| Literature DB >> 28389735 |
Elvira L Vos1, Sabine Siesling2,3, Margreet H A Baaijens4, Cornelis Verhoef1, Agnes Jager5, Adri C Voogd2,6, Linetta B Koppert7.
Abstract
PURPOSE: In contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study.Entities:
Keywords: Breast-conserving surgery; Disease-free survival; Ipsilateral breast tumor recurrence; Overall survival; Re-excision; Re-operation; Resection margins
Mesh:
Year: 2017 PMID: 28389735 PMCID: PMC5487695 DOI: 10.1007/s10549-017-4232-6
Source DB: PubMed Journal: Breast Cancer Res Treat ISSN: 0167-6806 Impact factor: 4.872
Fig. 1Patient selection. cM1 clinically suspect distant metastasis, pM1 pathologically confirmed distant metastasis, pTX primary tumor cannot be assessed or is unknown, pT0 no evidence of primary tumor, pT4 tumor with direct extension to the chest wall and/or to the skin, BCS breast-conserving surgery. §Except for basal-like skin cancer. *Follow-up information on disease recurrence was assembled for all patients diagnosed in 2003–2006, and for 44% of the patients diagnosed in 2007–2008 due to lack of funding for some hospitals. †All patients of whom the breast was conserved had adjuvant radiotherapy. From all patients with a re-excision by mastectomy, 873 (22.5%) had adjuvant radiotherapy. ‡Since it was an optional item in the coding manual, some registration clerks did not code margins
Clinicopathological and treatment characteristics according to the performance of re-excision in the total cohort (n = 32119)
| Primary BCS only | Primary BCS + re-excision by BCS | Primary BCS + re-excision by mastectomy |
| |
|---|---|---|---|---|
| No. of patients | 25878 (80.6) | 2368 (7.4) | 3873 (12.1) | |
| Age | <0.001 | |||
| >60 years | 10505 (40.6) | 718 (30.3) | 1185 (30.6) | |
| 51–60 years | 7946 (30.7) | 780 (32.9) | 1113 (28.7) | |
| 41–50 years | 5795 (22.4) | 681 (28.8) | 1152 (29.7) | |
| ≤40 years | 1632 (6.3) | 189 (8.0) | 423 (10.9) | |
| Histology | <0.001 | |||
| Ductal | 20148 (77.9) | 1797 (77.9) | 2548 (65.8) | |
| Lobularb | 2841 (11.0) | 325 (13.7) | 901 (23.3) | |
| Other | 2889 (11.2) | 246 (10.4) | 424 (10.9) | |
| Differentiation grade | <0.001 | |||
| 1 | 6657 (25.7) | 550 (23.2) | 606 (15.6) | |
| 2 | 10726 (41.4) | 985 (41.6) | 1611 (41.6) | |
| 3 | 7086 (27.4) | 657 (27.7) | 1281 (33.1) | |
| Unknown | 1409 (5.4) | 176 (7.4) | 375 (9.7) | |
| pT | <0.001 | |||
| T1 | 19289 (74.5) | 1730 (73.1) | 2164 (55.9) | |
| T2 | 6463 (25.0) | 631 (26.6) | 1493 (38.5) | |
| T3 | 51 (0.2) | 6 (0.3) | 216 (5.6) | |
| ypT0 | 75 (0.3) | 1 (0.0) | – | |
| pN | <0.001 | |||
| N0 | 18200 (70.3) | 1589 (67.1) | 1998 (51.6) | |
| N1 | 5944 (23.0) | 620 (26.2) | 1284 (33.2) | |
| N2 | 1045 (4.0) | 104 (4.4) | 375 (9.7) | |
| N3 | 432 (1.7) | 35 (1.5) | 183 (4.7) | |
| Unknown | 257 (1.0) | 20 (0.8) | 33 (0.9) | |
| Oestrogen receptor | <0.001 | |||
| Positive | 13508 (52.2) | 1267 (53.5) | 1803 (46.6) | |
| Negative | 2720 (10.5) | 230 (9.7) | 422 (10.9) | |
| Unknown | 9650 (37.3) | 871 (36.8) | 1648 (42.6) | |
| Progesterone receptor | <0.001 | |||
| Positive | 10836 (41.9) | 996 (42.1) | 1414 (36.5) | |
| Negative | 4874 (18.8) | 424 (17.9) | 725 (18.7) | |
| Unknown | 10168 (39.3) | 948 (40.0) | 1734 (44.8) | |
| HER2Neu receptor | <0.001 | |||
| Negative | 13282 (51.3) | 1220 (51.5) | 1647 (42.5) | |
| Positive | 1761 (6.8) | 183 (7.7) | 404 (10.4) | |
| Unknown | 10835 (41.9) | 965 (40.8) | 1822 (47.0) | |
| Systemic therapyc | <0.001 | |||
| None | 13128 (51.1) | 1114 (47.0) | 1321 (34.1) | |
| Chemotherapy only | 3173 (12.3) | 286 (12.1) | 565 (14.6) | |
| Hormonal therapy only | 4038 (15.6) | 332 (14.0) | 616 (15.9) | |
| Chemotherapy and hormonal therapy | 5449 (21.1) | 636 (26.9) | 1371 (35.4) | |
