Nomograms for preoperative prediction of axillary nodal status in breast cancer

Abstract

Background: Axillary staging in patients with breast cancer and clinically node-negative disease is performed by sentinel node biopsy (SLNB). The aim of this study was to integrate feasible preoperative variables into nomograms to guide clinicians in stratifying treatment options into no axillary staging for patients with non-metastatic disease (N0), SLNB for those with one or two metastases, and axillary lymph node dissection (ALND) for patients with three or more metastases.

Methods: Patients presenting to Skåne University Hospital, Lund, with breast cancer were included in a prospectively maintained registry between January 2009 and December 2012. Those with a preoperative diagnosis of nodal metastases were excluded. Patients with data on hormone receptor status, human epidermal growth factor receptor 2 and Ki-67 expression were included to allow grouping into surrogate molecular subtypes. Based on logistic regression analyses, nomograms summarizing the strength of the associations between the predictors and each nodal status endpoint were developed. Predictive performance was assessed using the area under the receiver operating characteristic (ROC) curve. Bootstrap resampling was performed for internal validation.

Results: Of the 692 patients eligible for analysis, 248 were diagnosed with node-positive disease. Molecular subtype, age, mode of detection, tumour size, multifocality and vascular invasion were identified as predictors of any nodal disease. Nomograms that included these predictors demonstrated good predictive abilities, and comparable performances in the internal validation; the area under the ROC curve was 0·74 for N0 versus any lymph node metastasis, 0·70 for one or two involved nodes versus N0, and 0·81 for at least three nodes versus two or fewer metastatic nodes.

Conclusion: The nomograms presented facilitate preoperative decision-making regarding the extent of axillary surgery.

Figure 1

Study flow chart. *Sentinel node biopsy (SLNB) showed solitary micrometastasis; false‐negative frozen section of the involved node. †Presumed multifocality at the time of diagnosis; represents a selected group included in a study protocol with preplanned SLNB + axillary lymph node dissection (ALND). ER, oestrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; N0, lymph node‐negative; N+(1), solitary lymph node metastasis; N+(1–2), lymph node metastasis involving one or two nodes; N+(≥ 3), lymph node metastasis involving at least three nodes

Figure 2

Nomograms predicting the extent of axillary nodal disease: a disease‐free axilla (N0) versus any nodal metastasis (N+); b low‐volume axillary disease involving one or two nodes (N+(1–2)) versus N0; and c high‐volume axillary disease involving at least three nodes (N+(≥ 3)) versus N0 and N+(1–2). The total score for each patient is assigned by drawing a vertical line from the appropriate point for each predictor down to the score scale, and summing these scores. To obtain the predicted probability of a specific nodal status, a vertical line is drawn from the total score scale up to the predicted probability scale in the lower part of the nomogram. *Subtypes: 1, luminal A‐like; 2, luminal B‐like (LumB)/human epidermal growth factor receptor 2 (HER2)‐negative; 3, LumB/HER2‐positive; 4, HER2‐positive/non‐luminal; 5, triple‐negative

Figure 3

Receiver operating characteristic (ROC) curves representing the discriminatory ability of the nomograms in predicting axillary nodal status. N0, lymph node‐negative; N+(1–2), lymph node metastasis involving one or two nodes; N+(≥ 3), lymph node metastasis involving at least three nodes

Figure 4

Scatterplot of number of metastatic axillary nodes versus tumour size stratified by breast cancer molecular subtype. Trend lines (dotted) are shown only to facilitate comparison among the five molecular subtypes. LumA, luminal A‐like; LumB, luminal B‐like; HER2, human epidermal growth factor receptor 2