Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
PLoS One. 2022 May 23;17(5):e0268799. doi: 10.1371/journal.pone.0268799. eCollection 2022.
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.
雌激素受体阳性（ER+）乳腺癌对内分泌治疗具有良好的临床疗效。然而，相当一部分 ER+乳腺癌患者对此治疗反应不佳。因此，需要寻找新的标志物来评估内分泌治疗的效果，这些标志物可用于诊断时预测临床结局，尤其是早期和晚期复发。溶质载体家族 20 成员 1（SLC20A1）是一种钠/无机磷酸盐转运体，被认为是 ER+乳腺癌中 luminal A 型和 luminal B 型的一种可行的预后标志物。在本研究中，我们研究了 SLC20A1 表达与 luminal A 和 luminal B 型乳腺癌的肿瘤分期、内分泌治疗和化疗之间的可能相关性。此外，我们分析了 luminal A 和 luminal B 型乳腺癌患者内分泌治疗后 SLC20A1 表达与晚期复发之间的关系。结果表明，SLC20A1 高表达（SLC20A1high）的患者在肿瘤分期为 I 期 luminal A 乳腺癌中临床结局较差。此外，该 SLC20A1high 亚组患者对内分泌治疗的反应较差，尤其是 luminal A 和 luminal B 型乳腺癌患者。然而，SLC20A1high 患者在接受化疗后临床结局良好。在诊断时被检测为 SLC20A1high 组的患者，与 SLC20A1 低表达水平的患者相比，luminal A 乳腺癌的复发率更高，复发时间>15 年，luminal B 乳腺癌的复发时间为 10-15 年。因此，我们得出结论，SLC20A1high 可作为预测 ER+乳腺癌内分泌治疗疗效和晚期复发的预后生物标志物。
