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1Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
2Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
3Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Copyright © 2022 The Korean Society of Coloproctology
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICT OF INTEREST
No potential conflict of interest relevant to this article was reported.
FUNDING
None.
Variable | Synchronous, B=C group (n=21) |
Metachronous |
P-value | ||
---|---|---|---|---|---|
B-first group (n=40) | C-first group (n=44) | ||||
Tumor location | 0.827 | ||||
Right | 8 (38.1) | 18 (45.0) | 22 (50.0) | ||
Left | 13 (61.9) | 21 (52.5) | 21 (47.7) | ||
Bilateral | 0 (0) | 1 (2.5) | 1 (2.3) | ||
Histology type | 0.603 | ||||
In situ | 3 (14.3) | 5 (12.5) | 8 (18.2) | ||
IDC | 15 (71.4) | 32 (80.0) | 30 (68.2) | ||
ILC | 0 (0) | 1 (2.5) | 1 (2.3) | ||
Both | 1 (4.8) | 0 (0) | 0 (0) | ||
Others | 2 (9.5) | 2 (5.0) | 5 (11.4) | ||
T stage (cm) | 0.472 | ||||
Tis | 3 (14.3) | 6 (15.0) | 8 (18.2) | ||
T1 (< 2) | 11 (52.4) | 18 (45.0) | 27 (61.4) | ||
T2 (2–5) | 6 (28.6) | 13 (32.5) | 9 (20.5) | ||
T3 (> 5) | 1 (4.8) | 3 (7.5) | 0 (0) | ||
LN metastasis | 0.224 | ||||
No | 18 (85.7) | 27 (67.5) | 35 (79.5) | ||
Yes | 3 (14.3) (N1: 2, N2: 1, N3: 0) | 13 (32.5) (N1: 9, N2: 1, N3: 3) | 9 (20.5) (N1: 6, N2: 2, N3: 0) | ||
Adjuvant treatment | |||||
No therapy | 1 (4.8) | 1 (2.5) | 5 (11.4) | 0.248 | |
Endocrine therapy | 17 (81.0) | 24 (60.0) | 26 (59.1) | 0.159 | |
Chemotherapy | 4 (19.0) | 23 (57.5) | 9 (20.5) | < 0.001* | |
Radiotherapy | 13 (61.9) | 25 (62.5) | 22 (50.0) | 0.416 | |
Targeted therapy | 1 (4.8) | 4 (10.0) | 2 (4.5) | 0.557 | |
TNM stagea | 0.434 | ||||
0 | 3 (14.3) | 6 (15.0) | 8 (18.2) | ||
1 | 10 (47.6) | 14 (35.0) | 24 (54.5) | ||
2 | 7 (33.3) | 14 (35.0) | 10 (22.7) | ||
3 | 1 (4.8) | 6 (15.0) | 2 (4.5) | ||
Estrogen receptor | 0.242 | ||||
Negative | 3 (14.3) | 10 (25.0) | 15 (34.1) | ||
Positive | 18 (85.7) | 28 (70.0) | 29 (65.9) | ||
Progesterone receptor | 0.490 | ||||
Negative | 9 (42.9) | 15 (37.5) | 23 (52.3) | ||
Positive | 12 (57.1) | 23 (57.5) | 21 (47.7) | ||
Ki-67 (%) | 0.896 | ||||
< 20 | 13 (61.9) | 15 (37.5) | 27 (61.4) | ||
> 20 | 6 (28.6) | 9 (22.5) | 13 (29.5) | ||
HER2 | 0.572 | ||||
Negative | 16 (76.2) | 30 (75.0) | 35 (79.5) | ||
Positive | 4 (19.0) | 8 (20.0) | 5 (11.4) | ||
Molecular classification | 0.384 | ||||
Luminal A | 9 (42.9) | 16 (40.0) | 16 (36.4) | ||
Luminal B | 8 (38.1) | 10 (25.0) | 10 (22.7) | ||
HER2 positive | 1 (4.8) | 5 (12.5) | 2 (4.5) | ||
Triple negative | 2 (9.5) | 6 (15.0) | 12 (27.3) |
Variable | Synchronous, B=C group (n=21) |
Metachronous |
P-value | ||
---|---|---|---|---|---|
B-first group (n=40) | C-first group (n=44) | ||||
Tumor location | 0.194 | ||||
Right-sided colon | 7 (33.3) | 7 (17.5) | 16 (36.4) | ||
Left-sided colon | 9 (42.9) | 17 (42.5) | 10 (22.7) | ||
