Anterior Gradient 2 is a Poor Outcome Indicator in Luminal Breast Cancer

Recent data have shown anterior gradient 2 (AGR2) to be a novel oncogene overexpressed in luminal breast cancers. However, many studies only focused on its relationship with treatment resistance, and the clinical relevance of AGR2 has not been widely evaluated.

AGR2 expression in a cohort of breast cancer was correlated with the clinicopathologic features, biomarker expression, and patient survival.

AGR2 expression correlated with lower grade (p = 0.002) and absence of necrosis (p = 0.001) and was most highly expressed in luminal cancers (p < 0.001). Correspondingly, AGR2 correlated positively with estrogen receptor, progesterone receptor, and androgen receptor (p < 0.001) and negatively with epidermal growth factor receptor (p = 0.002) and CK5/6 (p < 0.001). AGR2 was an independent unfavorable disease-free survival prognostic factor in patients with hormone therapy (hazard ratio 2.537, p = 0.023). Interestingly, it was also an independent adverse disease-free survival prognostic factor in node-positive luminal cancers (hazard ratio 3.381, p = 0.016). AGR2 expression was higher in nodal metastasis than the corresponding primary tumors in luminal cancers (p = 0.023).

The prognostic impact of AGR2 expression could be related to treatment outcome in estrogen receptor–positive breast cancers and/or its metastasis-promoting effects. It could be an important tumor biomarker and negative prognostic factor potentially exploitable in clinical practice.