Pathology Research International (39.1% versus 33.2% versus 6.1%, resp., P < .0001) and were less likely to receive endocrine therapy alone (9.8% versus 19.4% versus 41.9%, resp., P < .0001). On multivariate analysis, a statistically signiﬁcant diﬀerence in DFS and in the risk of distant metastases was observed for patients with pN1a versus pN0 disease (HR = 2.04; 95% CI, 1.46 to 2.86; P < .0001 for DFS; HR = 2.32; 95% CI, 1.42 to 3.80; P = .0007 for distant metastases) and for patients with pN1mi/pN0i+ versus pN0 disease (HR = 1.58; 95% CI, 1.01 to 2.47; P = .047 for DFS; HR = 1.94; 95% CI, 1.04 to 3.64; P = .037 for distant metastases). In summary, Table 2 shows that pN1mi patients consis- tently have an HR for events of 1.5 versus node-negative patients. Hence despite smaller studies with shorter followup showing no signiﬁcant diﬀerence in outcome [18, 30], with the best available evidence at the present time, the authors of this paper felt that pN1mi patients tend to have worse outcome than node-negative patients. In our institute, medical oncologists tend to treat patients with micrometastases (0.2–2 mm node) with adjuvant sys- temic treatment, while the treatment for nodal metastases <0.2 mm is still debatable. For patients with nodal metastasis ≤2 mm including ITC, the use of nodal radiotherapy is controversial. A muticenters trial for these patients with enough followup duration, and to stratify tumor size, grade and nodal ratio may provide further insight to the role of nodal radiotherapy. 3.2. Completion Axillary Dissection after a Positive SN Biopsy. Another area of recent research on SN biopsy focuses on whether axillary lymph node dissection (ALND) is always necessary when the SN is positive [31]—what is the probability of further nodal metastases in the axilla? Here we examine the available research studies on this issue. A study of 159 stage T1 or T2 breast cancer patients speculated that axillary dissection can be avoided in those patients diagnosed of micrometastasis in the SN [32]. Comple- tion ALND was performed when micro or macrometastases were found in the SN. A total of 40 patients (25%) showed inﬁltration of the SN. This inﬁltration was only by micrometastasis in 17 of them (10.7%). Of these 17 patients, only 2 (11.8%) showed macrometastasis in the lymphadenectomy specimens. 3.2.1. Which Patients Can Be Safely Selected to Forgo Completion ALND? Table 2 shows that if micrometastasis is found in a SN, omission of additional ALND may be envisaged by Houve- naeghel et al. with minimal risk for pT1a and pT1b tumors, and pT1a-b-c tumors corresponding to tubular, colloidal, or medullary cancers [33]. A study from Sa˜o Paulo of 1,000 successive patients with SN biopsy from 1998 to 2008 put this issue into context [34]. The mean age was 57.6 years and mean tumor size was 1.85 cm. A total of 72.2% SN were negative and 27.8% were positive, but in 61.9% of the cases, the SN was the only positive one, with 78.4% having macrometastases, 3 17.3% micrometastases and 4.3% ITCs. After 54 months of followup, there were no recurrences in patients with ITCs, but one local recurrence and two systemic recurrences were observed in the micrometastases group, as well as four local and 30 distant metastases in the macrometastases group. Among the clinical parameters studied, only tumor size was correlated with metastatic involvement in axillary lymph nodes. The size of the metastases and the number of positive SN also directly increased the possibility of systemic recurrence. Volume of disease in the SN is a signiﬁcant predictor of additional nodal metastasis. In a Memorial Sloan-Kettering Cancer Center study of 505 patients, 251 pN0(i+) and 254 pN1mi: 12% of pN0(i+) and 20% pN1mi had additional nonSN disease [35]. On multivariate analyses including eight variables, only lymphovascular invasion (odds ratio > 2.2, P < .01) and volume of nodal metastasis as assessed by any method of measurement (method of detection, AJCC, and cell count) were signiﬁcantly correlated with additional nonSN disease (P = .04, .03, and .02, resp.). More pathologic risk factors were investigated in another study of 128 patients who had a positive SN biopsy in 2005– 2007 [36]. The metastases in each SN were assessed according to their location within the node (subcapsular, mixed subcapsular and parenchymal, parenchymal, multifocal or extensive) and metastatic inﬁltration of perinodal tissue was also reported. The strong predictors of the axillary lymph node metastasis included the SN metastasis diameter (7.6 versus 4.4 mm) and size classiﬁed according to WHO classiﬁcation (ITC 0 versus 100%, micrometastasis 23.5 versus 76.5%, macrometastasis 51.9 versus 48.1%). The SN metastases with a diameter of above 3 mm were associated with approximately twice more frequent ALN metastases. If there is extensive SN metastasis, the highest percentage of ALN metastases was found (65 versus 35%). The weak predictors of ALN metastases were: primary tumor diameter (>2 cm), immunohistochemical HER2 positive status, inﬁl- tration of sentinel perinodal tissue by metastasis, histological primary tumour grade. Two other important concepts to select patients for completion ALND to mention are nomograms and nodal ratio. Nomograms or other scoring systems have been used to predict the chance of involvement of nonSNs after a single involved SN is found [37, 38]. The nodal ratio concept has been extended to SN biopsy. More than one positive SN and a ratio of positive SN(s) to total SN(s) of greater than 0.5 were found to be predictors for additional axillary nodal involvement in both univariate and multivariate analyses [39]. The number of positive SNs and the SN nodal ratio is an indication of total tumor burden in the SNs and may be a reﬂection of the propensity of the tumor for further lymphatic invasion in the axillary basin. 3.2.2. What Is the Signiﬁcance of IHC Positivity in SN Which Is H&E Negative? The surgeons at the St Vincent’s University Hospital in Dublin, Ireland performed SN mapping for breast cancer