Rectum | 5 (23.8) | 15 (37.5) | 18 (40.9) | ||
Appendix | 1 (4.8) | 1 (2.5) | 0 (0) | ||
Treatment | 0.044* | ||||
Endoscopic treatment | 1 (4.8) | 8 (20.0) | 2 (4.5) | ||
Surgery | 20 (95.2) | 32 (80.0) | 42 (95.5) | ||
Histologic type | 0.247 | ||||
Adenocarcinoma | 21 (100) | 40 (100) | 43 (97.7) | ||
Signet ring cell | 0 (0) | 0 (0) | 1 (2.3) | ||
T stage | 0.604 | ||||
Tis | 1 (4.8) | 5 (12.5) | 4 (9.1) | ||
T1 | 2 (9.5) | 9 (22.5) | 8 (18.2) | ||
T2 | 2 (9.5) | 7 (17.5) | 7 (15.9) | ||
T3 | 13 (61.9) | 15 (37.5) | 23 (52.3) | ||
T4 | 3 (14.3) | 4 (10.0) | 2 (4.5) | ||
LN metastasis | 0.278 | ||||
No | 12 (57.1) | 31 (77.5) | 31 (70.5) | ||
Yes | 9 (42.9) (N1: 6, N2: 3, N3:0) | 9 (22.5) (N1: 6, N2: 3, N3:0) | 13 (29.5) (N1: 8, N2: 5, N3:0) | ||
TNM stage | 0.698 | ||||
0 | 1 (4.8) | 5 (12.5) | 4 (9.1) | ||
1 | 4 (19.0) | 14 (35.0) | 14 (31.8) | ||
2 | 7 (33.3) | 12 (30.0) | 14 (31.8) | ||
3 | 9 (42.9) | 9 (22.5) | 12 (27.3) |
Characteristic | Synchronous, B = C group | Metachronous |
P-value | ||
---|---|---|---|---|---|
B-first group | C-first group | ||||
No. of patients | 21 | 40 | 44 | ||
Sex | 0.497 | ||||
Male | 0 (0) | 0 (0) | 1 (2.3) | ||
Female | 21 (100) | 40 (100) | 43 (97.7) | ||
Age (yr) | |||||
The first primary cancer | 63.0 ± 9.9 (43–82) | 57.0 ± 10.1 (34–73) | 59.6 ± 10.5 (33–78) | 0.093 | |
The second primary cancer | 63.0 ± 9.9 (43–82) | 62.5 ± 9.6 (40–80) | 64.7 ± 10.7 (41–82) | 0.596 | |
Interval between diagnosis of BrC and CRC (mo) | 0.5 ± 1.3 (0–5) | 67.1 ± 40.4 (7–183) | 59.3 ± 47.2 (6–223) | > 0.999 | |
BMI at diagnosis of the first cancer (kg/m2) | 23.2 ± 2.8 (19.4–30.4) | 23.5 ± 3.5 (17.2–31.6) | 24.2 ± 4.1 (16.5–32.8) | 0.540 | |
Comorbidity | |||||
Hypertension | 5 (23.8) | 19 (47.5) | 19 (43.2) | 0.187 | |
Diabetes mellitus | 0 (0.0) | 13 (32.5) | 8 (18.2) | 0.010 | |
Previous cancer history | 1 (4.8) | 6 (15.0) | 6 (13.6) | 0.487 | |
Familial cancer history | |||||
BrC | 2 (9.5) | 2 (5.0) | 5 (11.4) | 0.573 | |
CRC | 2 (9.5) | 1 (2.5) | 4 (9.1) | 0.405 | |
Both | 0 (0) | 0 (0) | 1 (2.3) | 0.480 | |
Other cancers | 5 (23.8) | 11 (27.5) | 11 (25.0) | 0.943 | |
Tumor marker at BrC diagnosis | |||||
CEA (ng/mL) | 8.1 ± 11.4 (0.5–41.3) | 2.1 ± 1.4 (0.5–5.8) | 4.0 ± 11.8 (0.6–73.9) | 0.112 | |
CA 15-3 (U/mL) | 13.3 ± 8.4 (2.9–28.4) | 10.5 ± 4.6 (4.4–21.3) | 11.9 ± 6.7 (1.8–30.6) | 0.369 | |
Tumor marker at CRC diagnosis | |||||
CEA (ng/mL) | 8.5±17.5 (0.9–77.5) | 3.3±3.2 (0.6–12.7) | 7.5±17.0 (0.4–87.1) | 0.288 |
Variable | Synchronous, B=C group (n=21) | Metachronous |
P-value | ||
---|---|---|---|---|---|
B-first group (n=40) | C-first group (n=44) | ||||
Tumor location | 0.827 | ||||
Right | 8 (38.1) | 18 (45.0) | 22 (50.0) | ||
Left | 13 (61.9) | 21 (52.5) | 21 (47.7) | ||
Bilateral | 0 (0) | 1 (2.5) | 1 (2.3) | ||
Histology type | 0.603 | ||||
In situ | 3 (14.3) | 5 (12.5) | 8 (18.2) | ||
