Breast cancer continues to be the most frequently diagnosed malignancy among women worldwide and represents a leading cause of cancer-related mortality. The assessment of axillary lymph node status remains one of the most critical prognostic factors in the management of breast carcinoma, providing essential information for treatment planning, estimation of disease recurrence risk, and determination of overall survival outcomes. Historically, axillary lymph node dissection (ALND) was considered the gold standard for axillary staging, offering comprehensive information about nodal involvement. However, this extensive procedure was associated with considerable morbidity including lymphedema, shoulder dysfunction, chronic pain, sensory disturbances, and decreased quality of life. The quest for less invasive yet equally accurate staging methods led to the development of sentinel lymph node biopsy (SLNB), which has fundamentally transformed axillary management in breast cancer over the past three decades. The landmark study by Veronesi and colleagues demonstrated that SLNB provided comparable staging accuracy to conventional axillary dissection while significantly reducing surgical morbidity, establishing this technique as the standard of care for clinically node-negative breast cancer patients.² The subsequent NSABP B-32 trial, enrolling over five thousand patients, confirmed that SLNB was equivalent to ALND in terms of regional control and survival outcomes while carrying substantially lower morbidity.⁴ These pivotal trials fundamentally altered clinical practice and established SLNB as the preferred method for axillary staging in early-stage, clinically node-negative breast cancer.

The management paradigm becomes considerably more complex, however, when metastatic disease is identified within the sentinel lymph node. The presence of SLN metastasis traditionally mandated completion ALND, based on the assumption that additional non-sentinel nodes harboured metastatic deposits requiring removal for optimal locoregional control. Nevertheless, accumulating evidence demonstrated that approximately 40–60% of patients with a positive SLN had no evidence of metastatic disease in the remaining axillary nodes on completion dissection.¹ This observation raised fundamental questions about the therapeutic necessity of ALND in all SLN-positive patients and stimulated intensive research to identify clinicopathological factors that could reliably predict the likelihood of non-sentinel node involvement. Among the various parameters investigated, the characteristics of the metastatic deposit within the sentinel node itself emerged as particularly significant determinants. Reynolds and colleagues demonstrated through multivariate analysis that macrometastasis — defined as deposits greater than 2.0 mm — was significantly associated with higher likelihood of non-sentinel node involvement, whereas patients with micrometastases measuring 2.0 mm or less, particularly those with small primary tumours, had minimal risk of additional nodal disease.¹ This finding was corroborated by subsequent investigations and led to the AJCC classification system that categorises nodal metastases based on size into macrometastases, micrometastases, and isolated tumour cells. Turner and colleagues further demonstrated that the size of the metastatic deposit within the sentinel node, along with extranodal extension and lymphovascular invasion, were independent predictors of non-sentinel node metastasis.⁶ The American College of Surgeons Oncology Group Z0011 trial represented another watershed moment, demonstrating that among patients with clinical T1–T2 invasive breast cancer, clinically negative axillary nodes, and one or two positive SLNs treated with breast-conserving surgery and whole-breast radiation, there was no significant difference in overall survival between those who underwent completion ALND and those who did not.³ This trial fundamentally challenged the assumption that ALND was therapeutically essential for all sentinel node-positive patients.

Advances in pathological evaluation have further enhanced our understanding of SLN metastases. Weaver and colleagues emphasised the importance of standardised protocols for SLN examination — including serial sectioning and immunohistochemical analysis — which significantly increased detection of micrometastases compared to conventional single-section examination.⁷ Stitzenberg and colleagues demonstrated that extranodal extension in the SLN was a significant predictor of non-sentinel node tumour burden and identified a subset of patients who may benefit from more aggressive locoregional therapy.⁸ Goyal and colleagues identified several independent predictors of non-sentinel node metastasis including tumour size, lymphovascular invasion, and the method of sentinel node detection.⁹ The ratio of positive sentinel lymph nodes to total nodes examined has also emerged as a significant predictor of non-sentinel node involvement.¹⁰ The development of reliable predictive factors has profound clinical implications — enabling selective application of completion ALND to patients most likely to benefit while sparing low-risk patients from unnecessary surgery and its morbidity. The present prospective study aims to comprehensively evaluate the correlation between sentinel lymph node size and metastatic status and the presence of metastatic disease in non-sentinel axillary lymph nodes among breast carcinoma patients at KMCRI, Hubballi, contributing regional evidence to inform evidence-based, individualised axillary management.

