Introduction: As applied to early breast cancer (BC) patients, sentinel node biopsy (SNB) has undergone major changes over the years, especially concerning the widening of indication criteria or skipping systematic axillary lymph node dissection (ALND) after a positive SN. We aimed to ascertain whether a strict versus a more liberal use of SNB resulted in different clinical outcomes in our clinical experience. Methods: We studied consecutive BC patients undergoing SNB between January 1, 2000, and March 31, 2020. There were 1,587 patients and 1,634 SNB procedures. Cases were divided into two study groups: the “strict” SNB group (unifocal tumors up to 35 mm in which ALND was always performed for a positive SN, amounting to 1,183 SNBs), and the “liberal” SNB group (extended tumor size up to selected T3 cases, as well as multifocal or bilateral disease, and patients with previous contralateral BC, not always followed by ALND after a positive SN, amounting to 451 SNBs). Patients were closely followed up to the end of the study. Results: Clinico-pathological variables were strikingly different between study groups, with the liberal group showing a higher risk profile. Cox regression analysis for disease recurrence did not show significant differences in axillary, lymph node, or locoregional recurrence rates or distant relapse. There were no differences in survival between groups. Conclusion: It seems reasonable to adopt the liberal SNB approach, as the goal of surgical management in early BC patients must be attaining optimal locoregional disease control, no matter the differences in distant metastatic spread rates across different BC risk profiles.

Sentinel node biopsy (SNB) is the first-choice axillary staging procedure in early-stage breast cancer (BC) patients with a clinically negative axilla [1‒3]. SNB has undergone relevant changes during the first two decades of its implementation, especially concerning criteria used for SNB indication or the sparing of systematic axillary lymph node dissection (ALND) after a positive SN [4, 5]. As for indication criteria, SNB evolved from a strict tumor size upper limit of 2 cm to encompass all T1-T2 patients. A similar trend was also seen from solitary to multicentric tumors, unilateral to bilateral BC, or even using SNB in the neoadjuvant setting, among other changes [6].

As for compulsory ALND after a positive SNB, the striking pathology finding that most of the axillary tumor burden relates to the SN itself led to the ACOSOG Z0011 [7] proposal of avoiding axillary dissection in patients with up to two positive SNs [4]. However, sparing completion of ALND may still be controversial because, as a confounding factor, enhanced axillary radiation therapy is used as a backup armamentarium, with similar morbidity [4, 5, 7, 8]. As an alternative, predictive models of residual axillary disease [9‒11] such as the Tenon score were proposed to avoid AD [12], as in our practice. However, the Z011 approach has finally gained full acceptance, even though we must be aware that residual axillary disease may still be left unremoved in some BC patients.

Of note, such evolving criteria for SNB practice have run in parallel with significant changes in the clinical presentation of BC itself. These have resulted in an ever-improving patient prognosis associated with diagnosis at an earlier stage of the condition [13‒15]. Therefore, the strict indication criteria and the exhaustive management of the axilla might not be as critical now as they were during the first stages of SNB, more than 20 years ago. We believe that most clinical centers dealing with BC have adopted such changes in SNB practice over the years. With all this in mind, we set out to investigate whether a strict versus a more liberal use of SNB resulted in different clinical outcomes, as measured by axillary recurrence, distant metastases, or survival in a cohort of BC patients that received SNB and were followed-up for a considerable time lapse.

Patient Inclusion/Exclusion

From our Breast Unit Database, we selected female patients with invasive BC receiving an SNB between January 1, 2000, and March 31, 2020. We excluded patients with ductal carcinoma in situ and patients from the SNB validation period. We also excluded patients accrued for some clinical trials associated with compulsory ALND, and for that matter, any patient receiving ALND after a negative SNB due to tumor factors such as size or multifocality until a more liberal policy was considered. Written informed consent was obtained for all invasive procedures and surgery, as well as for inclusion of patient data in the database. The present study was approved by our Research Ethics Committee on January 20, 2022, with the number P/22-012.

Our database includes the usual baseline and follow-up variables, such as age, surgical pathology results, systemic and radiation adjuvant therapy regimes, local recurrence, distant recurrence, and death, among many others. Our database has been seamlessly kept updated daily to the present. Initially, SNB was performed only in BC patients with solitary tumors up to 35 mm in size with clinically and US scan-negative axillary nodes. Further SNB indications were progressively introduced later on, prompting the following definitions.

Definitions

The “strict” SNB group included patients with a single invasive tumor of up to 35 mm and a clinically negative axilla. ALND was performed after a positive SN.

