Development and validation of a nomogram for prediction of lymph node metastasis in early-stage breast cancer

Abstract

Background: Lymph node status is an important factor in determining the prognosis of early-stage breast cancer. We endeavored to build and validate a simple nomogram to predict lymph node metastasis (LNM) in patients with early-stage breast cancer.

Methods: Patients with T1-2 and non-metastasis (M0) breast cancer registered in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled. All patients were divided into primary cohort and validation cohort in a 2:1 ratio. In order to assess risk factors for LNM, we performed univariate and multivariate binary logistic regression, and based on results of multivariable analysis, we built the predictive nomogram model. The C-index, receiver operating characteristic (ROC) and calibration plots were applied to assess LNM model performance. Moreover, the nomogram efficiency was further validated through the validation cohort, part of which was from the First Affiliated Hospital of Nanjing Medical University database.

Results: Totally, 184,531 female breast cancer with T1-2 tumor size from SEER database and 1,222 patients from the Chinese institutional data were included. There were 123,019 patients in the primary cohort and 62,734 patients in validation cohort. The LNM nomogram was composed of seven features including age at diagnosis, race, primary site, histologic type, grade, tumor size and subtype. The model showed good discrimination, with a C-index of 0.720 [95% confidence interval (CI): 0.717-0.723] and good calibration. Similar C-index was 0.718 (95% CI: 0.713-0.723) in validation cohort. Consistently, ROC curves presented good discrimination in the primary cohort [area under the curve (AUC) =0.720] and the validation set (AUC =0.718) for the LNM nomogram. Calibration curve of the nomogram demonstrated good agreement.

Conclusions: With the prediction of novel validated nomogram for women with early-stage breast cancer, doctors may distinguish patients with high possibility of LNM and devise individualize treatments.

Keywords: Breast cancer; Surveillance, Epidemiology, and End Results (SEER); early-stage; lymph node metastasis (LNM); nomogram.

Figure 1

Flow chart of the study selection. SEER, Surveillance, Epidemiology, and End Results; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2.

Figure 2

Nomogram predicting the probability of positive lymph nodes. IDC, infiltrating duct carcinoma; ILC, infiltrating lobular carcinoma; ER, estrogen receptor; PR, progesterone receptor; HR, hormonal receptor; HER, human epidermal growth factor receptor; TNBC, triple-negative breast cancer.

Figure 3

Calibration plot of the nomogram for the probability of positive lymph nodes in primary cohort (A) and validation cohort (B). (bootstrap 1,000 repetitions).

Figure 4

Receiver operating characteristic (ROC) curves representing the discriminatory ability of the nomogram in primary cohort (A) and validation cohort (B). AUC, area under the curve; CI, confidence interval.