Construction and Validation of Nomograms Predicting Survival in Triple-Negative Breast Cancer Patients of Childbearing Age

Abstract

Background: Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with poorest clinical outcomes. Patients of childbearing age have a higher probability of TNBC diagnosis, with more demands on maintenance and restoration of physical and psychosocial function. This study aimed to design effective and comprehensive nomograms to predict survival in these patients.

Methods: We used the SEER database to identify patients with TNBC aged between 18 and 45 and randomly classified these patients into a training (n=2,296) and a validation (n=2,297) cohort. Nomograms for estimating overall survival (OS) and breast cancer-specific survival (BCSS) were generated based on multivariate Cox proportional hazards models and competing-risk models in the training cohort. The performances of the nomograms were quantified in the validation cohort using calibration curves, time-dependent receiver operating characteristic (ROC) curves and Harrell's concordance index (C-index).

Results: A total of 4,593 TNBC patients of childbearing age were enrolled. Four prognostic factors for OS and six for BCSS were identified and incorporated to construct nomograms. In the validation cohort, calibration curves showed excellent agreement between nomogram-predicted and actual survival data. The nomograms also achieved relatively high Harrell's C-indexes and areas under the time-dependent ROC curves for estimating OS and BCSS in both training and validation cohorts.

Conclusions: Independent prognostic factors were identified, and used to develop nomograms to predict OS and BCSS in childbearing-age patients with TNBC. These models could enable individualized risk estimation and risk-adapted treatment for these patients.

Keywords: SEER; breast cancer-specific survival; childbearing age; nomogram; overall survival; prediction; prognosis; triple-negative breast cancer.

Figure 1

Nomograms predicting 3- and 5-year (A) overall survival (OS) and (B) breast cancer-specific survival (BCSS) in TNBC patients of childbearing age. Instructions for nomogram use were as follows. First, assign points to each characteristic for a given patient by drawing a vertical line from that variable to the points scale. Then, sum all the points and draw a vertical line from the total points scale to the 3- and 5-year OS or BCSS to obtain the likelihood of 3- or 5-year survival.

Figure 2

Calibration curves for external validation. (A) Nomogram calibration curves for 3- and 5-year overall survival (OS). (B) Nomogram calibration curves for 3- and 5-year breast cancer-specific survival (BCSS). X-axis, nomogram-predicted survival; Y-axis, actual survival.

Figure 3

Time-dependent receiver operating characteristic (ROC) curves for predicting 3- and 5-year OS and BCSS. (A) Internal validation in the training cohort. (B) External validation in the validation cohort. AUC, area under curve; OS, overall survival; BCSS, breast cancer-specific survival.