Population
Among 2423 patients with SLNB for BC mastectomy we reported 1307 pN0(i-)SN, 120 pN0(i+)SN, 273 pN1miSN and 723 pN1macroSN. cALND has been performed for 1306 patients (53.9%), in 24.5, 73.3, 82.4 and 93.1% for SN pN0(i-), pN0(i+), pN1mi and pN1macro, respectively. Factors associated with pN final status with or without cALND are reported in Table 1.
Median follow-up was 42.72 months (mean: 51.33, CI95%: 49.9-52.8, range: 0.26-211). We reported 120 death and 213 recurrences including 152 metastases and 21 axillary recurrences and 40 local breast recurrence or unknown as first event.
pN0(i-) SN status
Among 1307 patients with pN0(i-)SN, 320 underwent an additional ALND, mainly before publication of NSABP B-32 trial results1. We observed 35 LN macro metastases at cALND (10.9%) and false negative rate (FNR) was 3.63% among 964 patients with LN involvement (35/964) at cALND with pathologic results known or at SN.
In binary logistic regression, cALND was significantly associated with grade, LVI, ER, tumor size and periods of treatment. Adjuvant chemotherapy (AC), post-mastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) were delivered more frequently for patients with cALND, including 95.4% (21/22) of AC and 97.1% (34/35) of PMRT for patients with involved NSN at cALND. (Table 2).
In Cox regression analysis, OS and DFS were not significantly different according to cALND or not (Table 3, 4). AR rates were 1.4% for patients without cALND (14/987) and 0.3% with cALND (1/320) (p: 0.086): 2.8% (9/323) and 0.8% (5/660) for patients without cALND respectively with and without PMRT, 0.4% (1/225) and 0% (0/95) for patients with cALND respectively with and without PMRT (p: 0.039: cALND or not for patients with PMRT).
pN1 macro metastases SN status
Among 723 patients with SN macro-metastases, cALND was omitted in only 50 patients (6.9%). Among patients with involved-SN number known, only one SN macro-metastases was observed in 372 patients and more than one in 257 patients: 124 patients with only one SN macro-metastases had one or more NSN-involved at cALND (124/332: 37.3%). AC and PMRT were delivered more frequently for patients with cALND (Table 2). In Cox regression analysis, OS and DFS were not significantly different according to cALND or not (Table 3, 4). AR rates were 1.0 and 0% respectively for patients with and without cALND (7/673 vs 0/50), 0.9% and 2.5% respectively for patients with and without PMRT (6/683 vs 1/40: p=0.330).
pN0(i+) and pN1mi SN status
Among 120 patients with pN0(i+) SN and 273 patients with pN1mi SN, cALND were respectively omitted in 32 patients (26.7%) and 48 patients (17.6%) (Table 2).
One or several macro-metastases in NSN at cALND was observed in 6 patients with pN0(i+) SN (6/88: 6.8%, 1 NSN positive for 4 patients, 2 and 6 NSN positive for 2 others) and 30 patients with pN1mi (30/225: 13.3%, 1 NSN positive for 21 patients, 2 NSN positive for 7 patients, 3 and 6 NSN positive for 2 others).
In univariate analysis, age, pT size and SN status were significantly predictive of NSN involvement among patients with pN0(i+) or pN1mi SN and cALND (Table 5). These factors remained significant in binary logistic regression (Table 5).
Four groups were determined according to pT tumor size < or >= 20mm and age > or <= 40 years-old with NSN involvement rate for pN0(i+) and pN1mi from 0 to 65%. In binary logistic regression cALND was not significantly associated to these 4 sub-groups and SN status (Table 6).
For pN0(i+) and for pN1mi, AC and PMRT was delivered more frequently for patients with cALND, including for patients with involved NSN at cALND 100% (5/5) and 92.3% (24/26) of AC, 83.3% (5/6) and 100% (30/30) of PMRT for pN0(i+) and pN1mi respectively (Table 2).
For pN0(i+) and pN1mi according to cALND or not, PMRT rate was significantly different only for patients with pT<20mm/age>40 years-old, RNI rate was significantly different for patients with pT<20mm/age>40 years-old and pT<20mm/age<=40 years-old, AC rate was significantly different for patients with pT<20mm/age>40 years-old and pT>=20mm/age>40 years-old (Supplementary Table 1).
In binary logistic regression, PMRT, RNI and AC were significantly associated with cALND but also to SN status and pT/age sub-groups (Table 6).
In univariate analysis (Log Rank), OS and DFS was lesser and significantly different for patients with pN0(i+) SN without cALND (respectively, p: 0.012 and <0.0001), but without difference for pN1mi SN (respectively, p: 0.985 and 0.180). In Cox regression analysis (Tables 3-4), OS were not significantly different according to cALND or not for patients with pN0(i+) or pN1mi (HR: 2.063, CI95%: 0.439-9.693, p: 0.359) and a significant difference was observed for DFS with lesser survival rate for patients without cALND (HR: 3.861, CI95%: 1.660-8.982, p: 0.002) without other significant criteria (ET, AC, LVI, age, SN status, PMRT and RNI) (Fig. 1).
In Cox regression analysis adjusted on endocrine therapy (ET), SN status and pT/age (< or >=20mm/<= or >40 years-old), omission of cALND was negatively associated to DFS (HR: 4.023, CI95%: 1.896-8.534, p<0.001) and no ET had also a borderline negative association (HR: 2.755, CI95%: 0.988-7.684, p: 0.053). Omission of cALND and no ET were negatively associated to RFS (respectively, HR: 3.187, CI95%: 1.379-7.363, p: 0.007 and HR: 3.968, CI95%: 1.399-11.25, p: 0.010). On OS adjusted on ET, SN status, pT/age (< or >=20mm/<= or >40 years-old), LVI, only no ET was negatively associated to OS (HR: 7.985, CI95%: 1.346-47.37, p: 0.022) without significant difference for cALND or not (HR: 2.904, CI95%: 0.733-11.51, p: 0.129).
AR rates were no significantly different according to cALND or not and PMRT or not, 0% (0/31) and 0% (0/49) for patients without cALND, 0.8% (2/246) and 1.5% (1/67) for patients with cALND respectively with and without PMRT.