Background
Methods
Ethical statement
Data source and study cohort
Study endpoints and definition
Statistical analysis
Results
Baseline clinicopathological description of OBC cohort
Characteristic | Number of patients | Percentage (%) |
---|---|---|
N | 1189 | 100 |
Age (year) | ||
< 40 | 54 | 4.54 |
40–49 | 176 | 14.80 |
50–59 | 348 | 29.27 |
60–69 | 343 | 28.85 |
≥ 70 | 268 | 22.54 |
Mean of age (year) | 59.88 | |
Median of age (year, range) | 60.00 (26–85) | |
Race | ||
White | 942 | 79.23 |
Black | 139 | 11.69 |
Asian or Pacific Islander | 95 | 7.99 |
American Indian/Alaska Native | 9 | 0.76 |
Unknown/other | 4 | 0.34 |
Marital status | ||
Not married | 449 | 37.76 |
Married | 699 | 58.79 |
Unknown | 41 | 3.45 |
Grade | ||
I/II | 65 | 5.47 |
III | 223 | 18.76 |
IV | 10 | 0.84 |
Unknown | 891 | 74.94 |
Laterality | ||
Right | 565 | 47.52 |
Left | 624 | 52.48 |
Histology | ||
Ductal carcinoma | 476 | 40.03 |
Lobular carcinoma | 54 | 4.54 |
Mixed type | 25 | 2.10 |
Other | 634 | 53.32 |
N | ||
N1mi | 31 | 2.61 |
N1 | 721 | 60.64 |
N2 | 228 | 19.18 |
N3 | 209 | 17.58 |
No. of examined LN | ||
1–3 | 182 | 15.31 |
4–9 | 177 | 14.89 |
≥ 10 | 675 | 56.77 |
Other/unknown | 155 | 13.04 |
No. of positive LN | ||
1–3 | 615 | 51.72 |
4–9 | 212 | 17.83 |
≥ 10 | 148 | 12.45 |
Other/unknown | 214 | 18.00 |
Stage | ||
IB | 31 | 2.61 |
IIA | 722 | 60.72 |
IIIA | 228 | 19.18 |
IIIC | 208 | 17.49 |
Surgery | ||
BCS | 120 | 10.09 |
Mastectomy | 422 | 35.49 |
None/unknown | 647 | 54.42 |
Radiation | ||
Yes | 688 | 57.86 |
None/unknown | 501 | 42.13 |
Chemotherapy | ||
Yes | 929 | 78.13 |
No/unknown | 260 | 21.87 |
Type of systemic therapy | ||
Neoadjuvant | 118 | 9.92 |
Adjuvant | 583 | 49.03 |
Neoadjuvant + adjuvant | 104 | 8.75 |
Only systemic therapy, no surgery | 28 | 2.35 |
Other | 190 | 15.98 |
No/unknown | 166 | 13.96 |
Subtypes | ||
Luminal A | 326 | 27.42 |
Luminal B | 111 | 9.34 |
HER2 positive | 74 | 6.22 |
Triple negative | 148 | 12.45 |
Unknown | 530 | 44.58 |
ER | ||
Negative | 414 | 34.82 |
Borderline/unknown | 100 | 8.41 |
Positive | 675 | 56.77 |
PR | ||
Negative | 598 | 50.29 |
Borderline/unknown | 126 | 10.60 |
Positive | 465 | 39.11 |
HER2 | ||
Negative | 474 | 39.87 |
Positive | 187 | 15.73 |
Unknown | 528 | 44.41 |
Vital status | ||
Alive | 917 | 77.12 |
Dead | 272 | 22.88 |
Comparison of clinicopathological features in different treatment
Variables | Surgery | P-value | |||
---|---|---|---|---|---|
BCT | Mastectomy | ||||
N | Percentage (%) | N | Percentage (%) | ||
N | 748 | 100 | 422 | 100 | |
Age | < 0.001 | ||||