This prospective cohort study was conducted at the Department of General Surgery, Karnataka Medical College and Research Institute, Hubballi, over 18 months from September 2024 to March 2026. The sample size was calculated using the formula n = (Z₁₋α/₂)² × P × (1-P) / d², yielding a calculated sample of 84; after excluding 14 patients in whom the SLN was not detected, the final sample size was 70. Inclusion criteria comprised female patients with early-stage carcinoma breast undergoing modified radical mastectomy. Patients with prior radiotherapy or neoadjuvant chemotherapy, prior axillary clearance, or advanced-stage disease (N2, N3, Stage IV) were excluded. All enrolled patients underwent comprehensive preoperative evaluation including clinical examination, haematological and biochemical investigations, mammography, ultrasonography, and FNAC for diagnostic confirmation. Patients with clinically negative axillae were selected for SLNB. Methylene blue dye (10 mg/ml) was injected both intralesionally (1 ml) and perilesionally (2–5 ml) approximately 20 minutes prior to surgery under anaesthesia. Modified radical mastectomy (Auchincloss technique) was performed, through which complete axillary clearance up to level III and sentinel node identification were accomplished. Blue-stained lymph nodes were identified as sentinel nodes; their maximum diameter was measured intraoperatively using vernier calipers and recorded in millimetres. After excision of sentinel nodes, all remaining axillary lymph nodes were separately harvested. All specimens were subjected to histopathological examination using haematoxylin and eosin staining. Metastatic deposits were classified as macrometastasis (>2 mm), micrometastasis (0.2–2 mm), or isolated tumour cells (<0.2 mm). Tumour characteristics including size, histological type, grade, and receptor status (ER, PR, HER2) were recorded. Data were entered into Microsoft Excel and analysed using descriptive statistics. Categorical variables were expressed as frequencies and percentages; continuous variables as mean ± SD. Fisher's Exact Test was used to assess associations between categorical variables, and the independent samples t-test was used for continuous variable comparisons. A p-value of less than 0.05 was considered statistically significant. Ethical clearance was obtained from the Institutional Ethics Committee of KMCRI prior to study initiation, and written informed consent was obtained from all participants.

Seventy female patients with carcinoma breast undergoing MRM with SLNB and completion ALND were prospectively studied. SLN identification was achieved using the methylene blue dye technique; SLN size was measured intraoperatively with vernier calipers; and metastatic status was classified histopathologically as macrometastasis (>2 mm), micrometastasis (0.2–2 mm), or isolated tumour cells (<0.2 mm). ALN involvement was assessed from the completion axillary dissection specimen.

Table 1: Patient Demographics, Tumour Characteristics, and Receptor Status (n = 70)

Table 1 summarises the baseline demographic, tumour, and receptor characteristics of the 70 patients. The majority were in the 51–60 years age group (38.6%), with a mean age of 51.53 ± 8.797 years, consistent with the peak incidence of breast cancer in the perimenopausal and postmenopausal decades. All patients were female. More than half presented with T2 disease (54.3%) and a mean tumour size of 2.11 ± 0.506 cm, reflecting an early-stage cohort. IDC was the dominant histological type (81.4%), consistent with established epidemiology. ER and PR positivity rates of 74.3% and 65.7%, respectively, reflect the hormone receptor-driven nature of the disease in this cohort. HER2 positivity was observed in 14.3%, in keeping with published prevalence rates.

Table 2: SLN and ALN Characteristics (n = 70)

Table 2 presents the SLN and ALN characteristics. SLN positivity was found in 17.1% of patients (n = 12), with macrometastasis the more prevalent type among SLN-positive patients (10.0%, n = 7), while micrometastasis was identified in 7.1% (n = 5). A mean of 2.77 ± 1.038 SLNs were retrieved per patient, with a mean SLN size of 7.36 ± 1.527 mm. ALN positivity was documented in 8.6% of patients (n = 6), with the mean total ALN retrieved of 11.63 ± 2.335 confirming adequacy of axillary dissection. Among ALN-positive cases, micrometastasis was more common (5.7%) than macrometastasis (2.9%).

