Identifying gene expression predictive of response to neoadjuvant endocrine therapy in early breast cancer

TL;DR

This study identifies genes that predict how well breast cancer patients respond to endocrine therapy, helping guide personalized treatment.

Contribution

The study discovers CXCL9 and NPY1R as novel predictive biomarkers for response to neoadjuvant endocrine therapy in breast cancer.

Findings

CXCL9 and ABCA12 were upregulated in patients with poor response to endocrine therapy.

NPY1R was significantly upregulated in patients showing a favorable response to treatment.

CXCL9 and NPY1R were confirmed as significant predictors of Ki67 reduction in multivariate analysis.

Abstract

Estrogen receptor (ER)-positive breast cancer is the most common subtype, accounting for approximately 80% of cases, with endocrine therapy as the standard postoperative treatment. However, despite risk-reducing therapies, the risk of recurrence remains substantial. Studies, including the POETIC trial, have demonstrated that low Ki67 levels following short-term neoadjuvant endocrine therapy (sNAET) are associated with a favorable prognosis. The objective of this study is to identify genes associated with the suppression of cell cycle progression by sNAET in postmenopausal patients with ER-positive/human epidermal growth factor receptor 2-negative breast cancer.

Ninety-seven tissue samples were collected and classified into groups based on Ki67 expression levels before and after treatment. RNA sequencing and real-time quantitative reverse transcription PCR were performed to analyze gene expression in tumor samples from patients stratified into High–High (H–H) or High–Low (H–L) groups based on Ki67 levels before and after sNAET.

Among the differentially expressed genes identified, CXCL9 and ABCA12 were significantly upregulated in the H–H group and were associated with a poor response to endocrine therapy. Conversely, NPY1R was significantly upregulated in the H–L group, suggesting greater responsiveness. In multivariate logistic regression analysis, CXCL9 (OR: 0.65, p = 0.024) and NPY1R (OR: 1.61, p = 0.048) were significant predictors of Ki67 reduction.

These findings suggest that CXCL9 and NPY1R could serve as predictive biomarkers for endocrine therapy response. Identifying these biomarkers may facilitate personalized treatment strategies, including the addition of therapies such as chemotherapy for resistant cases.

The online version contains supplementary material available at 10.1007/s10549-025-07693-8.

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