pT pathological tumor stage, pN regional lymph nodes stage
a χ 2 test
bIncludes mixed ductal and lobular tumors
cBoth neoadjuvant and adjuvant
Ipsilateral breast tumor recurrence (IBTR), disease-free survival (DFS), and overall survival (OS) rates from Kaplan–Meier analysis and adjusted hazard ratio (HR) from multivariable Cox regression analysis according to the performance of re-excision in the total cohort (n = 32119)
| IBTR | DFS | OS | |||||
|---|---|---|---|---|---|---|---|
| 5-year (%) | Adjusteda HR (95% CI) | 5-year (%) | Adjusteda HR (95% CI) | 5-year (%) | 10-year (%) | Adjusteda HR (95% CI) | |
| Primary BCS only ( | 2.1 | Reference | 89.0 | Reference | 92.7 | 82.1 | Reference |
| Primary BCS + re | 2.8 | 1.31 (1.00–1.71) | 87.7 | 1.13 (1.00–1.28) | 94.5 | 85.3 | 0.89 (0.80–1.00) |
| Primary BCS + re-excision by mastectomy ( | 2.9 | 0.89 (0.57–1.40) | 82.9 |
| 89.9 | 78.7 |
|
Italic values indicate p < 0.05
aAdjusted for: age (continuous), histology (ductal, lobular, or other), differentiation grade (1, 2, 3, or unknown), pT stage (1, 2, 3, or ypT0), pN stage (1, 2, 3, or unknown), estrogen receptor status (positive, negative, or unknown), HER2Neu receptor status (positive, negative, or unknown), use of systemic therapy (any or none), and radiotherapy (yes or no)
bAll patients had radiotherapy (100%)
cRadiotherapy was performed in 873 (22.5%) of the patients
Clinicopathological and treatment characteristics according to resection margin after primary BCS and the performance of re-excision in the subcohort (n = 10433)
| Negative margin and primary BCS only | Focally positive margin and primary BCS only | Focally positive margin and primary BCS + re-excisiona | Extensively positive margin and primary BCS + re-excisionb |
| |
|---|---|---|---|---|---|
| Total no. of patients | 7820 (75.0) | 492 (4.7) | 586 (5.6) | 1535 (14.7) | |
| Age | <0.001 | ||||
| >60 years | 2695 (34.5) | 210 (42.7) | 149 (25.4) | 374 (24.4) | |
| 51–60 years | 2346 (30.0) | 120 (24.4) | 169 (28.8) | 417 (27.2) | |
| 41–50 years | 2258 (28.9) | 145 (29.5) | 218 (37.2) | 583 (38.0) | |
| ≤40 years | 521 (6.7) | 17 (3.5) | 50 (8.4) | 161 (10.5) | |
| Histology | <0.001 | ||||
| Ductal | 6233 (79.7) | 379 (77.0) | 427 (72.9) | 1046 (68.2) | |
| Lobularc | 783 (10.0) | 69 (13.8) | 110 (18.8) | 317 (20.6) | |
| Other | 804 (10.3) | 45 (9.1) | 49 (8.4) | 172 (11.2) | |
| Differentiation grade | <0.001 | ||||
| 1 | 1766 (22.6) | 105 (21.3) | 94 (16.0) | 254 (16.5) | |
| 2 | 3114 (39.8) | 202 (41.1) | 229 (39.1) | 618 (40.3) | |
| 3 | 2440 (31.2) | 149 (30.3) | 217 (37.0) | 506 (33.0) | |
| Unknown | 500 (6.4) | 36 (7.3) | 46 (7.8) | 157 (10.2) | |
| pT | <0.001 | ||||
| T1 | 5576 (71.3) | 345 (70.1) | 347 (59.2) | 866 (56.4) | |
| T2 | 2123 (27.1) | 145 (29.5) | 227 (38.7) | 593 (38.6) | |
| T3 | 15 (0.2) | 2 (0.4) | 12 (2.0) | 76 (5.0) | |
| ypT0 | 34 (0.4) | – | – | – | |
| pN | <0.001 | ||||
| N0 | 5166 (66.1) | 316 (64.2) | 297 (50.7) | 816 (53.2) | |
| N1 | 2231 (27.4) | 117 (23.8) | 214 (36.5) | 503 (32.8) | |
| N2 | 344 (4.4) | 40 (8.1) | 47 (8.0) | 142 (9.3) | |
| N3 | 120 (1.5) | 17 (3.5) | 25 (4.3) | 61 (3.9) | |
| Unknown | 67 (0.9) | 2 (0.4) | 3 (0.5) | 13 (0.8) | |
| Oestrogen receptor | <0.001 | ||||
| Positive | 3292 (42.1) | 217 (44.1) | 245 (41.8) | 531 (34.6) | |
| Negative | 710 (9.1) | 42 (8.5) | 55 (9.4) | 124 (8.1) | |
| Unknown | 3818 (48.8) | 233 (47.4) | 286 (48.8) | 880 (57.3) | |
| Progesterone receptor | <0.001 | ||||
| Positive | 2662 (34.0) | 176 (35.8) | 182 (31.1) | 410 (26.7) | |
| Negative | 1253 (16.0) | 81 (16.5) | 103 (17.6) | 227 (14.8) | |
| Unknown | 3905 (49.9) | 235 (47.8) | 301 (51.4) | 898 (58.5) | |
| HER2Neu receptor | <0.001 | ||||
