Abstract P6-01-45: Correlation of an immune-related 8-gene panel with the efficacy of neoadjuvant chemotherapy for breast cancer

Abstract

Abstract Introduction: Neoadjuvant chemotherapy, one of systemic treatment of breast cancer, is employed for downstaging of inoperable tumor. Pathological complete response (pCR) after neoadjuvant chemotherapy is associated with good prognosis for breast cancer. The critical role of anti-tumor immune responses in conventional chemotherapy and targeted therapy has been reported. However, the pCR-associated immune genes are still ambiguous. Materials and Methods: Thirty-seven primary breast cancer patients receiving neoadjuvant chemotherapy as the first-line treatment for breast cancer were recruited in this VGH-TAYLOR study (NCT04626440). Total RNA of fresh tumor tissues was isolated and then reverse transcribed into cDNA. The Oncomine Immune Response Research Assay was employed for examination of immune-related gene expressions. In silico analyses were performed using the public databases, including Gene Expression Omnibus, Kaplan-Meier plotter, ROC Plotter, Cancer Therapeutics Response Portal, and The Cancer Genome Atlas. Results: Patients achieved a pCR were associated with lower tumor stage and HER2 expression. The next-generation sequencing-based analysis showed that the expression of eight genes were higher in tissues of patients with pCR than non-pCR, including KLRK1, IGJ, CD69, CD40LG, MS4A1, CD1C, KLRB1, and CA4. The 8-gene score was associated with better recurrence-free survival in patients receiving chemotherapy. Data from an ROC Plotter database showed that higher expressions of IGJ, CD69, and MS4A1 in patients respond to neoadjuvant chemotherapy compared to non-responders. In silico analysis revealed that the negative correlation between pCR-associated gene expressions and IC50 values suggesting the gene high expression was sensitive to the drugs. Moreover, the levels of pCR-associated gene were downregulated in breast tumor tissues and positively correlated with immune cell infiltrations. Conclusion: We identified eight immune genes which were associated with better prognosis and drug responses. The 8-gene score may serve as a prognostic marker for breast cancer patients who receiving neoadjuvant chemotherapy. Citation Format: Chun-Yu Liu, Chi-Cheng Huang, Yi-Fang Tsai, Ta-Chung Chao, Yen-Shu Lin, Chin-Jung Feng, Jiun-I Lai, Ji-Lin Chen, Yen-Jen Chen, Jen-Hwey Chiu, Chih-Yi Hsu, Ling-Ming Tseng. Correlation of an immune-related 8-gene panel with the efficacy of neoadjuvant chemotherapy for breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-45.