High expression of SLC20A1 is less effective for endocrine therapy and predicts late recurrence in ER-positive breast cancer

PLoS One. 2022 May 23;17(5):e0268799. doi: 10.1371/journal.pone.0268799. eCollection 2022.

Abstract

Estrogen receptor-positive (ER+) breast cancer intrinsically confers satisfactory clinical outcomes in response to endocrine therapy. However, a significant proportion of patients with ER+ breast cancer do not respond well to this treatment. Therefore, to evaluate the effects of endocrine therapy, there is a need for identification of novel markers that can be used at the time of diagnosis for predicting clinical outcomes, especially for early-stage and late recurrence. Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter that has been proposed to be a viable prognostic marker for the luminal A and luminal B types of ER+ breast cancer. In the present study, we examined the possible association of SLC20A1 expression with tumor staging, endocrine therapy and chemotherapy in the luminal A and luminal B subtypes of breast cancer. In addition, we analyzed the relationship between SLC20A1 expression and late recurrence in patients with luminal A and luminal B breast cancer following endocrine therapy. We showed that patients with higher levels of SLC20A1 expression (SLC20A1high) exhibited poorer clinical outcomes in those with tumor stage I luminal A breast cancer. In addition, this SLC20A1high subgroup of patients exhibited less responses to endocrine therapy, specifically in those with the luminal A and luminal B subtypes of breast cancer. However, patients with SLC20A1high showed good clinical outcomes following chemotherapy. Patients tested to be in the SLC20A1high group at the time of diagnosis also showed a higher incidence of recurrence compared with those with lower expression levels of SLC20A1, at >15 years for luminal A breast cancer and at 10-15 years for luminal B breast cancer. Therefore, we conclude that SLC20A1high can be used as a prognostic biomarker for predicting the efficacy of endocrine therapy and late recurrence for ER+ breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Neoplasm Recurrence, Local / metabolism
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Sodium-Phosphate Cotransporter Proteins, Type III / metabolism

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SLC20A1 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type III
  • Receptor, ErbB-2

Grants and funding

The research was supported by Grant-in-Aid for Scientific Research (C) of JSPS, Tokyo, Japan (20K07207) (K.A.), Tokyo University of Science Grant for President's Research Promotion (K.A.), JST Moonshot R&D, Saitama, Japan (JPMJPS2022) (S.O.), Grant-in-Aid for JSPS Research Fellows, Tokyo, Japan (21J13718) (H.M.) and (20J11980) (S.T.), Grant-in-Aid for Research Activity Start-up, Tokyo, Japan (21K20732) (S.T.), and Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan, Tokyo, Japan (A.O. and H.M.).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.