In our patient collective of 2095 patients with conventional axillary dissection, the nodal status was node-negative (N -) in 1270 (61%) and node-positive (N +) in 825 patients (39%).
1. Frequency of surgery for N + in level I, II, III and interpectoral
In order to analyze the correct lymph node distribution, it was necessary to know the operation frequency of the specific nodal stations. In patients with affected lymph nodes, the lymphadenectomy was performed in level I in 100%, in level II in 99%, in level III in 95% and in interpectoral in 71% of all patients.
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Number of removed and affected lymph nodes related to the surgery in the corresponding level with N +
Table 1
Number of removed and affected lymph nodes related to the surgery in the corresponding level with N +
| level I | level II | level III | interpectoral | total number |
surgery | 825 | 816 | 785 | 582 | 825 |
N+ | 814 | 237 | 145 | 56 | |
% | 98.7 | 29.0 | 18.5 | 9.6 | |
removed LN, mean | 16.5 | 6.4 | 2.7 | 1.3 | 26.5 |
SD | 5.6 | 3.6 | 2 | 1.4 | 8.9 |
min - max | 3 - 49 | 0 - 23 | 0 - 18 | 0 - 9 | 3 - 77 |
affected LN, mean | 4 | 1,1 | 0,4 | 0,2 | 5.6 |
SD | 4.6 | 2.4 | 1.2 | 0.6 | 7.6 |
min - max | 0 - 30 | 0 - 19 | 0 - 12 | 0 - 7 | 1 - 51 |
SD: standard deviation, LN: lymph nodes |
Table 1 shows that with positive nodal stage, level I was affected in 98.7%. Skip metastases were found in 11 patients, meaning other stations than level I of the lymphatic drainage were affected. Level II was affected in 29%, level III in 18.5% and interpectoral in 9.6%. If the nodal stage was positive, a mean of a total of 26.5 lymph nodes were removed (range: 3 - 77), including 16.5 lymph nodes in level I, 6.4 lymph nodes in level II, 2.7 lymph nodes in level III and 1.3 in interpectoral. The mean was 5.6 lymph node metastases (range: 1 - 51).
3. Number of affected lymph nodes in 825 cases of nodal positive patients
Table 2
Number of affected lymph nodes in 825 cases of nodal positive patients
| frequency at N + |
Number of affected lymph nodes | n | % |
1 LN | 295 | 35.8 |
2 LN | 117 | 14.2 |
3 LN | 90 | 10.9 |
4 LN | 51 | 6.2 |
5 LN | 47 | 5.7 |
6 LN | 24 | 2.9 |
7 LN | 15 | 1.8 |
8 LN | 29 | 3.5 |
9 LN | 15 | 1.8 |
≥ 10 LN | 142 | 17.2 |
1 - 3 LN | 502 | 60.9 |
4 - 9 LN | 181 | 21.9 |
total number | 825 | 100 |
LN: lymph nodes, N+: nodal positive, n: number of patients |
Table 2 shows that of a total of 825 patients with positive node status, 295 patients (35.8%) had only one lymph node metastasis and 530 patients (64.2%) had more than one. 60.9% of the patients had 1 to 3 lymph node metastases and in 21.9% 4 to 9 lymph nodes were affected. 17.2% had more than 9 lymph node metastases. The mean was 5.6 lymph node metastases.
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Frequency of axillary involvement with 0, 1, 2, 3 or more affected lymph nodes in level I.
If there were no lymph node metastases in level I but an involvement of higher lymph nodes, the distribution of lymph node metastases in a total of 825 patients with positive node status shows that level I was not affected in 11 patients (1.33%). Lymph node metastases were found in level II in 3 patients, in level III in 4 patients and in interpectoral in 4 patients.
Table 3
Frequency of axillary involvement with 0, 1, 2, 3 or more affected lymph nodes in level I.