Table 3: SLN Metastatic Type vs. ALN Status and ALN Metastasis Type (Fisher's Exact Test)

Table 3 demonstrates the critical relationship between SLN metastatic type and ALN status. Among patients with SLN macrometastasis (n = 7), 4 patients (66.7% of ALN-positive cases) had ALN positivity. In stark contrast, none of the patients with SLN micrometastasis (n = 5) had any ALN involvement — a difference that was highly statistically significant (p < 0.001). Extending the analysis to the type of ALN metastasis, SLN macrometastasis was the only subgroup associated with both ALN micrometastasis and ALN macrometastasis (2.9% each), while SLN micrometastasis was associated with no ALN metastatic disease of any type (p < 0.001). These findings confirm that the nature of SLN metastatic burden directly and significantly determines the risk and type of non-sentinel axillary nodal disease.

Table 4: Mean SLN Size and Tumour Size by ALN Status (Independent Samples t-Test) and T Stage vs. ALN Status (Fisher's Exact Test)

*Statistically significant (p < 0.05)

Table 4 presents the quantitative relationship between SLN size, primary tumour size, T stage, and ALN status. The mean SLN size was significantly larger in ALN-positive patients (9.35 ± 1.140 mm) compared to ALN-negative patients (7.18 ± 1.428 mm; p = 0.001), establishing SLN size as a robust intraoperative predictor of further axillary nodal involvement. By contrast, primary tumour size did not significantly differ between ALN-positive and ALN-negative groups (1.90 ± 0.607 cm vs. 2.13 ± 0.496 cm; p = 0.284). Similarly, T stage was not a significant predictor of ALN positivity (p = 0.402). Additional analyses showed that age category (p = 0.113), histopathological type (p = 0.114), ER status (p = 0.490), PR status (p = 0.526), and number of SLNs retrieved (p = 0.474) were all non-significant predictors of SLN or ALN status.