< 40 | 24 | 3.21 | 29 | 6.87 | |
40–49 | 91 | 12.17 | 83 | 19.67 | |
50–59 | 216 | 28.88 | 126 | 29.86 | |
60–69 | 223 | 29.81 | 114 | 27.01 | |
≥ 70 | 194 | 25.94 | 70 | 16.59 | |
Mean (± SD) | 61.16 ± 11.35 | 57.65 ± 11.72 | < 0.001* | ||
Race | 0.14** | ||||
White | 587 | 78.48 | 340 | 80.57 | |
Black | 92 | 12.30 | 45 | 10.66 | |
Asian or Pacific Islander | 57 | 7.62 | 36 | 8.53 | |
American Indian/Alaska Native | 9 | 1.20 | 0 | 0 | |
Unknown/other | 3 | 0.40 | 1 | 0.24 | |
Marital status | 0.64 | ||||
Not married | 289 | 34.17 | 153 | 36.3 | |
Married | 433 | 61.67 | 256 | 60.7 | |
Unknown | 26 | 4.17 | 13 | 3.1 | |
Grade | 0.30 | ||||
I/II | 35 | 4.68 | 28 | 6.64 | |
III | 135 | 18.05 | 85 | 20.14 | |
IV | 7 | 0.94 | 2 | 0.47 | |
Unknown | 571 | 76.34 | 307 | 72.75 | |
Laterality | 0.15 | ||||
Right | 342 | 45.72 | 212 | 50.24 | |
Left | 406 | 54.28 | 210 | 49.76 | |
Histology | 0.04 | ||||
Ductal carcinoma | 277 | 37.03 | 192 | 45.50 | |
Lobular carcinoma | 37 | 4.95 | 16 | 3.79 | |
Mixed type | 16 | 2.14 | 9 | 2.13 | |
Other | 418 | 55.88 | 205 | 48.58 | |
N | < 0.001 | ||||
N1mi | 12 | 1.60 | 19 | 4.50 | |
N1 | 481 | 64.30 | 226 | 53.55 | |
N2 | 131 | 17.51 | 95 | 22.51 | |
N3 | 124 | 16.58 | 82 | 19.43 | |
No. of examined LN | < 0.001 | ||||
1–3 | 131 | 17.51 | 49 | 11.61 | |
4–9 | 100 | 13.37 | 72 | 17.06 | |
≥ 10 | 390 | 52.14 | 276 | 65.40 | |
Other/Unknown | 127 | 16.98 | 25 | 5.92 | |
No. of positive LN | < 0.001 | ||||
1–3 | 376 | 50.27 | 227 | 53.79 | |
4–9 | 117 | 15.64 | 93 | 22.04 | |
≥ 10 | 86 | 11.50 | 60 | 14.22 | |
Other/Unknown | 169 | 22.59 | 42 | 9.95 | |
Stage | < 0.001 | ||||
IB | 12 | 1.60 | 19 | 4.50 | |
IIA | 481 | 64.30 | 226 | 53.55 | |
IIIA | 131 | 17.51 | 96 | 22.75 | |
IIIC | 124 | 16.58 | 81 | 19.19 | |
Radiation | < 0.001 | ||||
Yes | 462 | 61.76 | 215 | 50.95 | |
None/Unknown | 286 | 38.24 | 207 | 49.05 | |
Chemotherapy | 0.003 | ||||
Yes | 566 | 75.67 | 351 | 83.18 | |
No/Unknown | 182 | 24.33 | 71 | 16.82 | |
Type of systemic therapy | < 0.001 | ||||
Neoadjuvant | 61 | 8.16 | 55 | 13.03 | |
Adjuvant | 380 | 50.80 | 196 | 46.45 | |
Neoadjuvant + adjuvant | 49 | 6.55 | 54 | 12.80 | |
Only systemic therapy, no surgery | 28 | 3.74 | 0 | 0 | |
Other | 113 | 15.11 | 74 | 17.54 | |
No/Unknown | 117 | 15.64 | 43 | 10.19 | |
Subtypes | 0.48 | ||||
Luminal A | 214 | 28.61 | 106 | 25.12 | |
Luminal B | 65 | 8.69 | 44 | 10.43 | |
HER2 + | 51 | 6.82 | 23 | 5.45 | |
Triple negative | 93 | 12.43 | 52 | 12.32 | |
Unknown | 325 | 43.45 | 197 | 46.68 | |
ER | 0.89 | ||||
