Treatment implications on breast cancer patients and alterations in ARID1A

Abstract

ARID1A (AT-rich interaction domain 1A), is a subunit of the SWI/SNF complexes specifically mutated in ~20% of primary human cancers. Inactivation of ARID1A through somatic mutations and other epigenetic mechanisms results in loss of gatekeeper and caretaker functions in cells, promoting tumor initiation. A correlation has been documented between loss-of-function mutations in ARID1A and the presence of activating mutations in PIK3CA, loss of PTEN expression and loss of p53 function.

ARID1A mutations were present in 2.5% of all breast cancers. However, the percentage of breast cancer with ARID1A mutations increases in metastatic 12% or inflammatory 10% cancers. Loss of ARID1A function in breast cancer is most frequently acquired post-treatment and is associated with resistance to hormonal treatment and chemotherapeutic agents. In addition, it leads to deficient repair of double-strand breaks, sensitizing cells to PARP inhibitors. Finally, alterations in ARID1A could be a biomarker of response to checkpoint inhibitors.