Development and validation of an extended Cox prognostic model for patients with ER/PR+ and HER2− breast cancer: a retrospective cohort study

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Nomograms for Predicting Disease-Free Survival Based on Core Needle Biopsy and Surgical Specimens in Female Breast Cancer Patients with Non-Pathological Complete Response to Neoadjuvant Chemotherapy

“…Fujii et al [ 41 ] found that a pre-NAC ER threshold of 10% is a better cut-off for distinguishing ER-positive from ER-negative breast cancer than 1%, but this threshold is based on speculation only and has not been statistically analyzed. In our study, PR was not an independent predictor of patient DFS, which is inconsistent with previous studies [ 30 , 42 ]. We speculate that this situation may be due to the interaction between ER and PR and the different study populations included.…”

“…Here, we discovered that the clinical N stage, ER, Ki67, and p53 were linked to patient DFS results (either pre- or post-NAC ER, Ki67, and p53), which is consistent with previous reports showing that ER expression is a favorable prognostic factor, and lymph node positivity and increased Ki67 and p53 markers have been linked to a worse prognosis [ 15 , 30 , 31 , 32 , 33 , 34 ], but previous studies lacked exploration in the context of NAC for breast cancer conditions. In this condition, the impact of changes in biomarkers such as ER levels during chemotherapy also needs to be considered.…”

“…A recently published study found that Ki67, ER, PR, and age were independent predictors of breast-cancer-specific mortality, but p53 was not [ 30 ]. The reason for the inconsistency with our study may be that the study population was limited to ER/PR+ and HER2- breast cancer patients not receiving NAC, and p53 was simply classified as negative and positive.…”