| Negative | 3890 (37.0) | 188 (38.2) | 196 (33.4) | 392 (25.5) | |
| Positive | 980 (12.5) | 68 (13.8) | 96 (16.4) | 233 (15.2) | |
| Unknown | 3950 (50.5) | 236 (48.0) | 294 (50.2) | 910 (59.3) | |
| Systemic therapyd | <0.001 | ||||
| None | 3214 (41.1) | 183 (37.2) | 179 (29.0) | 468 (30.5) | |
| Chemotherapy only | 1011 (12.9) | 53 (10.8) | 82 (14.0) | 225 (14.7) | |
| Hormonal therapy only | 1168 (14.9) | 83 (16.9) | 79 (13.5) | 180 (11.7) | |
| Chemotherapy and hormonal therapy | 2427 (31.0) | 173 (35.2) | 255 (43.5) | 662 (43.1) | |
| Radiotherapy | 7820 (100) | 492 (100) | 352 (60.1) | 786 (51.2) | <0.001 |
pT pathological tumor stage, pN regional lymph nodes stage
aRe-excision by BCS in 268 (45.7%) patients of whom all had radiotherapy (100%) and re-excision by mastectomy in 318 (54.3%) patients of whom 84 (26.4%) had radiotherapy
bRe-excision by BCS in 516 (33.7%) patients whom all had radiotherapy (100%) and re-excision by mastectomy in 1016 (66.3%) patients of whom 270 (26.5%) had radiotherapy
cIncludes mixed ductal and lobular tumors
dBoth neoadjuvant and adjuvant
Fig. 2Re-excisions according to the tumor component focally touching the inked margin. Figure only shows the patients with focally positive margins after primary BCS from the subcohort (n = 1078). Re-excision was omitted in 492 (45.6%) patients (total of blue bars) and was performed in 586 (54.4%) patients (total of orange and red bars). The frequency and type of re-excision is shown according to which component of the tumor was focally touching the inked margin
Ipsilateral breast tumor recurrence (IBTR), disease-free survival (DFS), and overall survival (OS) rates from Kaplan–Meier analysis and adjusted hazard ratio (HR) from multivariable Cox regression analysis according to resection margins after primary BCS and the performance of re-excision in the subcohort (n = 10433)
| IBTR | DFS | OS | |||||
|---|---|---|---|---|---|---|---|
| 5-year | Adjusteda HR (95% CI) | 5-year (%) | Adjusteda HR (95% CI) | 5-year (%) | 10-year (%) | Adjusteda HR (95% CI) | |
| Negative margins and primary BCS only ( | 163 (2.3%) | 0.76 (0.43–1.35) | 89.2 | 0.81 (0.63–1.04) | 93.1 | 82.9% | 1.07 (0.85–1.34) |
| Focally positive margins | |||||||
| Primary BCS only ( | 13 (2.9%) | Reference | 86.0 | Reference | 92.7 | 81.1 | Reference |
| Primary BCS + re-excision ( | 6 (1.1%) |
| 87.1 | 0.83 (0.59–1.17) | 92.1 | 82.1 | 1.17 (0.87–1.59) |
| By BCS ( | 3 (1.3%) | 0.39 (0.11–1.38) | 90.7 | 0.66 (0.42–1.06) | 94.8 | 86.0 | 1.01 (0.68–1.49) |
| By mastectomy ( | 3 (1.0%) |
| 84.0 | 0.98 (0.66–1.47) | 89.9 | 78.7 | 1.34 (0.93–1.91) |
| Extensively positive margins and primary BCS + re-excision ( | 40 (2.9%) | 0.75 (0.37–1.51) | 84.7 | 0.97 (0.72–1.31) | 91.8 | 81.1 | 1.22 (0.94–1.59) |
Italic values indicate p < 0.05
aAdjusted for: age (continuous), histology (ductal, lobular, or other), differentiation grade (1, 2, 3, or unknown), pT stage (1, 2, 3, or ypT0), pN stage (1, 2, 3, or unknown), estrogen receptor status (positive, negative, or unknown), HER2Neu receptor status (positive, negative, or unknown), use of systemic therapy (any or none), and radiotherapy (yes or no). Complete table can be found in the Online Resource 1, Table 1
bRadiotherapy was performed in all patients with BCS (100%)
cRadiotherapy was performed in 352 (60.1%) of the patients since all 268 patients with re-excision by BCS (100%) and 84 (26.4%) of the patients with re-excision by mastectomy had radiotherapy
dRadiotherapy was performed in 84 (26.4%) patients
eAdjuvant radiotherapy was performed in 786 (51.2%) patients since all 516 patients with re-excision by BCS (100%) and 270 (26.5%) of the patients with re-excision by mastectomy had radiotherapy