The “liberal” SNB group included patients with widened indications resulting from our evolving clinical routine, such as some locally advanced (T3) tumors, multifocal or bilateral disease, patients with previous contralateral BC, and pre- or post-neoadjuvant chemotherapy SNB procedures or repeat SNB for tumor recurrence.

Evolving SNB Practice and Study Groups

Initially, we implemented the SNB as a substitute for ALND in early BC patients with a single invasive tumor of up to 35 mm and a clinically negative axilla. The technique for SNB has been described elsewhere [9] and is based on the intra-peritumoral injection of 99m-technetium nanocolloids, preoperative lymphoscintigraphy, and intraoperative detection of the SN using a gamma probe.

From 2003 on, we have been using preoperative axillary US scans as a screening procedure for SNB. From January 2014 on, indications for SNB were extended to include all patients with T2 invasive tumors and multifocal tumors. Also, in early 2014, we applied a modified Tenon score for patients with positive SNs to forgo ALND [8]. Because of an excess of negative ALNDs, from June 2014 on, we incrementally applied the Z0011 approach for patients with one positive SN.

Accordingly, we devised two study groups as previously stated. The first was the “strict” SNB group. Initially, strict patients with SN micrometastases were also subjected to ALND, until 2010, when the results of our clinical trial on skipping ALND in SN with micrometastases were published [16]. The second group was the “liberal” SNB group. Not every patient with macrometastatic-positive SNs in this group was subjected to ALND because we often applied the Tenon score or the Z0011 criteria.

Adjuvant Therapy

Patients were treated according to the “state-of-the-art” clinical protocol of our Breast Unit Database, based on both national and international guidelines. Chemotherapy regimens based on anthracyclines and taxanes, or hormone therapy regimens with tamoxifen or aromatase inhibitors were most commonly used. From 2003 on, trastuzumab was given to Her2+ patients. Adjuvant radiation therapy was based on CT bidimensional planning until 2008 when tridimensional planning was implemented.

Statistical Analysis

We used qualitative or discrete variables expressed as their number and percentage. For univariate analysis, variable comparisons were achieved using the χ2 test or Fisher’s exact test. Statistical significance was set at a p value of <0.05, with a two-tail approach. Rates of axillary and locoregional recurrence were calculated over the SNB procedures, whereas rates of metastases and mortality were calculated over the patient numbers. Taking strict and liberal indications for SNB together, the Cox regression was used for disease recurrence analysis. The Kaplan-Meier test and the log-rank test were used for survival analysis. All statistical analyses were performed using IBM SPSS 25.0.3. statistical package (Armonk, NY, USA).

Over the 20-year period, 2,574 patients were treated for invasive BC, 1,586 of whom received SNB (61.7%). Because some patients presented with synchronous (58) or metachronous (48) bilateral tumors (not all of them receiving SNB), the total number of SNB cases was 1,634. Of these, 1.183 belong to the strict SNB group (72.4%) and 451 to the liberal SNB group (27.6%). Patients in the strict SNB group were followed up for a mean of 86 ± 56 months (SD) (range 2–253 months), while liberal SNB patients were followed up for a mean time of 80.7 ± 67.9 months (SD) (range 2–245 months).

Figure 1 displays the timeline of changes in the clinical management of patients undergoing SNB in our practice. It can be seen that those changes started in 2009 and peaked during the 2013–2015 period. During the 2015–2019 period, the liberal group of patients accounted for more than 50%. Before 2003, no patients with Her2+ tumors received trastuzumab. Triple therapy with trastuzumab + pertuzumab + taxanes was introduced for all candidate patients, irrespective of their group.

Fig. 1.

Time spread of “strict” versus “liberal” SNB procedures over the 20-year period of our SNB practice.

Fig. 1.

Time spread of “strict” versus “liberal” SNB procedures over the 20-year period of our SNB practice.

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Table 1 shows comparative features of both study groups. All considered variables were significantly different among groups. Patients in the liberal group showed increased rates of T2-T3 tumors, Ki67 over 20%, stages II and III, non-luminal A phenotypes, lobular and mixed tumor histologies, age under 50, and diagnosis outside the mass-screening program. Patients in the strict group showed higher rates of lymphovascular invasion, although significance was lost when missing cases were discarded, and histologic grade III, Patients in the liberal group showed higher rates of both macro and micrometastases, as well as higher axillary tumor burden. There were no differences concerning extracapsular extension. Patients in the strict group significantly received more adjuvant radiation therapy, probably as a result of fewer mastectomy procedures. As could be expected from their clinical features, patients in the liberal group significantly received more adjuvant chemotherapy. However, the overall combined adjuvant therapy was not significantly different (Table 2).

Table 1.