Affected node stations | 1 lymph node metastasis in Level I | 2 lymph node metastases in Level I | 3 lymph node metastases in Level I | ≥4 lymph node metastases in level I |
| LA | n | % | LA | n | % | LA | n | % | LA | n | % |
level I | 312 | 312 | 100 | 120 | 120 | 100 | 92 | 92 | 100 | 290 | 290 | 100 |
level II, III or ip | | 27 | 8.7 | | 21 | 17.5 | | 22 | 23.9 | | 199 | 68.6 |
level II | 308 | 18 | 5.8 | 120 | 13 | 10.8 | 90 | 17 | 18.9 | 287 | 186 | 64.8 |
level III | 300 | 9 | 3.0 | 117 | 4 | 3.4 | 86 | 8 | 9.3 | 271 | 120 | 44.3 |
ip | 221 | 6 | 2.7 | 92 | 5 | 5.4 | 64 | 5 | 7.8 | 196 | 36 | 18.4 |
LA: lymphadenectomy; n: number of patients with lymph node metastases; %: percentage of affected lymph node station in relation to the frequency of surgery; ip: interpectoral
Table 3 shows the distribution of lymph node metastasis in patients with 1, 2, 3 or more lymph node metastases in level I. Of 312 patients with 1 affected lymph node in level I, a total of 27 of the patients (8.7%) had lymph node involvement in higher lymphatic stations. In 6 patients, several lymph node stations were affected. In relation to the frequency of surgery in the higher lymphatic stations, this corresponds to a value of 5.8% for level II, 3,0% for level III and 2.7% for interpectoral. Of 120 patients with 2 affected lymph nodes in level I, a total of 21 (17.5%) of the patients had lymph node involvement in higher lymphatic stations. Several lymph node stations were affected in 1 patient. In relation to the frequency of surgery in the higher lymphatic stations, this corresponds to a value of 10.8% for level II, 3.4% for level III and 5.4% for interpectoral.
Of 92 patients with 3 affected lymph nodes in level I, a total of 22 (23.9%) of the patients had lymph node involvement in higher lymphatic stations. In 8 patients, several lymph node stations were affected. In relation to the frequency of surgery in the higher lymphatic stations, this corresponds to a value of 18.9% for level II, 9.3% for level III and 7.8% for interpectoral.
Of 290 patients with ≥4 affected lymph nodes in level I, 199 (68.6%) of the patients had lymph node involvement in higher lymphatic stations. In 143 patients, several lymph node stations were affected. In relation to the frequency of surgery in the higher lymphatic stations, this corresponds to a value of 64.8% for level II, 44.3% for level III and 18.4% for the interpectoral.
(A detailed table with more information is available upon request.)
5. Number of affected lymph nodes and nodal status
Table 4
Number of affected lymph nodes and nodal status
Number of total affected lymph nodes | Number of patients | N1 | N2 | N3 |
n | n | n | n | n | % |
1 | 295 | 291 | 0 | 4 | 1.4 |
2 | 117 | 116 | 0 | 1 | 0.9 |
3 | 90 | 84 | 0 | 6 | 6.7 |
4 - 9 | 181 | 0 | 164 | 17 | 9.4 |
total number | 683 | 491 | 164 | 28 | 4.1 |
≥10 | 142 | 0 | 0 | 142 | 100 |
N: nodal status N1 – 3 |
Table 4 shows that of a total of 683 patients with lymph node involvement of <10 lymph nodes, who could not be assigned to stage N3 due to the number of affected lymph nodes, 28 of these patients (4.1%) had stage N3.
