PIK3CA mutations contribute to fulvestrant resistance in ER-positive breast cancer

p110α is an important subunit of phosphatidylinositol-3-kinases (PI3Ks) encoded by PIK3CA. Though PI3Ks are known as crucial regulators of cellular growth and proliferation, the function of PIK3CA mutations in fulvestrant resistance remains elusive. Thus, this study aimed to investigate the roles of PIK3CA mutations in fulvestrant resistance and tumor progression. Using circulating tumor DNA (ctDNA) from four fulvestrant-resistant patients, we found three of them were PIK3CA mutated, one with a novel PIK3CA mutation (p.R115P). In vitro experiments further evaluated the functions of those mutations and underlying mechanisms. We identified PIK3CA mutations could not only confer to fulvestrant resistance, but also promote cell proliferation and migration. Inhibition of corresponding activated pathways could effectively suppress cell growth.