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Although prognostic markers for early estrogen receptor ( ER )‐positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of  ER ‐positive breast cancer cells was correlated with the expression of aspartate‐β‐hydroxylase ( ASPH ), which is involved in the development of hepatocellular carcinoma.  ASPH  expression in  ER ‐positive and tamoxifen‐resistant breast cancer cells was upregulated by the  MAPK  and phosphoinositide‐3 kinase ( PI 3K) pathways, which both play pivotal roles in endocrine resistance. In the clinical setting,  ASPH  expression was negatively correlated with recurrence‐free survival of luminal B breast cancer patients that received adjuvant endocrine therapy, but not in patients that did not receive adjuvant endocrine therapy. Luminal B breast cancer is one of the intrinsic molecular subtypes identified by the Prediction Analysis of Microarray 50 ( PAM 50) multiple gene classifier, and because of its poor response to endocrine therapy, chemotherapy in addition to endocrine therapy is generally required after surgical resection. Our results suggest that the endocrine sensitivity of luminal B breast cancer can be assessed by examining  ASPH  expression, which promotes the consideration of a prospective study on the association between  ASPH  expression at the  mRNA  and protein levels in luminal B breast cancer and subsequent response to endocrine therapy.

Endocrine sensitivity of estrogen receptor‐positive breast cancer is negatively correlated with aspartate‐β‐hydroxylase expression