.9) |
>51 mm | 38 | (8.5) | 16 | (8.4) | 6 | (3.1) | 11 | (3.8) |
Missing | 3 | (0.7) | 3 | (1.6) | 1 | (0.5) | 2 | (0.7) |
Lymph node status | ||||||||
Node neg | 227 | (51.0) | 90 | (47.4) | 116 | (60.4) | 214 | (73.0) |
1–3 nodes pos | 126 | (28.3) | 68 | (35.8) | 47 | (24.5) | 57 | (19.5) |
>4 nodes pos | 92 | (20.7) | 32 | (16.8) | 29 | (15.1) | 22 | (7.5) |
Stage | ||||||||
I | 14 | (32.4) | 63 | (33.2) | 87 | (45.3) | 172 | (58.7) |
IIa | 126 | (28.3) | 50 | (26.3) | 44 | (22.9) | 74 | (25.3) |
IIb | 71 | (16.0) | 35 | (18.4) | 28 | (14.6) | 21 | (7.2) |
III | 103 | (23.1) | 40 | (21.1) | 33 | (17.2) | 26 | (8.9) |
Unstaged | 1 | (0.2) | 2 | (1.1) | 0 | 0 | ||
Grade (Elston) | ||||||||
I | 21 | (5.3) | 21 | (12.7) | 31 | (17.9) | 75 | (27.3) |
II | 140 | (35.6) | 63 | (38.2) | 79 | (45.7) | 131 | (47.6) |
III | 232 | (59.0) | 81 | (49.1) | 63 | (36.4) | 69 | (25.1) |
Missing | 52 | 25 | 19 | 18 | ||||
Estrogen receptorb
| ||||||||
Pos | 208 | (47.2) | 122 | (64.9) | 146 | (77.7) | 225 | (78.1) |
Neg | 233 | (52.8) | 66 | (35.1) | 42 | (22.3) | 63 | (21.9) |
Missing | 4 | 2 | 4 | 5 | ||||
Progesterone receptorb
| ||||||||
Pos | 155 | (35.4) | 85 | (45.2) | 114 | (60.6) | 145 | (51.1) |
Neg | 283 | (64.6) | 103 | (54.8) | 74 | (39.4) | 139 | (48.9) |
Missing | 7 | 2 | 4 | 9 | ||||
Ki-67 (%) | ||||||||
Low ≤20 | 70 | (18.8) | 42 | (26.9) | 67 | (40.1) | 127 | (51.2) |
High >20 | 302 | (81.2) | 114 | (73.1) | 100 | (59.9) | 121 | (48.8) |
Missing | 73 | 34 | 25 | 45 | ||||
Her2 | ||||||||
Neg | 296 | (79.6) | 127 | (81.4) | 150 | (90.4) | 225 | (91.8) |
Pos | 76 | (20.4) | 29 | (18.6) | 16 | (9.6) | 20 | (8.2) |
Missing | 73 | 34 | 26 | 48 | ||||
Subtype | ||||||||
Luminal A | 27 | (7.7) | 23 | (15.1) | 40 | (25.8) | 59 | (25.9) |
Luminal B | 132 | (37.5) | 66 | (43.4) | 80 | (51.6) | 117 | (51.3) |
Luminal-Her2 | 35 | (9.9) | 16 | (10.5) | 7 | (4.5) | 10 | (4.4) |
Her2-positive | 40 | (11.4) | 13 | (8.6) | 8 | (5.2) | 9 | (3.9) |
Triple-negative | 118 | (33.5) | 34 | (22.4) | 20 | (12.9) | 33 | (14.5) |
Unclassified | 93 | 38 | 37 | 65 | ||||
Presence of: | ||||||||
LVIb
| 139 | (31.2) | 43 | (22.6) | 39 | (20.3) | 32 | (10.9) |
Invasive multifocality | 96 | (21.6) | 39 | (20.5) | 35 | (18.2) | 46 | (15.7) |
Extensive DCIS | 92 | (20.7) | 43 | (22.6) | 30 | (15.6) | 37 | (12.6) |
<35 years | 35–39 years | 40–49 years | 50–69 years | |||||
---|---|---|---|---|---|---|---|---|