IDC | 15 (71.4) | 32 (80.0) | 30 (68.2) | ||
ILC | 0 (0) | 1 (2.5) | 1 (2.3) | ||
Both | 1 (4.8) | 0 (0) | 0 (0) | ||
Others | 2 (9.5) | 2 (5.0) | 5 (11.4) | ||
T stage (cm) | 0.472 | ||||
Tis | 3 (14.3) | 6 (15.0) | 8 (18.2) | ||
T1 (< 2) | 11 (52.4) | 18 (45.0) | 27 (61.4) | ||
T2 (2–5) | 6 (28.6) | 13 (32.5) | 9 (20.5) | ||
T3 (> 5) | 1 (4.8) | 3 (7.5) | 0 (0) | ||
LN metastasis | 0.224 | ||||
No | 18 (85.7) | 27 (67.5) | 35 (79.5) | ||
Yes | 3 (14.3) (N1: 2, N2: 1, N3: 0) | 13 (32.5) (N1: 9, N2: 1, N3: 3) | 9 (20.5) (N1: 6, N2: 2, N3: 0) | ||
Adjuvant treatment | |||||
No therapy | 1 (4.8) | 1 (2.5) | 5 (11.4) | 0.248 | |
Endocrine therapy | 17 (81.0) | 24 (60.0) | 26 (59.1) | 0.159 | |
Chemotherapy | 4 (19.0) | 23 (57.5) | 9 (20.5) | < 0.001 |
|
Radiotherapy | 13 (61.9) | 25 (62.5) | 22 (50.0) | 0.416 | |
Targeted therapy | 1 (4.8) | 4 (10.0) | 2 (4.5) | 0.557 | |
TNM stage |
0.434 | ||||
0 | 3 (14.3) | 6 (15.0) | 8 (18.2) | ||
1 | 10 (47.6) | 14 (35.0) | 24 (54.5) | ||
2 | 7 (33.3) | 14 (35.0) | 10 (22.7) | ||
3 | 1 (4.8) | 6 (15.0) | 2 (4.5) | ||
Estrogen receptor | 0.242 | ||||
Negative | 3 (14.3) | 10 (25.0) | 15 (34.1) | ||
Positive | 18 (85.7) | 28 (70.0) | 29 (65.9) | ||
Progesterone receptor | 0.490 | ||||
Negative | 9 (42.9) | 15 (37.5) | 23 (52.3) | ||
Positive | 12 (57.1) | 23 (57.5) | 21 (47.7) | ||
Ki-67 (%) | 0.896 | ||||
< 20 | 13 (61.9) | 15 (37.5) | 27 (61.4) | ||
> 20 | 6 (28.6) | 9 (22.5) | 13 (29.5) | ||
HER2 | 0.572 | ||||
Negative | 16 (76.2) | 30 (75.0) | 35 (79.5) | ||
Positive | 4 (19.0) | 8 (20.0) | 5 (11.4) | ||
Molecular classification | 0.384 | ||||
Luminal A | 9 (42.9) | 16 (40.0) | 16 (36.4) | ||
Luminal B | 8 (38.1) | 10 (25.0) | 10 (22.7) | ||
HER2 positive | 1 (4.8) | 5 (12.5) | 2 (4.5) | ||
Triple negative | 2 (9.5) | 6 (15.0) | 12 (27.3) |
Variable | Synchronous, B=C group (n=21) | Metachronous |
P-value | ||
---|---|---|---|---|---|
B-first group (n=40) | C-first group (n=44) | ||||
Tumor location | 0.194 | ||||
Right-sided colon | 7 (33.3) | 7 (17.5) | 16 (36.4) | ||
Left-sided colon | 9 (42.9) | 17 (42.5) | 10 (22.7) | ||
Rectum | 5 (23.8) | 15 (37.5) | 18 (40.9) | ||
Appendix | 1 (4.8) | 1 (2.5) | 0 (0) | ||
Treatment | 0.044 |
||||
Endoscopic treatment | 1 (4.8) | 8 (20.0) | 2 (4.5) | ||
Surgery | 20 (95.2) | 32 (80.0) | 42 (95.5) | ||
Histologic type | 0.247 | ||||
Adenocarcinoma | 21 (100) | 40 (100) | 43 (97.7) | ||
Signet ring cell | 0 (0) | 0 (0) | 1 (2.3) | ||
T stage | 0.604 | ||||
Tis | 1 (4.8) | 5 (12.5) | 4 (9.1) | ||
T1 | 2 (9.5) | 9 (22.5) | 8 (18.2) | ||
T2 | 2 (9.5) | 7 (17.5) | 7 (15.9) | ||
T3 | 13 (61.9) | 15 (37.5) | 23 (52.3) | ||
T4 | 3 (14.3) | 4 (10.0) | 2 (4.5) | ||
LN metastasis | 0.278 | ||||
No | 12 (57.1) | 31 (77.5) | 31 (70.5) | ||
Yes | 9 (42.9) (N1: 6, N2: 3, N3:0) | 9 (22.5) (N1: 6, N2: 3, N3:0) | 13 (29.5) (N1: 8, N2: 5, N3:0) | ||
TNM stage | 0.698 | ||||
0 | 1 (4.8) | 5 (12.5) | 4 (9.1) | ||
