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High p62 and ALDH1A3 Reduce the Effectiveness of Endocrine Therapy in Luminal B Breast Cancer
Yuki Maemura1, Ayaka Ozaki1, Ryosuke Chiwaki1
1Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan.
Background/Aim:
High expression of p62 and ALDH1A3 indicates a poor clinical outcome in luminal B breast cancer, and p62 is involved in the progression of ALDH1-positive luminal B breast cancer stem cells. However, the association between endocrine therapy and high p62 and ALDH1A3 expression, in luminal B breast cancer remains unclear.
Materials And Methods:
Two datasets with gene expression and clinical data for patients with primary breast cancer (METABRIC, n=2,509; The Cancer Genome Atlas, n=1,084) were downloaded and statistically analyzed. To evaluate the association between the p62 and ALDH1A3 expression levels and endocrine therapy, including tamoxifen and aromatase inhibitor, in patients with luminal B breast cancer, disease-specific survival was examined using Kaplan-Meier and multivariate Cox regression analyses.
Results:
Patients with p62 high ALDH1A3 high luminal B breast cancer treated with endocrine therapy exhibited a poor prognosis. Moreover, patients with p62 high ALDH1A3 high luminal B breast cancer treated with tamoxifen showed a trend towards a poor prognosis, but those treated with aromatase inhibitors showed a significantly poor prognosis. These results suggest that endocrine therapy, especially aromatase inhibitors, exhibits a reduced effectiveness against p62 high ALDH1A3 high luminal B tumors.
Conclusion:
p62 and ALDH1A3 could be used together as a prognostic biomarker for predicting the efficacy of endocrine therapy for luminal B breast cancer.