n = 445 |
n = 190 |
n = 192 |
n = 293 | |||||
No. | (%) | No. | (%) | No. | (%) | No. | (%) | |
Breast surgery | ||||||||
BCS | 206 | (46.3) | 94 | (49.5) | 117 | (60.9) | 194 | (66.2) |
Mastectomy | 239 | (53.7) | 94 | (49.5) | 74 | (38.5) | 99 | (33.8) |
No surgery | 0 | 2 | (1.1) | 1 | (0.5) | 0 | ||
Chemotherapy | ||||||||
No | 109 | (24.5) | 48 | (25.3) | 103 | (53.6) | 204 | (69.6) |
Yes | 336 | (75.5) | 142 | (74.7) | 89 | (46.4) | 89 | (30.4) |
CMF | 78 | (23.2) | 45 | (31.7) | 27 | (30.3) | 24 | (27.0) |
FEC | 208 | (61.9) | 82 | (57.7) | 54 | (60.7) | 60 | (67.4) |
Taxanes | 47 | (14.0) | 15 | (10.6) | 6 | (6.7) | 5 | (5.6) |
Other | 3 | (0.9) | 0 | 2 | (2.2) | 0 | ||
Proportion neoadjuvant | 76 | (17.1) | 29 | (15.3) | 13 | (6.8) | 8 | (2.7) |
Chemotherapy when N+ | 214 | (98.2) | 95 | (95.0) | 72 | (94.7) | 61 | (77.2) |
Chemotherapy when hormone rec posa
| 169 | (67.6) | 85 | (65.9) | 65 | (41.7) | 59 | (25.0) |
Trastuzumab | ||||||||
Yes | 18 | (4.0) | 5 | (2.6) | 3 | (1.6) | 4 | (1.4) |
No | 427 | (96.0) | 185 | (97.4) | 189 | (98.4) | 289 | (98.6) |
Radiotherapy | ||||||||
Yes | 358 | (80.4) | 149 | (78.4) | 160 | (83.3) | 231 | (78.8) |
No | 87 | (19.6) | 41 | (21.6) | 32 | (16.7) | 62 | (21.2) |
Breast radiation when BCS | 196 | (95.1) | 92 | (97.9) | 113 | (96.6) | 187 | (96.4) |
Chest wall radiation when mastectomy | 162 | (67.8) | 57 | (60.6) | 46 | (62.2) | 43 | (43.4) |
Axillary radiation when N+ | 168 | (77.1) | 68 | (68.0) | 49 | (64.5) | 58 | (73.4) |
Endocrine therapy | ||||||||
Yes | 208 | (46.7) | 90 | (47.4) | 109 | (56.8) | 190 | (64.8) |
No | 237 | (53.3) | 100 | (52.6) | 82 | (42.7) | 102 | (34.8) |
Missing | 0 | 0 | 1 | (0.5) | 1 | (0.3) | ||
Endocrine therapyb when hormone rec posa
| 176 | (70.4) | 80 | (62.0) | 97 | (62.2) | 177 | (75.0) |
Ovarian suppression when hormone rec posa
| 79 | (31.9) | 28 | (22.0) | 17 | (11.1) | 4 | (1.7) |
Univariate analysis
<35 years | 35–39 years | 40–49 years | 50–69 years | ||||
---|---|---|---|---|---|---|---|
n = 445 |
n = 190 |
n = 192 |
n = 293 | ||||
Unadjusted |
2.75
|
(1.93–3.94)
|
2.33
|
(1.54–3.52)
| 1.53 | (0.97–2.39) | |
Year of diagnosis | |||||||
1992–1997 |
2.18
|
(1.31–3.63)
|
2.04
|
(1.16–3.59)
| 1.28 | (0.70–2.35) | |
1998–2002 |
4.02
|
(2.16–7.50)
|
2.93
|
(1.37–6.27)
| 1.80 | (0.78–4.16) | |
2003–2005 | 1.90 | (0.79–4.54) | 1.33 | (0.45–3.95) | 1.17 | (0.37–3.68) | |
Non screening detection |
1.80
|
