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Development and validation of a prognostic nomogram for early HER2-positive and lymph node-negative breast cancer.

ABSTRACT:

Background

Dual-targeted therapy is currently the standard adjuvant treatment for human epidermal growth factor receptor 2-positive (HER2+) and lymph node-positive (LN+) breast cancer. However, the optimal therapeutic strategy for patients with HER2+ and lymph node-negative (LN-) breast cancer remains unclear. This population-based study aimed to explore the factors associated with survival in patients with HER2+ and LN- breast cancer, and develop a survival-predicting nomogram in the era of trastuzumab-based single-targeted therapy.

Methods

We collected the clinicopathological information of HER2+ and LN- breast cancer patients who underwent chemotherapy and surgery from The Surveillance, Epidemiology, and End Results (SEER) database (2010-2016, the Trastuzumab-based single-targeted therapy era). We subsequently explored the risk factors for breast cancer-specific survival (BCSS) and overall survival (OS) using a Cox proportional hazards regression model, aiming to identify subgroups with worse prognosis, which would indicate potential demand for dual-targeted therapy. Three- and 5-year survival probability-predictive nomograms were established and subjected to bootstrap internal validation. The concordance index (C-index) and calibration curve were applied to evaluate the performance of the model.

Results

After data cleansing, a total of 13,755 patients were included in the current analysis. Using univariate and multivariate Cox proportional hazards regression, higher clinical T stage, hormone receptors-negative (HR-), and partial mastectomy without radiotherapy were identified as independent risk factors for BCSS and OS in patients with HER2+ and LN- breast cancer. Nomograms for 3- and 5-year BCSS and OS incorporating the selected prognostic factors were established. Calibration curves verified good consistency between the actual and nomogram-predicted survival probability. The C-index values of the BCSS and OS predictions and 95% confidence interval (CI) were 0.773 (0.740-0.806) and 0.764 (0.737-0.791), respectively.

Conclusions

Higher clinical T stage, HR-, and partial mastectomy without radiotherapy predicted worse prognosis in patients with HER2+ and LN- breast cancer. In clinical practice, patients can be recommended for single-targeted or dual-targeted therapy according to the individualized factors.

SUBMITTER: Shi Q

PROVIDER: S-EPMC8340331 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe hormone receptor+/human epidermal growth factor receptor 2- (HR+/HER2-) breast cancer (BC) patients account for the largest proportion in all patients and are still at high risk of long-range recurrence. This current study aimed to construct a prognostic nomogram to predict 3-year and 5-year BC-specific survival (BCSS) in HR+/HER2- BC patients with axillary lymph node metastasis.MethodsA total of 25,338 HR+/HER2- patients with axillary lymph node-positive BC were enrolled from the Surveillance, Epidemiology and End Results (SEER) database and randomly divided into the training (n=17,738) and validation (n=7,600) cohorts using a ratio of 7:3. Univariate and multivariable Cox regression hazards were used to build a prognostic nomogram based on the training cohort. The nomogram was validated with two independent cohorts. Receiver operating characteristic (ROC) curves and calibration plots were used to evaluate the performance of the model, and Kaplan-Meier survival analyses were applied to test the clinical utility of the risk stratification system.ResultsTwelve factors including age, race, marital status, grade, T stage, N stage, radiotherapy, chemotherapy, and metastasis to the bone, brain, lung and liver were identified and incorporated to construct the nomogram (P<0.001). The area under the ROC curve (AUC) values at 3- and 5-year in the training and internal validation sets were 0.800, 0.800, 0.831 and 0.819, respectively, while those of the external set were 0.765 and 0.735, indicating a satisfactory discrimination with our nomogram. The calibration curves showed highly consistent results for the actual and predicted survival probabilities. Furthermore, patients were divided into three risk groups according to the total scores of the nomogram. The risk stratification system accurately differentiated between patients with different BCSS rates.ConclusionsWe constructed the first nomogram and corresponding risk stratification system to predict the 3-year and 5-year BCSS for HR+/HER2- patients with lymph node-positive BC, indicating a satisfactory accuracy and clinical application.