Breast cancer remains the most prevalent malignancy among women globally and a leading cause of cancer-related mortality. The axillary lymph node status is among the most important determinants of staging, prognosis, and treatment planning. The advent of SLNB in the 1990s fundamentally transformed axillary management, offering a minimally invasive and accurate method to stage the nodal basin while sparing patients the morbidity of routine complete axillary dissection.¹¹'¹² Despite the widespread adoption of SLNB, the optimal management of patients found to have a positive sentinel node remains debated — specifically, which subset of SLN-positive patients harbour additional non-sentinel axillary metastases and therefore require completion ALND. The present study was undertaken to evaluate axillary lymph node metastasis in relation to the size and metastatic status of the sentinel lymph node in carcinoma breast patients undergoing MRM at KIMS Hubballi. The mean age of the study population was 51.53 ± 8.797 years, with the 51–60 years group comprising the largest proportion (38.6%), consistent with the well-established peak incidence of breast cancer in perimenopausal and early postmenopausal decades. Pandey VK et al (2020)¹³ reported that SLN-positive patients were younger on average (mean 36 years) than SLN-negative patients (mean 52 years), suggesting more aggressive disease biology in younger patients. In the present study, the highest proportion of SLN positivity was noted in the 30–40 years age group, although the overall association between age and SLN status was not statistically significant (p = 0.113). IDC was the dominant histological type (81.4%), consistent with published data.¹⁴ Neither histological type (p = 0.114) nor receptor status (ER p = 0.490, PR p = 0.526) showed a significant association with SLN positivity, concordant with findings by Chauhan MN et al (2020)¹⁵ and Mittendorf E et al (2012),¹⁶ who similarly found receptor status to be a non-significant predictor of non-sentinel node involvement. The SLN positivity rate in the present study was 17.1%, comparable to the 16.7% reported by Pandey VK et al (2020).¹³ T2 disease was the predominant stage (54.3%), and the mean tumour size was 2.11 ± 0.506 cm. Neither T stage (p = 0.402) nor primary tumour size (p = 0.284) was a significant predictor of ALN positivity. While Baker TA et al (2012)¹⁷ and Mittendorf E et al (2012)¹⁶ found tumour size to be a significant predictor of non-SLN involvement on univariate analysis in pT1-focused cohorts, the absence of this association in the present study likely reflects the relatively small number of ALN-positive patients (n = 6) and the predominance of early-stage disease. The most critical finding pertains to the relationship between SLN tumoral load and ALN involvement [Table 3]. Among patients with SLN macrometastasis (n = 7), 66.7% (n = 4) had ALN positivity, while none of the patients with SLN micrometastasis (n = 5) had any ALN involvement — a difference that was highly statistically significant (p < 0.001). This is strongly concordant with the existing literature. Baker TA et al (2012)¹⁷ reported non-SLN positivity in 18% of micrometastasis versus 39% of macrometastasis patients (p = 0.04). Chauhan MN et al (2020)¹⁵ identified macrometastasis in the SLN as the only significant predictor of non-sentinel node involvement. Mittendorf E et al (2012)¹⁶ incorporated SLN metastasis size as the most important variable in their predictive nomogram (AUC = 0.80; p < 0.001). Pandey VK et al (2020)¹³ reported 35% non-sentinel ALN positivity in the macrometastasis group versus 4.86% in the micrometastasis group. With respect to SLN size [Table 4], a highly significant difference was found between ALN-positive patients (mean SLN size 9.35 ± 1.140 mm) and ALN-negative patients (7.18 ± 1.428 mm; p = 0.001), establishing SLN size as a reliable intraoperative predictor of additional axillary disease. This finding closely mirrors the results of Pandey VK et al (2020),¹³ who reported mean SLN diameters of 10.8 mm and 7.4 mm in SLN-positive and SLN-negative patients respectively (p < 0.03), and proposed a threshold of 7.5 mm as predictive of metastatic involvement. The mean SLN size of 9.35 mm in ALN-positive patients in the present study exceeds this threshold, further validating its clinical utility. Mittendorf E et al (2012)¹⁶ and Baker TA et al (2012)¹⁷ also incorporated SLN metastasis size as an independent variable in predictive models, with positive likelihood ratios for non-SLN disease increasing with larger metastatic deposits (LR 1.1 for micrometastasis vs. 1.6 for macrometastasis). Nandu VV et al (2017)¹⁸ reported SLNB sensitivity of 90.48% and accuracy of 88.57% in predicting axillary status, reinforcing the reliability of the sentinel node as a representative of the axillary basin. The finding that ALN positivity was exclusively associated with SLN macrometastasis and entirely absent in patients with SLN micrometastasis strongly supports contemporary trends toward omitting completion ALND in patients with solely micrometastatic sentinel node involvement,¹⁹'²⁰ and endorses a selective, risk-stratified approach to axillary management.

This prospective study demonstrates that sentinel lymph node metastatic type and SLN size are statistically significant and clinically reliable predictors of additional axillary lymph node involvement in patients with early-stage carcinoma breast. SLN macrometastasis was associated with a substantially higher rate of ALN positivity (66.7%), whereas SLN micrometastasis carried no demonstrable additional axillary risk in our cohort. A significantly larger mean SLN size in ALN-positive patients (9.35 ± 1.140 mm) compared to ALN-negative patients (7.18 ± 1.428 mm; p = 0.001) further establishes intraoperative SLN size measurement as a pragmatic and reproducible bedside tool. Primary tumour size, T stage, histological type, and receptor status were not significant predictors of ALN involvement. Taken together, these findings support a risk-stratified approach to axillary management: patients with SLN micrometastasis may safely be spared completion ALND, thereby reducing surgical morbidity without compromising oncological outcomes, while patients with SLN macrometastasis or larger SLN size warrant careful consideration for completion axillary lymph node dissection. These parameters should be incorporated into individualised decision-making frameworks to optimise the balance between locoregional disease control and quality of life in early breast cancer.

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