Clinical Significance of ABCG2/BCRP Quantified by Fluorescent Nanoparticles in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

SIMPLE SUMMARY: Breast cancer resistance protein (BCRP) is a drug efflux pump associated with chemotherapy resistance. Effective quantitative analysis of BCRP expression in breast cancer tissue is essential for predicting breast cancer survival. Our laboratory developed nanoparticles suitable for quantitative immunohistochemical (IHC) analysis, called phosphor-integrated dots (PIDs). We examined the association between BCRP expression and prognosis among primary breast tumor sites and metastatic lymph nodes after neoadjuvant chemotherapy (NAC) in 37 breast cancer patients using IHC with PIDs at the single-particle level. The results show that overall survival was significantly worse in the high-BCRP-expression group (log-rank p = 0.0089). Quantitative BCRP expression analysis of primary tumors and breast cancer metastases could predict the prognosis of breast cancer patients after NAC. The IHC-PIDs were effective at the quantitative detection of the biomarker protein. ABSTRACT: Breast cancer resistance protein (BCRP), also known as ATP-binding cassette transporter G2 (ABCG2), is associated with chemotherapy resistance. BCRP is also implicated in breast cancer stem cells, and is reported as a poor prognostic factor. However, the relationship of BCRP levels in breast cancer tissues with chemotherapy resistance and prognosis has not been clarified. We aimed to evaluate the correlation between BCRP expression and prognosis in breast cancer using immunohistochemistry with fluorescent phosphor-integrated dots (IHC-PIDs). A total of 37 breast cancer patients with residual cancer in the primary tumor and axillary lymph nodes were evaluated. BCRP levels in breast cancer tissue and metastatic lymph nodes were quantitatively detected after neoadjuvant chemotherapy (NAC). Among these 37 patients, 24 had corresponding core needle biopsies obtained before NAC. Biomarker assay with IHC-PIDs showed high accuracy for the quantitative assessment of BCRP with low expression. High BCRP expression in the primary tumor and metastatic lymph nodes after preoperative chemotherapy was associated with worse overall survival. In conclusion, high BCRP levels may be associated with poor prognosis in patients with breast cancer, having residual tumors within the primary tumor and lymph nodes after preoperative chemotherapy. These findings provide a basis for further appropriate adjuvant therapy in these patients.