Development and validation of an extended Cox prognostic model for patients with ER/PR+ and HER2- breast cancer: a...

The purpose of this study was to explore a new estrogen receptor (ER) and/or progesterone receptor (PR)+ and human epidermal growth factor receptor 2 (HER2)- breast cancer prognostic model, called the extended Cox prognostic model, for determining the cutoff values for multiple continuous prognostic factors and their interaction via the new model concept and variable selection method.

A total of 335 patients with ER/PR+ and HER2- breast cancer were enrolled for the final analysis. The primary endpoint was breast cancer-specific mortality (BCSM). Prognostic factors (histological grade, histological type, stage, T, N, lymphovascular invasion (LVI), P53, Ki67, ER, PR, and age) were included in this study. The four continuous variables (Ki67, ER, PR, and age) were partitioned into a series of binary variables that were fitted in the multivariate Cox analysis. A smoothly clipped absolute deviation (SCAD) variable selection method was used. Model performance was expressed in discrimination and calibration.

We developed an extended Cox model with a time threshold of 164-week (more than 3 years) postoperation and developed a user-friendly nomogram based on our extended Cox model to facilitate clinical application. We found that the cutoff values for PR, Ki67, and age were 20%, 60%, and 41-55 years, respectively. There was an interaction between age and PR for patients aged ≥ 41 years and PR ≥ 20% at 164-week postoperation: the older the patients with ER/PR+, HER2-, and PR ≥ 20% were, the lower the survival and more likely to recur and metastasize exceeding 164 weeks (more than 3 years) after surgery.

Our study offers guidance on the prognosis of patients with ER/PR+ and HER2- breast cancer in China. The new concept can inform modeling and the determination of cutoff values of prognostic factors in the future.