Negative | 259 | 34.63 | 149 | 35.31 | |
Borderline/Unknown | 61 | 8.16 | 37 | 8.77 | |
Positive | 428 | 57.22 | 236 | 55.92 | |
PR | 0.76 | ||||
Negative | 372 | 49.73 | 215 | 50.95 | |
Borderline/Unknown | 77 | 10.29 | 47 | 11.14 | |
Positive | 299 | 39.97 | 160 | 37.91 | |
HER2 | 0.44 | ||||
Negative | 307 | 41.04 | 158 | 37.44 | |
Positive | 118 | 15.78 | 67 | 15.88 | |
Unknown | 323 | 43.18 | 197 | 46.68 |
Survival analysis in OBC cohort
Variables | OS | BCSS | ||||
---|---|---|---|---|---|---|
HR | 95% CI | P-value | HR | 95% CI | P-value | |
Age (year) | 1.05 | 1.03–1.06 | < 0.0001 | 1.03 | 1.02–1.04 | < 0.001 |
< 40 | Reference | Reference | ||||
40–49 | 0.63 | 0.31–1.31 | 0.22 | 0.82 | 0.34–1.97 | 0.66 |
50–59 | 0.93 | 0.49–1.77 | 0.83 | 0.99 | 0.44–2.20 | 0.98 |
60–69 | 1.14 | 0.60–2.16 | 0.68 | 1.10 | 0.50–2.45 | 0.81 |
≥ 70 | 2.69 | 1.44–5.01 | 0.002 | 2.03 | 0.93–4.46 | 0.08 |
Race | ||||||
White | Reference | Reference | ||||
Black | 1.30 | 0.93–1.81 | 0.12 | 0.88 | 0.55–1.42 | 0.61 |
Asian or Pacific Islander | 0.75 | 0.44–1.26 | 0.28 | 0.37 | 0.15–0.89 | 0.03 |
American Indian/Alaska Native | 1.11 | 0.28–4.49 | 0.88 | 1.78 | 0.44–7.17 | 0.42 |
Unknown/other | 8.34 × 10–7 | 0-INF | 0.99 | 7.65 × 10−7 | 0-INF | 0.99 |
Marital status | ||||||
Not married | Reference | Reference | ||||
Married | 0.71 | 0.56–0.91 | 0.007 | 0.77 | 0.56–1.06 | 0.11 |
Unknown | 1.25 | 0.69–2.26 | 0.47 | 1.31 | 0.63–2.72 | 0.47 |
Grade | ||||||
I/II | Reference | Reference | ||||
III | 2.59 | 1.03–6.54 | 0.04 | 2.59 | 1.03–6.54 | 0.04 |
IV | 0.99 | 0.12–8.52 | 1.00 | 0.99 | 0.12–8.52 | 1.00 |
Unknown | 1.81 | 0.74–4.42 | 0.20 | 1.81 | 0.74–4.42 | 0.20 |
Laterality | ||||||
Right | Reference | Reference | ||||
Left | 1.03 | 0.81–1.31 | 0.79 | 1.11 | 0.82–1.51 | 0.50 |
Histology | ||||||
Ductal carcinoma | Reference | Reference | ||||
Lobular carcinoma | 0.85 | 0.44–1.62 | 0.61 | 1.24 | 0.59–2.60 | 0.57 |
Mixed type | 0.69 | 0.28–1.70 | 0.43 | 0.77 | 0.24–2.47 | 0.67 |
Other | 0.85 | 0.66–1.08 | 0.18 | 1.03 | 0.75–1.43 | 0.84 |
N | ||||||
N1mi | Reference | Reference | ||||
N1 | 2.15 | 0.53–8.70 | 0.28 | 1.01 | 0.32–16.46 | 0.41 |
N2 | 2.84 | 0.69–11.67 | 0.15 | 1.01 | 0.64–33.65 | 0.13 |
N3 | 4.00 | 0.98–16.32 | 0.05 | 1.01 | 1.04–54.08 | 0.05 |
No. of positive LN | ||||||
1–3 | Reference | Reference | ||||
4–9 | 1.82 | 1.32–2.52 | < 0.001 | 2.77 | 1.79–4.28 | < 0.001 |
≥ 10 | 2.22 | 1.59–3.10 | < 0.001 | 4.42 | 2.91–6.71 | < 0.001 |
Other/Unknown | 1.01 | 1.99–3.77 | < 0.001 | 4.09 | 2.67–6.25 | < 0.001 |
Stage | ||||||
