2 Controversies of sentinel node assessment abound. This paper aims to summarize and analyze the current manage- ment of breast cancer following SN biopsy. Recommenda- tions to target readers (clinical oncologists and pathologists) are suggested. 2. Material and Methods A search of PubMed and the proceedings of the American Society for Therapeutic Radiology and Oncology (ASTRO) and American Society of Clinical Oncology (ASCO) annual meeting books was performed and selected relevant articles and abstracts pertinent to SN assessment and prognostic relevance. 3. Results and Discussion The limited number of SNs compared with an axillary dissection has allowed more comprehensive lymph node analysis resulting in increased detection of micrometastases. Many women previously classiﬁed as node-negative are now reclassiﬁed as having micrometastatic nodal involvement. As a result, our nodal classiﬁcation and cancer staging have evolved to recognize the continuum of nodal tumor burden rather than a simplistic dichotomous stratiﬁcation [15]. The pathologist is expected to mount, stain, and microscopically examine serial sections of the SN using hematoxylin and eosin (H&E) staining. Despite recommendations from the College of American Pathologists and the American Society of Clinical Oncology, heterogeneity in the approach to SN evaluation exists. What is needed is adherence to a standard- ized evaluation protocol. The most important aspect of the SN examination is careful attention to slicing the SN with thickness no more than 2.0 mm and correct embedding of the slices to assure all macrometastases larger than 2.0 mm are identiﬁed. 3.1. Is Minimal Lymph Node Involvement Clinically Relevant? There is an ongoing debate concerning the clinical impli- cations of micrometastases in the SN. Many observational studies have been published but results do not justify conclu- sions. Bulte et al. [18] of Netherlands looked at the subgroup of patients with micrometastases (n = 38) : 3 (7.9%) patients developed distant recurrence. In the group with a tumour- free sentinel node (n = 503), 17 (3.4%) distant recurrence and 3 (0.6%) combined regional and distant recurrence were observed. The rates of distant recurrence between the node-negative and micrometastatic cases are not signiﬁcantly diﬀerent (Chi-square test, P = .128). However, the authors reported that the result may be limited by small sample size. Despite the lack of statistical signiﬁcance of outcome of pN1mi in reference 18, to an individual patient the worse outcome is still clinically important. Indeed other studies show that the prognosis of patients with pN1mi is signiﬁcantly worse compared to node- negative patients, in terms of regional and distant recurrence rates [19]. The worse prognosis was further conﬁrmed by Pathology Research International Table 1: Deﬁnition of minimal pathologic lymph node involve- ment in American Joint Committee on Cancer (AJCC) Staging Manual, seventh edition (2010) [16, 17]. pN0(i−) pN0(i+) pN1 pN1mi No regional lymph node metastases histologically, negative immunohistochemistry (IHC) Malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC including isolated tumor cell clusters (ITC)) No regional lymph node metastases histologically, pN0(mol−) negative molecular ﬁndings (RT-PCR, reverse transcriptase/polymerase chain reaction) Positive molecular ﬁndings (RT-PCR), but no pN0(mol+) regional lymph node metastases detected by histology or IHC Micrometastases; or metastases in 1–3 axillary lymph nodes; and/or in internal mammary nodes with metastases detected by sentinel lymph node biopsy but not clinically detected Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm) a large SEER database study [20]: breast cancer speciﬁc survival (BCSS) and overall survival with pNmi disease progressively declined with increasing number of positive nodes and increasing NR. In the MIRROR (Micrometastases and ITCs: Relevant and Robust or Rubbish?) study, almost all participating pathology laboratories used a protocol in which the SN was serially sectioned at least every 150 µm and at a minimum of three levels, with the use of keratin immunohistochemical (IHC) staining if the H&E staining was negative. In contrast, the nonSNs were macroscopically sectioned every 2 to 5 mm, and one section per slice was stained with H&E. The aim was to evaluate the relationship, if any, between ITCs or micrometastases in the regional lymph nodes and clinical outcome in patients who had undergone an SN procedure and who did or did not receive systemic adjuvant therapy. They found that adjuvant treatment helped to lower the risk of disease events [21]. The median followup was 5.1 years. This agrees with large studies that included women who received a diagnosis before the SN era; micrometastases, deﬁned as 2 mm or smaller in diameter and including ITCs, were associated with reduced overall survival [22–25]. In these studies, however, the axillary nodes were examined by means of H&E staining at just one level. Thus, we cannot compare these studies with the MIRROR study, which involved a detailed examination of the SN. The few previous studies of SNs were limited by small samples, lack of multivariate analyses, or short followup [26–28]. It is noteworthy that for patients with minimal nodal involvement, the disease-free survival (DFS) was initially similar but started to fall after the third year compared to node- negative results [29]. Patients with pN1a and pN1mi/pN0i+, when compared with patients with pN0 disease, were more often prescribed anthracycline-containing chemotherapy