1 | 4 (19.0) | 14 (35.0) | 14 (31.8) | ||
2 | 7 (33.3) | 12 (30.0) | 14 (31.8) | ||
3 | 9 (42.9) | 9 (22.5) | 12 (27.3) |
Variable | Univariate analysis |
Multivariate analysis |
|||
---|---|---|---|---|---|
HR (95% CI) | P-value | HR (95% CI) | P-value | ||
Group | |||||
B-first group | Reference | Reference | |||
C-first group | 0.23 (0.04–1.23) | 0.086 | 0.28 (0.03–2.30) | 0.235 | |
B = C group | 0.22 (0.01–5.65) | 0.364 | 0.25 (0.01–7.90) | 0.428 | |
Age at BrC diagnosis | 0.98 (0.92–1.05) | 0.615 | |||
Age at CRC diagnosis | 0.99 (0.93–1.07) | 0.900 | |||
CEA at CRC diagnosis | 0.99 (0.89–1.09) | 0.784 | |||
CA15-3 at BrC diagnosis | 0.98 (0.84–1.15) | 0.804 | |||
BrC histology | |||||
In situ cancer | Reference | ||||
IDC | 0.91 (0.10–8.03) | 0.935 | |||
Others | 1.14 (0.07–18.98) | 0.927 | |||
BrC T stage | |||||
T0 | Reference | ||||
T1 | 1.06 (0.11–9.83) | 0.960 | |||
T2 | 0.49 (0.03–8.34) | 0.620 | |||
T3 | 7.95 (0.49–128.96) | 0.145 | |||
BrC LN metastasis | |||||
No | Reference | ||||
Yes | 2.01 (0.44–9.17) | 0.368 | |||
Hormone receptora | |||||
Negative | Reference | ||||
Positive | 0.99 (0.18–5.44) | 0.986 | |||
HER2 | |||||
Negative | Reference | Reference | |||
Positive | 11.93 (1.24–115.08) | 0.032* | 7.07 (0.82–61.36) | 0.076 | |
Molecular classification | |||||
Luminal A | Reference | ||||
Luminal B | 1.12 (0.10–12.99) | 0.931 | |||
HER2 enriched | 8.71 (0.88–86.44) | 0.065 | |||
Triple negative | 0.25 (0.01–9.36) | 0.453 | |||
CRC T stage | |||||
T0 | Reference | ||||
T1 | 0.92 (0.02–40.70) | 0.966 | |||
T2 | 1.14 (0.03–49.01) | 0.947 | |||
T3 | 1.26 (0.04–39.01) | 0.895 | |||
T4 | 2.35 (0.06–101.05) | 0.657 | |||
CRC LN metastasis | |||||
No | Reference | Reference | |||
Yes | 5.81 (1.13–29.98) | 0.036* | 5.44 (0.72–41.29) | 0.102 | |
BrC TNM stage | |||||
0 | Reference | ||||
1 | 0.96 (0.100–9.37) | 0.969 | |||
2 | 1.01 (0.09–11.65) | 0.994 | |||
3 | 1.92 (0.12–31.53) | 0.647 | |||
CRC TNM stage | |||||
0 | Reference | ||||
1 | 0.54 (0.01–21.73) | 0.746 | |||
2 | 0.69 (0.02–26.96) | 0.844 | |||
3 | 2.45 (0.09–68.03) | 0.598 |
Values are presented as mean±standard deviation (range) or number of patients (%). BrC, breast cancer; CRC, colorectal cancer; BMI, body mass index; CEA, carcinoembryonic antigen; CA 15-3, carcinoma antigen 15-3.
Values are presented as number of patients (%). IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LN, lymph node; HER2, human epidermal growth factor receptor 2. Stage according to American Joint Committee on Cancer cancer stage manual, 8th edition. P<0.05.
Values are presented as number of patients (%). LN, lymph node. P<0.05.
HR, hazard ratio; CI, confidence interval; BrC, breast cancer; CRC, colorectal cancer; CEA, carcinoembryonic antigen; CA 15-3, carcinoma antigen 15-3; IDC, invasive ductal carcinoma; HER2, human epidermal growth factor receptor 2; LN, lymph node. Estrogen or progesterone. P<0.05.