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In the past decade, with the introduction of precision medicine, the treatment of breast cancer has entered a new era. It now tends towards the de-escalation and individualization of treatment plans, aiming to minimize iatrogenic toxicity while maximizing benefits for patients without compromising survival outcomes. The 21-gene assay evaluates the expression levels of 21 genes associated with breast cancer recurrence and provides a 21-gene recurrence score (RS) to assess the risk of recurrence and potential benefit from chemotherapy in breast cancer patients. Currently, RS is recommended by multiple guidelines such as the American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), and Chinese Anti-Cancer Association(CACA) for guiding adjuvant therapy in hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer patients. However, there are still controversies surrounding its clinical application. Current research mainly focuses on optimizing RS to accurately identify patients who would benefit from adjuvant therapy, thus enabling more personalized treatment plans for breast cancer patients. This review provides an overview of the 21-gene assay, its application in HR+ breast cancer patients' adjuvant therapy, its impact on clinical decision-making, existing controversies regarding RS, and prospects for integrating RS with clinical pathological information. The aim is to guide further expansion of RS's application in clinical practice and achieve more precise adjuvant therapy for breast cancer patients.

Breast cancer is the most common malignancy in women. Clinical models such as Oncotype DX recurrence score (RS) and Clinical Treatment Score post–5 years (CTS5) model for survival prediction are crucial for clinical practice. However, it remains unclear whether CTS5 or RS would be a more powerful clinical model for recurrence risk evaluation. Therefore, we conducted the present study to compare the performance of CTS5 risk model and RS on different recurrence evaluation. And we further integrated the two models into a novel nomogram to improve the power for prognosis prediction. Female patients with invasive hormone receptor positive breast cancer in the Surveillance, Epidemiology, and End Results Program (SEER) database with RS data available were included. The clinicopathological data were directly extracted from SEER database. Participants were divided into three subsets according to recurrence timing (<36 months, between 36 and 60 months, and >60 months) for model evaluation. Survival receiver operating characteristic curve and C-index were calculated to evaluate discrimination. Calibration curve were used to visual inspection for calibration. Model comparison was assessed by net reclassification index (NRI) method. Nomogram prognostic model was developed with the combination of CTS5 score and RS and also included other critical clinicopathological parameters. In total, 64044 breast cancer patients were enrolled for analysis. The number of patients with survival <36 months (early recurrence subset), 36–60 months (intermediate recurrence subset) and >60 months (late recurrence subset) were 64044, 36878 and 15926, respectively. For model discrimination, CTS5 model was superior to RS for overall survival (OS) prediction (likelihood ratio test P < 0 0.001). RS model showed better performance for breast cancer specific survival (BCSS) in late recurrence subsets and worse performance in early and intermediate recurrence subsets than CTS5 (likelihood ratio test P < 0 0.001). For calibration, CTS5 model was superior to RS model for OS, which overestimated the recurrence risk in low-risk subgroup. Both models overestimated the risk for BCSS. In either early/intermediate/late recurrence patient subsets, there was no significant difference in NRI between two models in terms of both BCSS and OS, indicating the two models had comparable prognostic value. The nomogram which combined these two models largely improved the discrimination and calibration power (C-index 0.70–0.72). Our study proved the CTS5 risk model had comparable prognostic value as RS in HR + breast cancer patients. And the novel nomogram model had better discrimination and calibration than both CTS5 and RS, and future large-scale clinical trials are warranted for further validation. [ABSTRACT FROM AUTHOR]