Baseline characteristics of patients and breast tumors according to the study groups: univariate analysis

Strict SNB-1,183, N (%)Liberal SNB-451, N (%)p value
Age   0.000 
 <50 252 (21.3) 146 (32.4)  
 50–69 707 (59.8) 219 (48.5)  
 ≥70 224 (18.9) 86 (19.1)  
T type   0.000 
 Ductal Ca 1,112 (94) 379 (84)  
 Lobular Ca 61 (5.2) 59 (13.1)  
 Mixt type 10 (0.8) 13 (2.9)  
T size   0.000 
 T1 911 (77) 284 (63)  
 T2 272 (23) 147 (32.6)  
 T3 20 (4.4)  
Lymphovascular invasion   0.009 
 No 864 (73) 320 (71) 0.513 
 Yes 293 (24.8) 108 (23.9) 
 Missing 26 (2.2) 23 (5.1)  
BC diagnosis   0.000 
 Clinical care 625 (52.8) 305 (67.6)  
 Population mass screening 558 (47.2) 146 (32.4)  
Histological grade   0.004 
 1 375 (31.7) 110 (24.4) 0.011 
 2 537 (45.4) 234 (51.9) 
 3 255 (21.6) 94 (20.8) 
 Missing 16 (1.3) 13 (2.9)  
Ki67   0.008 
 <20 330 (27.9) 118 (26.2)  
 ≥20 378 (32) 191 (42.4)  
 Missing 475 (40.1) 142 (31.4)  
Surgical procedure   0.000 
 Conservative 1,072 (90.6) 291 (64.5)  
 Mastectomy 111 (9.4) 160 (35.5)  
Stage   0.000 
 I 741 (62.6) 224 (49.6)  
 IIA 340 (28.8) 132 (29.3)  
 IIB 75 (6.3) 69 (15.3)  
 III(A + B + C) 27 (2.3) 26 (5.8)  
Phenotype   0.030 
 Luminal A 517 (43.7) 170 (37.7)  
 Luminal B her2- 424 (35.8) 160 (35.5)  
 Luminal B her2+ 96 (8.1) 49 (10.9)  
 Her2 pure 33 (2.8) 16 (3.5)  
 Triple negative 112 (9.5) 53 (11.7)  
 Missing 1 (0.1) 3 (0.7)  
Strict SNB-1,183, N (%)Liberal SNB-451, N (%)p value
Age   0.000 
 <50 252 (21.3) 146 (32.4)  
 50–69 707 (59.8) 219 (48.5)  
 ≥70 224 (18.9) 86 (19.1)  
T type   0.000 
 Ductal Ca 1,112 (94) 379 (84)  
 Lobular Ca 61 (5.2) 59 (13.1)  
 Mixt type 10 (0.8) 13 (2.9)  
T size   0.000 
 T1 911 (77) 284 (63)  
 T2 272 (23) 147 (32.6)  
 T3 20 (4.4)  
Lymphovascular invasion   0.009 
 No 864 (73) 320 (71) 0.513 
 Yes 293 (24.8) 108 (23.9) 
 Missing 26 (2.2) 23 (5.1)  
BC diagnosis   0.000 
 Clinical care 625 (52.8) 305 (67.6)  
 Population mass screening 558 (47.2) 146 (32.4)  
Histological grade   0.004 
 1 375 (31.7) 110 (24.4) 0.011 
 2 537 (45.4) 234 (51.9) 
 3 255 (21.6) 94 (20.8) 
 Missing 16 (1.3) 13 (2.9)  
Ki67   0.008 
 <20 330 (27.9) 118 (26.2)  
 ≥20 378 (32) 191 (42.4)  
 Missing 475 (40.1) 142 (31.4)  
Surgical procedure   0.000 
 Conservative 1,072 (90.6) 291 (64.5)  
 Mastectomy 111 (9.4) 160 (35.5)  
Stage   0.000 
 I 741 (62.6) 224 (49.6)  
 IIA 340 (28.8) 132 (29.3)  
 IIB 75 (6.3) 69 (15.3)  
 III(A + B + C) 27 (2.3) 26 (5.8)  
Phenotype   0.030 
 Luminal A 517 (43.7) 170 (37.7)  
 Luminal B her2- 424 (35.8) 160 (35.5)  
 Luminal B her2+ 96 (8.1) 49 (10.9)  
 Her2 pure 33 (2.8) 16 (3.5)  
 Triple negative 112 (9.5) 53 (11.7)  
 Missing 1 (0.1) 3 (0.7)  
Table 2.

