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Distinct prognostic patterns of single hormone receptor-positive subtypes in HER2-negative breast cancer: a SEER-based retrospective cohort study

Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Estrogen receptor (ER) and progesterone receptor (PR) expression patterns define clinical subtypes of human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC). However, the characteristics and prognostic implications of single hormone receptor (HR)-positive subtypes remain incompletely characterized, complicating treatment decisions and prognosis assessment. The present study aimed to evaluate the clinicopathological features and survival outcomes predicted by a nomogram in patients with HER2-negative BC. MATERIALS AND METHODS: In this retrospective cohort study, data from 175 585 patients with HER2-negative BC recorded in the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019) were analyzed. A prognostic nomogram was developed and internally validated. RESULTS: The cohort comprised patients with ER+/PR+ (76.5%), ER+/PR- (10.5%), ER-/PR+ (0.7%), and ER-/PR- (12.1%) BC subtypes. Notable variations in clinical features were observed across different HR expression subtypes. ER-/PR+ subtype displayed demographic attributes and characteristics similar to those of ER-/PR-. Univariate analysis demonstrated that BC-specific survival (BCSS) in ER-/PR+ BC was comparable to that in ER-/PR- BC (hazard ratio (HR): 1.072, 95% confidence interval (CI): 0.948-1.213) and worse than that in ER+/PR- BC (HR: 1.466, 95% CI: 1.293-1.662). Multivariable Cox regression analysis revealed significantly worse BCSS for ER+/PR- (HR: 1.69, 95% CI: 1.62-1.76), ER-/PR+ (HR: 2.44, 95% CI: 2.16-2.76), and ER-/PR- subtypes (HR: 2.42, 95% CI: 2.32-2.52) compared to that for ER+/PR+ (all P -value <0.0001). A nomogram model incorporating age, sex, race, grade, histology, stage, and molecular subtype demonstrated good discrimination (optimism-corrected C-index: 0.832) and clinical utility across relevant decision thresholds. CONCLUSIONS: HER2-negative BC subtypes exhibit distinct survival patterns, with single HR-positive cases showing different prognosis. The present study findings may challenge conventional binary ER/PR classification and highlight ER-/PR+ as an independent high-risk factor warranting specialized therapy. The developed nomogram accurately predicted survival, underscoring the importance of clinical decision-making to optimize outcomes in HER2-negative BC patients.
Authors: Jinping Yang, Ying Li, Shunsheng Wang, Yu Fan
Language: English
Subfield: Cancer Research
Open Access status: hybrid
Estimated APC paid: $3,450
OpenAlex ID: W4417434855
FWCI:
Cites: 39
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