Characteristics and survival in bone metastatic breast cancer patients with different hormone receptor status: A population-based cohort study

Abstract

Background: Accumulating preclinical evidence has uncovered the indispensable role of steroid hormone and their receptors, namely, estrogen receptor (ER) and progesterone receptor (PR), in the development of bone metastases in breast cancer. Limited data are available regarding the survival difference between different hormone receptor (HR) subgroups, and its prognostic significance is uncertain now. Such data are important for risk stratification and needed to formulate specialized regimen for bone metastatic breast cancer.

Methods: From the year of diagnosis 2010 to 2018, 554,585 breast cancer patients, among which are 19,439 with bone metastasis and 10,447 with bone-only metastasis, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis was performed to compare the survival difference between the different HR status subgroups. Univariate and multivariate Cox proportional hazard regression was used to validate the prognostic role of HR status and identify other prognostic factors in bone metastatic breast cancer.

Results: ER-positive/PR-positive breast cancer patients with bone metastasis showed the best breast cancer-specific survival (BCSS) and overall survival (OS) than those with other HR statuses, while single PR-positive bone metastatic breast cancers manifest similar survival with ER-negative/PR-negative ones. Adjusted Cox regression analysis demonstrated that patients with older age, male, black race, ILC, higher tumor grade, T3-T4, HER2-negative status, absence of surgery or adjuvant treatment, and HR status other than ER-positive/PR-positive tended to have worse outcomes. Further subgroup analysis based on HER2 status showed that within HER2-positive breast cancers, ER-positive/PR-positive ones still manifest better survival than the other three HR status subgroups, which are similar in survival outcomes.

Conclusion: Although collectively viewed as HR-positive breast cancers, certain distinctions exist between bone metastatic breast cancers with different HR statuses in survival outcome. Our findings indicate that despite metastasizing to the same location, the different survival rate is determined by the HR status of breast cancer. The selection and intensity of the regimen should consider HR status, and HER2 status occasionally, when treating bone metastatic breast cancer.

Keywords: HER2 status; SEER (Surveillance Epidemiology and End Results) database; bone metastasis; breast cancer; hormone receptor (HR).

Figure 1

Flowchart of the cohort selection.

Figure 2

Survival analysis of bone metastatic breast cancer patients stratified by hormone receptor status. (A) Kaplan–Meier survival curves show a breast cancer-specific survival rate difference. (B) Kaplan–Meier survival curves show an overall survival rate difference. (C, D) Data are presented as hazard ratios (95% CIs) between HR status subgroups regarding BCSS and OS. A hazard ratio exceeding 1 favors the column-labeled HR status subgroup.

Figure 3

Subgroup BCSS analysis in HER2-positive and negative bone metastatic breast cancers stratified by HR status. (A) Kaplan–Meier survival curves show the BCSS rate difference in HER2-positive bone metastatic breast cancers stratified by HR status. (B) Kaplan–Meier survival curves show the BCSS rate difference in HER2-negative bone metastatic breast cancers stratified by HR status. (C, D) Data are presented as hazard ratios (95% CIs) between HR status subgroups regarding BCSS in HER2-positive and negative bone metastatic breast cancers. A hazard ratio exceeding 1 favors the column-labeled HR status subgroup.

Figure 4

Subgroup BCSS analysis in (A) ER-positive/PR-positive, (B) ER-positive/PR-negative, (C) ER-negative/PR-positive, and (D) ER-negative/PR-negative bone metastatic breast cancers stratified by HER2 status.