Surgical pathology, adjuvant therapy, and specific mortality characteristics according to the study group. Univariate analysis

Strict SNB-1183, N (%)Liberal SNB-451, N (%)p value
Ax LN dissection   0.004 
 No 986 (83.3) 349 (77.4)  
 Yes 197 (16.7) 102 (22.6)  
SN pathology   0.000 
 Negative SN 902 (76.2) 293 (65)  
 Micrometastasis 182 (15.4) 109 (24.2)  
 Macrometastasis 99 (8.4) 49 (10.8)  
SNB tumor burden   0.000 
 0 positive SN 902 (76.2) 293 (65)  
 1 positive SN 231 (19.5) 126 (27.9)  
 2 positive SN 39 (3.3) 27 (6)  
 ≥3 positive SN 11 (1) 5 (1.1)  
LN tumor burden after axillary dissection   0.000 
 0 positive LN 902 (76.2) 293 (65)  
 1 positive LN 199 (16.8) 109 (24.1)  
 2 positive LN 41 (3.5) 22 (4.9)  
 ≥3 positive LN 41 (3.5) 27 (6)  
Extracapsular extension   0.189 
 No ECE 1,129 (95.4) 425 (94.2)  
 ECE 54 (4.6) 26 (5.8)  
Adjuvant radiation therapy   0.000 
 Not 85 (7.2) 123 (27.3)  
 Yes 1,098 (92.8) 328 (72.7)  
Adjuvant chemotherapy*   0.000 
 Not 645 (54.5) 153 (38)  
 Yes 538 (45.5) 250 (62)  
Hormone therapy*   0.449 
 Not 148 (12.5) 52 (12.9)  
 Yes 1,035 (87.5) 351 (87.1)  
Adjuvant therapy*   0.185 
 Not 38 (3.2) 8 (2)  
 Yes 1,145 (96.8) 395 (98)  
Specific mortality*   0.480 
 Alive 1,150 (97.2) 391(97)  
 Dead from BC 33 (2.8) 12 (3)  
Strict SNB-1183, N (%)Liberal SNB-451, N (%)p value
Ax LN dissection   0.004 
 No 986 (83.3) 349 (77.4)  
 Yes 197 (16.7) 102 (22.6)  
SN pathology   0.000 
 Negative SN 902 (76.2) 293 (65)  
 Micrometastasis 182 (15.4) 109 (24.2)  
 Macrometastasis 99 (8.4) 49 (10.8)  
SNB tumor burden   0.000 
 0 positive SN 902 (76.2) 293 (65)  
 1 positive SN 231 (19.5) 126 (27.9)  
 2 positive SN 39 (3.3) 27 (6)  
 ≥3 positive SN 11 (1) 5 (1.1)  
LN tumor burden after axillary dissection   0.000 
 0 positive LN 902 (76.2) 293 (65)  
 1 positive LN 199 (16.8) 109 (24.1)  
 2 positive LN 41 (3.5) 22 (4.9)  
 ≥3 positive LN 41 (3.5) 27 (6)  
Extracapsular extension   0.189 
 No ECE 1,129 (95.4) 425 (94.2)  
 ECE 54 (4.6) 26 (5.8)  
Adjuvant radiation therapy   0.000 
 Not 85 (7.2) 123 (27.3)  
 Yes 1,098 (92.8) 328 (72.7)  
Adjuvant chemotherapy*   0.000 
 Not 645 (54.5) 153 (38)  
 Yes 538 (45.5) 250 (62)  
Hormone therapy*   0.449 
 Not 148 (12.5) 52 (12.9)  
 Yes 1,035 (87.5) 351 (87.1)  
Adjuvant therapy*   0.185 
 Not 38 (3.2) 8 (2)  
 Yes 1,145 (96.8) 395 (98)  
Specific mortality*   0.480 
 Alive 1,150 (97.2) 391(97)  
 Dead from BC 33 (2.8) 12 (3)  

*Per patient calculation.

To recap, looking at Tables 1 and 2 it can be inferred that patients in the liberal SNB group tended to be younger and less prone to be diagnosed at the mass-screening program than were strict SNB patients. They also tended to show higher tumor size and tumor grade and were more often bilateral and of lobular histologic type, have more macrometastatic SNs, with higher axillary tumor burden and higher disease stage. Also, they were more prone to receiving mastectomy and ALND. Finally, although both groups were similarly treated with adjuvant therapy overall, liberal SNB patients did receive a lower rate of adjuvant radiation therapy and a higher rate of adjuvant chemotherapy.