(1.17–2.78)
| 1.54 | (0.95–2.49) | 1.16 | (0.69–1.96) | |
Positive heredity | 1.47 | (0.84–2.58) | 1.41 | (0.73–2.73) | 1.15 | (0.56–2.35) | |
Tumor size (mm) | |||||||
≤20 |
3.42
|
(1.91–6.12)
|
3.19
|
(1.65–6.20)
| 1.75 | (0.85–3.63) | |
21–50 | 1.60 | (0.93–2.76) | 1.49 | (0.79–2.78) | 1.24 | (0.65–2.37) | |
≥51 | 1.26 | (0.51–3.11) | 0.55 | (0.18–1.70) | 0.23 | (0.03–1.93) | |
Lymph node status | |||||||
Negative |
2.10
|
(1.22–3.62)
|
2.30
|
(1.21–4.39)
| 0.63 | (0.26–1.49) | |
1–3 nodes positive |
2.63
|
(1.33–5.19)
| 1.90 | (0.90–4.00) | 1.20 | (0.50–2.89) | |
≥4 nodes positive | 1.41 | (0.70–2.87) | 1.05 | (0.45–2.41) | 2.05 | (0.94–4.47) | |
Stage | |||||||
I |
3.07
|
(1.41–6.68)
|
3.75
|
(1.58–8.90)
| 1.24 | (0.44–3.48) | |
IIa | 1.55 | (0.82–2.94) | 1.24 | (0.56–2.78) | 0.24 | (0.05–1.06) | |
IIb | 1.71 | (0.71–4.08) | 1.20 | (0.45–3.15) | 0.83 | (0.29–2.39) | |
III | 1.42 | (0.73–2.80) | 1.04 | (0.48–2.27) | 1.94 | (0.92–4.10) | |
Grade | |||||||
I–II |
3.25
|
(1.81–5.81)
|
2.38
|
(1.18–4.81)
| 1.64 | (0.80–3.36) | |
III | 1.46 | (0.87–2.47) | 1.37 | (0.75–2.51) | 0.91 | (0.46–1.83) | |
Estrogen receptor | |||||||
Positive |
2.89
|
(1.85–4.53)
|
2.28
|
(1.36–3.85)
| 1.36 | (0.78–2.39) | |
Negative |
1.91
|
(1.03–3.52)
| 1.85 | (0.91–3.73) | 1.59 | (0.73–3.49) | |
Progesterone receptor | 1.00 (ref.) | ||||||
Positive |
2.77
|
(1.53–5.01)
|
2.45
|
(1.26–4.79)
| 1.10 | (0.52–2.31) | |
Negative |
2.37
|
(1.51–3.73)
|
2.04
|
(1.20–3.48)
|
1.91
|
(1.07–3.41)
| |
Ki67 (%) | |||||||
Low ≤20 |
3.15
|
(1.49–6.67)
| 1.33 | (0.46–3.82) | 1.72 | (0.73–4.06) | |
High ≥21 |
1.70
|
(1.08–2.68)
| 1.65 | (0.98–2.78) | 1.09 | (0.61–1.96) | |
Her2 | |||||||
Negative |
2.36
|
(1.55–3.60)
|
2.15
|
(1.31–3.53)
| 1.27 | (0.74–2.17) | |
Positive | 1.45 | (0.56–3.74) | 0.78 | (0.25–2.46) | 1.38 | (0.42–4.52) | |
Subtype | |||||||
Luminal A | 1.84 | (0.49–6.86) | 0.55 | (0.06–4.67) | 0.29 | (0.03–2.44) | |
Luminal B |
2.30
|
(1.27–4.19)
|
2.30
|
(1.18–4.49)
| 1.64 | (0.82–3.28) | |
Luminal-Her2 | 0.84 | (0.23–3.02) | 0.75 | (0.18–3.16) | 0.75 | (0.13–4.50) | |
Her2-positive | 1.77 | (0.41–7.67) | 0.56 | (0.08–3.98) | 2.20 | (0.40–12.03) | |
Triple-negative | 1.26 | (0.61–2.61) | 1.35 | (0.57–3.21) | 1.09 | (0.39–3.07) | |
Lymphovascular invasion | |||||||
No |
2.66
|
(1.74–4.06)
|
2.12
|
(1.29–3.49)
| 1.14 | (0.64–2.01) | |
Yes | 1.56 | (0.77–3.15) | 1.57 | (0.71–3.47) | 1.60 | (0.71–3.60) | |