6. Influencing variables for lymph node metastases in level III
6.1 Chi-square contingency test
Table 5
Influencing variables for lymph node metastases in level III
Category | Lymph node metastasis in Level III | p | Chi² |
Age | | ns | |
< 53Jahre | 6.8% (30/440) | | |
53 bis 62 Jahre | 5.9% (23/390) | | |
63 bis 71 Jahre | 8.4% (36/430) | | |
> 71 Jahre | 7.6% (30/395) | | |
BMI | | ns | |
≤ 25 | 5.4% (31/576) | | |
> 25 ≤ 30 | 6.0% (33/552) | | |
30 bis 34,9 | 9.3% (25/268) | | |
≥ 35 | 7.9% (8/101) | | |
inside quadrant * | | 0.036 | 4.382 |
no | 8.2% (85/1034) | | |
yes | 5.5% (34/621) | | |
central quadrant *** | | 0.001 | 10.675 |
no | 6.6% (102/1540) | | |
yes | 14.8% (17/115) | | |
tumor stage *** | | < 0.001 | 61.551 |
T1 | 4.4% (46/1047) | | |
T2 | 9.7% (50/513) | | |
T3 | 21.7% (13/47) | | |
T4 | 21.7% (10/46) | | |
tumor size *** | | < 0.001 | 32.316 |
≤ 10mm | 2% (5/252) | | |
11 ≤ 20mm | 5.8% (33/570) | | |
21≤ 35mm | 9.7% (35/361) | | |
> 35mm | 16.9% (20/118) | | |
Grading *** | | < 0.001 | 17.269 |
G1 | 2.9% (3/102) | | |
G2 | 5.8% (62/1069) | | |
G3 | 11.2% (54/484) | | |
Lymphangiosis *** | | < 0.001 | 111.938 |
no | 2.0% (12/612) | | |
yes | 23.4% (67/286) | | |
Hemangiosis *** | | < 0.001 | 132.990 |
no | 4.4% (34/768) | | |
yes | 41.9% (31/74) | | |
Number of affected lymph nodes in level I *** | | < 0.001 | 515.974 |
0 - 3 | 1.3% (19/1421) | | |
> 3 | 42.7% (100/234) | | |
hormone receptor | | ns | |
ER and PR negative | 7.7% (14/181) | | |
ER or PR positive | 7.1% (105/1474) | | |
Her2 | | ns | |
negative | 7.2% (106/1472) | | |
positive | 7.1% (12/183) | | |
uPA | | ns | |
negative | 8.9% (65/729) | | |
positive | 6.8% (841/599) | | |
PAI-1 | | ns | |
negative | 8.2% (57/698) | | |
positive | 7.8% (50/639) | | |
proliferation (Ki67/MIB) | | ns | |
not increased (< 30/50) | 6.9% (73/1064) | | |
increased (≥ 30/50) | 7.8% (46/591) | | |
* = p ≤ 0.05; **= p ≤ 0.01; ***= p ≤ 0.001; ns = not significant |
Table 5 shows that in the univariate chi-square analysis according to Pearson (uncorrected), age, BMI and molecular biological factors (hormone receptor status, Her2 status) were not found to be significant for an association with lymph node metastases in level III. The proliferation markers (Ki67 / MIB) or invasion markers (uPA / PAI-1) were also not significant. In contrast, the tumor stage (T1-T4), tumor size, grading, lymphangiosis, hemangiosis and the number of affected lymph nodes in level I (≤3 /> 3) were found to be highly significant. The location in the inner or central quadrant was also significant for lymph node metastases in level III.
6.1 Discriminant analysis
A step-by-step discriminant analysis was performed with the significant variables from the chi-square contingency test. The group differences were found to be significant in the discriminant analysis (Wilks-Lambda .587, Chi2 = 380.489, p = .000). The most important prognostic factors were the number of positive lymph nodes in level I (≤ 3 /> 3) (F= 437.845, p = .000), hemangiosis (F= 247.728, p= .000) and lymphangiosis (F= 167.368, p= .000).
The classification results show that 91.9% (730/794) of the originally grouped cases were correctly classified. In particular, the negative predictive value was at 85.3% (677/794). However, the positive predictive value was 6.7% (53/794).
7. Axillary relapse
Table 6
Axillary relapse | Nodal stage N0 n =1270 | Nodal stage N+ n = 825 | Total number n = 2095 |
| n | % | n | % | n | % |
Axillary relapse only first event | 3 | 0.24 | 4 | 0.49 | 7 | 0.33 |
Axillary relapse AND local breast relapse first event | 2 | 0.16 | 1 | 0.12 | 3 | 0.14 |
Axillary relapse total | 5 | 0.39 | 5 | 0.61 | 10 | 0.47 |
Axillary relapse AND later distant metastasis | 2 | 0.16 | 2 | 0.24 | 4 | 0.19 |
Table 6 shows the number of axillary relapses as first event, either alone or in combination with a local relapse. It is also shown how often a distant metastasis occurs later.