Table 3 shows specific indications for SNB in the liberal group. Multifocality was the most common of them. Also, in Table 3, event rates of disease recurrence and distant metastases can be seen. Cox regression (not included in Table 3) did not reveal significant differences when considering rates of disease recurrence according to SNB-specific indications: p values from 0.604 to 0.961 for axillary recurrence, p values from 0.360 to 0.986, for lymph-node recurrence, and p values from 0.271 to 0.984 for metastases. Although the two groups had very different profiles, no significant differences were observed in the rates of axillary recurrence (1.3% vs. 0.9%), which were indeed very low, nor in the rates of lymph-nodal metastases (1.8% vs. 2%), overall recurrence (4.2% vs. 4.9%), overall survival, overall distant metastases (4.1% vs. 6%) or BC (2.8% vs. 3%).

Table 3.

Locoregional recurrence and metastases rates according to SNB clinical use

Total SNB, N (%)*Axillary recurrence, N (%)Lymp-node recurrence, N (%)Lymphnode metastases, N (%)Overall metastases, N (%)
Strict SNB use 1,183 (72.4) 17 (0.1) 39 (2.4) 27 (1.6) 68 (4.2) 
Liberal SNB use 
 Synchronous bilateral tumors 96 (5.9) 5 (0.3) 
 Previous contralateral BC 58 (3.5) 3 (0.2) 3 (0.2) 6 (0.4) 
 Multifocal tumors 205 (12.5) 2 (0.1) 4 (0.3) 3 (0.2) 7 (0.4) 
 Multicentric tumors 77 (4.7) 1 (0.1) 1 (0.1) 3 (0.2) 
 Tumor size over 35 mm 71 (4.3) 2 (0.1) 4 (0.3) 2 (0.1) 5 (0.3) 
 Pre-chemo SNB 24 (1.5) 
 Post-chemo SNB 27 (1.6) 1 (0.1) 2 (0.1) 2 (0.1) 2 (0.1) 
 Repeat SNB 3 (0.2) 
Total SNB, N (%)*Axillary recurrence, N (%)Lymp-node recurrence, N (%)Lymphnode metastases, N (%)Overall metastases, N (%)
Strict SNB use 1,183 (72.4) 17 (0.1) 39 (2.4) 27 (1.6) 68 (4.2) 
Liberal SNB use 
 Synchronous bilateral tumors 96 (5.9) 5 (0.3) 
 Previous contralateral BC 58 (3.5) 3 (0.2) 3 (0.2) 6 (0.4) 
 Multifocal tumors 205 (12.5) 2 (0.1) 4 (0.3) 3 (0.2) 7 (0.4) 
 Multicentric tumors 77 (4.7) 1 (0.1) 1 (0.1) 3 (0.2) 
 Tumor size over 35 mm 71 (4.3) 2 (0.1) 4 (0.3) 2 (0.1) 5 (0.3) 
 Pre-chemo SNB 24 (1.5) 
 Post-chemo SNB 27 (1.6) 1 (0.1) 2 (0.1) 2 (0.1) 2 (0.1) 
 Repeat SNB 3 (0.2) 

*The percentage of indications exceeds 100% because two or more of them were present in several cases.

Again, Cox regression analysis did not reveal any significant association of study group and event rates, except for overall metastases rates that were significantly higher in the liberal group. Hazard ratio values and corresponding 95% CI are shown in Table 4. Indeed, all patients had cN0M0 early BC. Furthermore, neither Kaplan-Meyer nor log-rank analysis showed significant differences between groups in terms of axillary recurrence, lymph node recurrence, lymph node metastases, and distant metastases (Fig. 2a–d).

Table 4.

Disease events at follow-up according to the study group, together with Cox regression analysis

Strict SNB 1183, N (%)Liberal SNB 451, N (%)Cox regression
Bp valuehazard ratio95% CI for hazard ratio
lowerupper
Axillary recurrence 15/(1.3) 4 (0.9) −1.231 0.107 0.292 0.065 1.307 
Locoregional LN recurrence 18/(1.5) 7 (1.6) 1.216 0.057 3.373 0.965 11.788 
Total recurrence 50/(4.2) 22 (4.9) 0.209 0.445 1.232 0.721 2.106 
Overall metastases 49/(4.1) 24 (6) 1.063 <0.000 2.896 1.750 4.791 
Lymph-node metastases 21/(1.8) 8 (2) −0.477 0.271 0.621 0.266 1.450 
Survival 1,150 (97.2) 391/403 (97) −0.444 0.131 0.131 0.361 1.141 
Strict SNB 1183, N (%)Liberal SNB 451, N (%)Cox regression
Bp valuehazard ratio95% CI for hazard ratio
lowerupper
Axillary recurrence 15/(1.3) 4 (0.9) −1.231 0.107 0.292 0.065 1.307 
Locoregional LN recurrence 18/(1.5) 7 (1.6) 1.216 0.057 3.373 0.965 11.788 
Total recurrence 50/(4.2) 22 (4.9) 0.209 0.445 1.232 0.721 2.106 
Overall metastases 49/(4.1) 24 (6) 1.063 <0.000 2.896 1.750 4.791 
Lymph-node metastases 21/(1.8) 8 (2) −0.477 0.271 0.621 0.266 1.450 
Survival 1,150 (97.2) 391/403 (97) −0.444 0.131 0.131 0.361 1.141 
Fig. 2.