IB | Reference | Reference | ||||
IIA | 2.15 | 0.53–8.70 | 0.28 | 1.01 | 0.32–16.46 | 0.4123 |
IIIA | 2.84 | 0.69–11.63 | 0.15 | 1.01 | 0.63–33.51 | 0.1312 |
IIIC | 4.02 | 0.98–16.40 | 0.05 | 1.01 | 1.04–54.37 | 0.0453 |
Surgery | ||||||
BCS | Reference | Reference | ||||
Mastectomy | 0.82 | 0.53–1.26 | 0.36 | 1.08 | 0.60–1.94 | 0.80 |
None/Unknown | 1.13 | 0.76–1.69 | 0.55 | 1.44 | 0.82–2.52 | 0.20 |
Radiation | ||||||
None/Unknown | Reference | Reference | ||||
Yes | 0.66 | 0.52–0.84 | 0.0007 | 0.70 | 0.52–0.95 | 0.02 |
Chemotherapy | ||||||
Yes | Reference | Reference | ||||
No/Unknown | 0.55 | 0.43–0.71 | < 0.001 | 0.73 | 0.52–1.02 | 0.07 |
Type of systemic therapy | ||||||
Neoadjuvant | Reference | Reference | ||||
Adjuvant | 0.97 | 0.61–1.55 | 0.91 | 0.92 | 0.53–1.60 | 0.76 |
Neoadjuvant + adjuvant | 0.53 | 0.24–1.15 | 0.11 | 0.73 | 0.32–1.66 | 0.45 |
Only systemic therapy, no surgery | 3.42 | 1.71–6.83 | 0.0005 | 3.58 | 1.61–7.97 | 0.002 |
Other | 0.27 | 0.37–1.08 | 0.09 | 0.52 | 0.27–1.04 | 0.06 |
No/Unknown | 0.25 | 1.01–2.70 | 0.04 | 1.39 | 0.76–2.53 | 0.28 |
Subtypes | ||||||
Luminal A | Reference | Reference | ||||
Luminal B | 0.62 | 0.30–1.27 | 0.19 | 0.69 | 0.28–1.66 | 0.40 |
HER2 positive | 1.31 | 0.70–2.43 | 0.40 | 1.80 | 0.89–3.64 | 0.10 |
Triple negative | 1.63 | 1.03–2.57 | 0.04 | 2.03 | 1.17–3.54 | 0.01 |
Unknown | 1.28 | 0.91–1.81 | 0.16 | 1.52 | 0.98–2.35 | 0.06 |
ER | ||||||
Negative | Reference | Reference | ||||
Borderline/Unknown | 1.08 | 0.73–1.61 | 0.70 | 1.18 | 0.73–1.90 | 0.50 |
Positive | 0.71 | 0.55–0.92 | 0.009 | 0.59 | 0.43–0.81 | 0.001 |
PR | ||||||
Negative | Reference | Reference | ||||
Borderline/Unknown | 1.08 | 0.76 -1.56 | 0.66 | 1.06 | 0.68–1.66 | 0.80 |
Positive | 0.78 | 0.60–1.01 | 0.06 | 0.54 | 0.38–0.77 | 0.0007 |
HER2 | ||||||
Negative | Reference | Reference | ||||
Positive | 0.74 | 0.46–1.19 | 0.21 | 0.85 | 0.49–1.47 | 0.56 |
Unknown | 1.08 | 0.81–1.43 | 0.62 | 1.15 | 0.81–1.63 | 0.43 |
Variables | OS | BCSS | ||||
---|---|---|---|---|---|---|
HR | 95% CI | P-value | HR | 95% CI | P-value | |
Age (year) | ||||||
< 40 | Reference | |||||
40–49 | 0.57 | 0.27–1.19 | 0.13 | 0.64 | 0.26–1.56 | 0.32 |
50–59 | 0.82 | 0.43–1.58 | 0.56 | 0.82 | 0.36–1.85 | 0.64 |
60–69 | 1.04 | 0.55–1.99 | 0.90 | 0.97 | 0.43–2.18 | 0.93 |
≥ 70 | 2.15 | 1.13–4.08 | 0.02 | 1.52 | 0.67–3.41 | 0.31 |
Race | ||||||
White | Reference | Reference | ||||
Black | – | – | – | 0.90 | 0.56–1.47 | 0.68 |
Asian or Pacific Islander | – | – | – | 0.39 | 0.16–0.97 | 0.04 |
American Indian/Alaska Native | – | – | – | 4.25 | 1.01–17.99 | 0.05 |