Invasive multifocality | |||||||
No |
3.08
|
(2.04–4.63)
|
2.18
|
(1.33–3.55)
| 1.62 | (0.97–2.71) | |
Yes | 1.76 | (0.84–3.71) |
2.26
|
(1.00–5.12)
| 1.12 | (0.43–2.91) | |
Extensive DCIS | |||||||
No |
3.82
|
(1.93–7.54)
|
4.03
|
(1.89–8.62)
| 1.93 | (0.85–4.41) | |
Yes |
5.11
|
(1.20–21.74)
|
5.30
|
(1.19–23.68)
| 4.63 | (0.96–22.27) | |
Locoregional recurrencea
| |||||||
No |
2.75
|
(1.82–4.17)
|
2.11
|
(1.28–3.48)
| 1.53 | (0.91–2.59) | |
Yes | 1.44 | (0.71–2.94) | 1.50 | (0.69–3.27) | 0.96 | (0.40–2.31) |
Multivariate analysis
<35 years | 35–39 years | 40–49 years | 50–69 years | ||||
---|---|---|---|---|---|---|---|
N = 445 |
N = 190 |
N = 192 |
N = 293 | ||||
Breast cancer death | |||||||
Unadjusted |
2.75
|
(1.93–3.94)
|
2.33
|
(1.54–3.52)
| 1.53 | (0.97–2.39) | 1.00 (ref) |
+Year |
2.69
|
(1.88–3.85)
|
2.23
|
(1.48–3.38)
| 1.45 | (0.92–2.28) | |
+Stage |
1.80
|
(1.25–2.60)
| 1.42 | (0.93–2.17) | 1.13 | (0.72–1.78) | |
+Detection mode | 1.39 | (0.93–2.07) | 1.10 | (0.70–1.72) | 0.94 | (0.59–1.50) | |
+Grade | 1.16 | (0.77–1.73) | 0.94 | (0.59–1.49) | 0.85 | (0.53–1.36) | |
+Subtype | 1.10 | (0.73–1.64) | 0.93 | (0.59–1.47) | 0.86 | (0.53–1.38) | |
+Systemic treatment | 1.04 | (0.68–1.58) | 0.88 | (0.55–1.41) | 0.84 | (0.52–1.36) | |
Distant disease | |||||||
Unadjusted |
3.11
|
(2.22–4.36)
|
2.37
|
(1.60–3.53)
|
1.74
|
(1.15–2.64)
| 1.00 (ref) |
+Year |
3.04
|
(2.17–4.26)
|
2.28
|
(1.53–3.39)
|
1.65
|
(1.09–2.50)
| |
+Stage |
2.09
|
(1.48–2.96)
| 1.46 | (0.97–2.18) | 1.29 | (0.85–1.96) | |
+Detection mode |
1.61
|
(1.10–2.35)
| 1.13 | (0.73–1.73) | 1.07 | (0.70–1.66) | |
+Grade | 1.41 | (0.96–2.06) | 1.02 | (0.66–1.57) | 1.00 | (0.65–1.55) | |
+Subtype | 1.40 | (0.96–2.05) | 1.01 | (0.65–1.55) | 1.00 | (0.65–1.55) | |
+Systemic treatment | 1.36 | (0.91–2.02) | 0.97 | (0.62–1.52) | 0.99 | (0.64–1.54) | |
Locoregional recurrence | |||||||
Unadjusted |
3.16
|
(1.98–5.04)
|
2.88
|
(1.70–4.89)
|
1.94
|
(1.11–3.41)
| 1.00 (ref) |
+Year |
3.09
|
(1.94–4.94)
|
2.80
|
(1.65–4.78)
|
1.85
|
(1.05–3.25)
| |
+Stage |
2.88
|
(1.79–4.64)
|
2.60
|
(1.52–4.45)
|
1.78
|
(1.01–3.15)
| |
+Detection mode |
2.38
|
(1.37–4.12)
|
2.15
|
(1.18–3.93)
| 1.58 | (0.87–2.86) | |
+Grade |
2.11
|
(1.21–3.67)
|
1.96
|
(1.07–3.59)
| 1.50 | (0.82–2.72) | |
+Subtype |
2.09
|
(1.20–3.65)
|
1.94
|
(1.06–3.57)
| 1.51 | (0.83–2.74) | |
+Systemic treatment |
2.13
|
(1.21–3.76)
|
1.97
|
(1.06–3.68)
| 1.51 | (0.83–2.75) |