a Axillary lymph node relapse. b Lymph node relapse. c Lymph node metastases. d Overall metastases.

Fig. 2.

a Axillary lymph node relapse. b Lymph node relapse. c Lymph node metastases. d Overall metastases.

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In general, an ever-increasing “liberal” policy for SNB practice has been accepted over the years and this has translated into several consensus statements and guidelines. The SNB might still be considered a matter of debate for specific subgroups of BC patients. In our experience, the first additional indication for SNB was in patients with multifocal/multicentric tumors, for which we used separate lymphatic tracer injections. The practical results were similar to those of patients with a single breast tumor, as reported by others [17, 18]. Compared to other reports (17–20), our timeline of SNB changes was somewhat sluggish, although nonetheless remarkable from early on (Fig. 1). Adjuvant therapy evolved according to well-established tumor features, irrespective of the SNB practice. Also, both gene expression testing and new chemotherapy regimes were implemented independently from the surgical procedures.

Our practice paralleled literature reports involving SNB in patients with T3 tumors and clinically negative axilla [19, 20], also showing similar results to those patients with T1-T2 tumors. Data are scant regarding repeat SNB after a previous SN procedure, but in our analysis, we believe it did not have a great bearing for group comparison, a fact that has also been reported in another study with 46 months of follow-up [21]. Others, however, seem more reluctant to repeat SNB given the lower SN detection rates, especially after a complete ALND [22, 23]. We think that SNB in the neoadjuvant setting has proved to be accurate and safe in patients with clinically negative axilla, as already pointed out [6, 24].

In our clinical practice, the more liberal use of SNB did not translate into worse clinical outcomes on retrospective analysis of a cohort of BC patients that were closely followed. Indications for SNB did widen and ALND was often skipped in our “liberal” SNB patients, and although they probably presented with slightly more advanced or higher-risk disease, locoregional control, in terms of axillary recurrence, lymph-node recurrence, lymph-node metastases, was the same as for patients in the strict SNB group, who had undergone a tighter indication scheme and fully comprehensive management of the axilla after a positive SN. Neither did the survival rate show a worsening trend in the liberal patient group compared with the strict patient group. There were significant differences in distant metastatic spread between groups (p < 0.001). Indeed, our study groups were remarkably divergent, and many clinical and pathological characteristics pointed to a higher-risk disease profile in the liberal group, which could bring about an increased rate of distant spread. On the other hand, the lack of significant differences in survival could be the result of limited sample size or just too short a follow-up interval as well. It is unclear whether the occurrence of late metastatic spread, especially of visceral metastases, plays a role in the longer term, considering that we are dealing with low-risk patients, as defined by their referral for SNB.

In the light of our retrospective analysis, adoption of the “liberal SNB approach” seems fully justified, because a very important goal for the surgical management in early BC patients is attaining an optimal locoregional disease control, regardless of the unavoidable differences in distant metastatic spread rates across different risk profiles in node-negative patients. Our investigation is limited by its own retrospective nature, and any extrapolation to the wider early BC population must be cautious. More studies are therefore needed to confirm our results. Other non-randomized studies suggest that indication for SLNB could be further extended to patients for whom the standard treatment usually includes complete axillary dissection, such as in locally advanced and widespread multicentric tumors [25]. There are, however, still more controversial indications for SLNB being suggested, such as in node-positive patients who respond to neoadjuvant chemotherapy [26]. Meanwhile, on pure practical grounds, adoption of the liberal use of SNB, as defined in our study, seems an acceptable choice.

SLNB has now well-established “extended” indications in early BC and remains the choice procedure with minimal morbidity, high accuracy, and clinical prognostic significance. Recent advances in multimodality therapy and axillary imaging further highlight the potential for de-escalating axillary surgery and SLNB surely has a pivotal role in such a context.

We wish to thank Mr. Manel Martori for helping us with the graphs, to the members of the Breast Unit, and finally to the staff of the Breast Cancer Screening Unit: Cristina, Sandra, and Clara; all of them were essential contributors in keeping our breast cancer database updated.