Unknown/other | – | – | – | 1.23 × 10–6 | 0-INF | 0.99 |
Marital status | ||||||
Not married | Reference | – | – | – | ||
Married | 0.80 | 0.62–1.02 | 0.07 | – | – | – |
Unknown | 1.25 | 0.68–2.31 | 0.48 | – | – | – |
Grade | ||||||
I/II | Reference | Reference | ||||
III | 0.90 | 0.51–1.59 | 0.71 | 1.71 | 0.65–4.47 | 0.27 |
IV | 0.66 | 0.22–2.04 | 0.47 | 0.65 | 0.07–5.73 | 0.70 |
Unknown | 0.70 | 0.41–1.19 | 0.18 | 1.26 | 0.50–3.16 | 0.63 |
N | ||||||
N1mi | Reference | Reference | ||||
N1 | 1.34 × 1011 | 0-INF | 0.99 | 1.17 × 1013 | 0-INF | 1.00 |
N2 | 1.72 × 106 | 0-INF | 0.99 | 4.04 × 107 | 0-INF | 1.00 |
N3 | 3.44 | 0.79–14.92 | 0.10 | 4.47 | 0.58–34.38 | 0.15 |
No. of positive LN | ||||||
1–3 | Reference | Reference | ||||
4–9 | 2.09 | 1.17–3.73 | 0.01 | 1.96 | 0.95–4.02 | 0.07 |
≥ 10 | 1.53 | 0.86–2.73 | 0.15 | 2.28 | 1.16–4.46 | 0.02 |
Other/Unknown | 2.47 | 1.76–3.47 | < 0.001 | 3.26 | 2.07–5.13 | < 0.001 |
Stage | ||||||
IB | Reference | Reference | ||||
IIA | 1.39 × 10–11 | 0-INF | 0.99 | 1.45 × 10–13 | 0-INF | 1.00 |
IIIA | 9.80 × 10–7 | 0-INF | 0.99 | 6.46 × 10–8 | 0-INF | 1.00 |
IIIC | NA | NA | NA | NA | NA | NA |
Radiation | ||||||
None/Unknown | Reference | Reference | ||||
Yes | 0.68 | 0.52–0.88 | 0.003 | 0.63 | 0.45–0.88 | 0.007 |
Chemotherapy | ||||||
Yes | Reference | Reference | ||||
No/Unknown | 0.87 | 0.52–1.44 | 0.59 | 1.08 | 0.51–2.28 | 0.84 |
Type of systemic therapy | ||||||
Neoadjuvant | Reference | Reference | ||||
Adjuvant | 0.93 | 0.58–1.50 | 0.77 | 1.00 | 0.57–1.75 | 0.99 |
Neoadjuvant + adjuvant | 0.50 | 0.23–1.10 | 0.08 | 0.69 | 0.30–1.59 | 0.38 |
Only systemic therapy, no surgery | 1.88 | 0.90–3.90 | 0.09 | 2.40 | 1.03–5.60 | 0.04 |
Other | 0.55 | 0.32–0.96 | 0.04 | 0.46 | 0.23–0.93 | 0.03 |
No/Unknown | 1.02 | 0.51–2.06 | 0.95 | 1.23 | 0.48–3.17 | 0.67 |
Subtypes | ||||||
Luminal A | Reference | Reference | ||||
Luminal B | 0.63 | 0.31–1.31 | 0.22 | 0.65 | 0.26–1.60 | 0.35 |
HER2 positive | 1.10 | 0.54–2.22 | 0.79 | 1.31 | 0.56–3.02 | 0.53 |
Triple negative | 1.42 | 0.81–2.50 | 0.22 | 1.66 | 0.81–3.40 | 0.17 |
Unknown | 1.53 | 1.02–2.27 | 0.04 | 1.64 | 0.97–2.76 | 0.06 |
ER | ||||||
Negative | Reference | Reference | ||||
Borderline/Unknown | 1.13 | 0.51–2.54 | 0.76 | 1.63 | 0.63- 4.18 | 0.31 |
Positive | 0.78 | 0.53–1.14 | 0.20 | 0.87 | 0.52–1.43 | 0.57 |
PR | ||||||
Negative | Reference | Reference | ||||
Borderline/Unknown | 0.85 | 0.41–1.79 | 0.68 | 0.72 | 0.29–1.74 | 0.46 |
Positive | 0.99 | 0.69–1.43 | 0.98 | 0.78 | 0.49–1.24 | 0.30 |