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Hospital Universitari Mutua de Terrassa Review Board (Date January 20, 2022, N P/22-012). All patients gave their written consent shortly before breast surgery so that their anonymized individual data, including those from clinical follow-up, could be used for scientific purposes.

The authors have no conflicts of interest to declare.

The authors have no relevant financial or nonfinancial interests to disclose.

Israel Barco, Marc Garcia-Font, Antonio García-Fdez, and Carolina Chabrera contributed to the study conception and design. Elena Vallejo, MCarmen Vidal, Sonia González, Clarisa González, Claudia Beatriz Mitru, Oriol Porta, and Antonio García-Fdez contributed to the material preparation and data collection. Manel Fraile and Antonio García-Fdez contributed to data analysis. The first draft of the manuscript was written by (Israel Barco, Antonio García-Fdez, and Manel Fraile). Manel Fraile was responsible for editing the manuscript. All authors read and approved the final manuscript.

Data from our study patients are not available in the public domain; however, they can be accessed under request to Doctor Antonio García-Fdez, who is responsible for the database of the Breast Unit at the Hospital Universitari Mútua de Terrassa (drgarciafdez@hotmail.com).

1.
Veronesi
U
,
Paganelli
G
,
Galimberti
V
,
Viale
G
,
Zurrida
S
,
Bedoni
M
.
Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes
.
Lancet
.
1997 Jun 28
349
9069
1864
7
.
2.
Fraile
M
,
Rull
M
,
Julian
FJ
,
Fusté
F
,
Barnadas
A
,
Llatjós
M
et al
.
Sentinel node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients: an approach to its validity
.
Ann Oncol
.
2000 Jun
11
6
701
5
.
3.
Lyman
GH
,
Giuliano
AE
,
Somerfield
MR
,
Benson
AB
3rd
,
Bodurka
DC
,
Burstein
HJ
et al
.
American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer
.
J Clin Oncol
.
2005
;
23
(
30
):
7703
20
.
4.
Giuliano
AE
,
Hunt
K
,
Ballman
K
,
Beitsch
PD
,
Whitworth
PW
,
Blumencranz
PW
et al
.
Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial
.
JAMA
.
2011
;
305
(
6
):
569
75
.
5.
Donker
M
,
Straver
ME
,
van Tienhoven
G
,
van de Velde
CJH
,
Mansel
RE
,
Litière
S
et al
.
Comparison of the sentinel node procedure between patients with multifocal and unifocal breast cancer in the EORTC 10981-22023 AMAROS Trial: identification rate and nodal outcome
.
Eur J Cancer
.
2013 jun
49
9
2093
100
.
6.
Piñero-Madrona
A
,
Escudero-Barea
MJ
,
Fernández-Robayna
F
,
Alberro-Adúriz
JA
,
García-Fernández
A
,
Vicente-García
F
et al
.
Selective sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: results of the GEICAM 2005-07 study
.
Cir Esp
.
2015 Jan
93
1
23
9
.
7.
Giuliano
AE
,
Ballman
KV
,
McCall
L
,
Beitsch
PD
,
Brennan
MB
,
Kelemen
PR
et al
.
Effect of axillary dissection vs No axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial
.
JAMA
.
2017 Sep 12
318
10
918
26
.
8.
Galimberti
V
,
Chifu
C
,
Rodriguez Perez
S
,
Veronesi
P
,
Intra
M
,
Botteri
E
et al
.
Positive axillary sentinel lymph node: is axillary dissection always necessary
.
Breast
.
2011 Oct
20
Suppl 3
S96
8
.
9.
Zhu
L
,
Jin
L
,
Li
S
,
Chen
K
,
Jia
W
,
Shan
Q
et al
.
Lymph node metastasis in breast cancer patients? A meta-analysis
.
Breast Cancer Res Treat
.
2013 Feb
137
3
783
95
.
10.
Van la Parra
RF
,
Ernst
MF
,
Bevilacqua
JL
,
Mol
SJJ
,
Van Zee
KJ
,
Broekman
JM
et al
.
Validation of a nomogram to predict the risk of nonsentinel lymph node metastases in breast cancer patients with a positive sentinel node biopsy: validation of the MSKCC breast nomogram
.
Ann Surg Oncol
.
2009
;
16
(
5
):
1128
35
.
11.
Coutant
C
,
Olivier
C
,
Lambaudie
E
,
Fondrinier
E
,
Marchal
F
,
Guillemin
F
et al
.
Comparison of models to predict nonsentinel lymph node status in breast càncer patients with metastàtic sentinel lymph nodes: a prospective multicenter study
.
J Clin Oncol
.
2009
;
27
(
17
):
2800
8
.
12.
Barco
I
,
García-Fernández
A
,
Chabrera
C
,
Fraile
M
,
Vallejo
E
,
Lain
JM
et al
.
The appropriate axillary procedure after a positive sentinel node in breast cancer patients: the “Hôpital Tenon” score revisited. A two-institution study
.
Clin Transl Oncol
.
2016 Nov
18
11
1098
105
.
13.
Swedish Organised Service Screening Evaluation Group
.
Effect of mammographic service screening on stage at presentation of breast càncers in Sweden
.
Cancer
.
2007
;
109
(
11
):
2205
12
.
14.
Barco
I
,
Chabrera
C
,
García Font
M
,
Gimenez
N
,
Fraile
M
,
Lain
JM
et al
.
Comparison of screened and nonscreened breast cancer patients in relation to age: a 2-institution study
.
Clin Breast Cancer
.
2015 Dec
15
6
482
9
.
15.
Rutgers
EJ
.
Sentinel node biopsy: interpretation and management of patients with immunohistochemistry-positive sentinel nodes and those with micrometastases
.
J Clin Oncol
.
2008
;
26
(
5
):
698
702
.
16.
Sola
M
,
Alberro
JA
,
Fraile
M
,
Santesteban
P
,
Ramos
M
,
Fabregas
R
et al
.
Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastasis: final results from the multicenter clinical trial AATRM 048/13/2000
.
Ann Surg Oncol
.
2013
;
20
(
1
):
120
7
.
17.
Meretoja
TJ
,
Leidenius
MH
,
Heikkilä
PS
,
Joensuu
H
.
Sentinel node biopsy in breast cancer patients with large or multifocal tumors
.
Ann Surg Oncol
.
2009 May
16
5
1148
55
.
18.
Knauer
M
,
Konstantiniuk
P
,
Haid
A
,
Wenzl
E
,
Riegler-Keil
M
,
Pöstlberger
S
et al
.
Multicentric breast cancer: a new indication for sentinel node biopsy-a multi-institutional validation study
.
J Clin Oncol
.
2006 Jul 20
24
21
3374
80
.
19.
Chung
MH
,
Ye
W
,
Giuliano
AE
.
Role for sentinel lymph node dissection in the management of large (> or = 5 cm) invasive breast cancer
.
Ann Surg Oncol
.
2001 Oct
8
9
688
92
.
20.
Wong
SL
,
Chao
C
,
Edwards
MJ
,
Tuttle
TM
,
Noyes
RD
,
Carlson
DJ
et al
.
Accuracy of sentinel lymph node biopsy for patients with T2 and T3 breast cancers
.
Am Surg
.
2001 Jun
67
6
522
8
.
21.
Ms
K
,
Rusby
JE
,
Agusti
AA
.
Sentinel Lymph node biopsy after previus axillary surgery: a review
.
Eur J Surg Oncol
.
2012 Jan
38
1
8
15
.
22.
Maaskant-Braat
AJG
,
Voogd
AC
,
Roumen
RMH
,
Nieuwenhuijzen
GAP
.
Repeat sentinel node biopsy in patients with locally recurrent breast cancer: a systematic review and meta-analysis of the literature
.
Breast Cancer Res Treat
.
2013 Feb
138
1
13
20
.
23.
Vugts
G
,
Maaskant-Braat
AJG
,
Voogd
AC
,
van Riet
YEA
,
Luiten
EJT
,
Rutgers
EJT
et al
.
Repeat sentinel node biopsy should be considered in patients with locally recurrent breast cancer
.
Breast Cancer Res Treat
.
2015 Oct
153
3
549
56
.
24.
Lyman
GH
,
Somerfield
MR
,
Bosserman
LD
,
Perkins
CL
,
Weaver
DL
,
Giuliano
AE
.
Sentinel lymph node biopsy for patients with early-stage breast cancer: American society of clinical oncology clinical practice guideline update
.
J Clin Oncol
.
2017 Feb 10
35
5
561
564
.
25.
Mansel
RE
,
Fallowfield
L
,
Kissin
M
,
Goyal
A
,
Newcombe
RG
,
Dixon
JM
et al
.
Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC trial
.
J Natl Cancer Inst
.
2006 May 3
98
9
599
609
.
26.
Charalampoudis
P
,
Markopoulos
C
,
Kovacs
T
.
Controversies and recommendations regarding sentinel lymph node biopsy in primary breast cancer: a comprehensive review of current data
.
Eur J Surg Oncol
.
2018
;
44
(
1
):
5
14
.