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PIK3CA mutations resulting in disinhibition of the phosphoinositide 3-kinase (PI3K) pathway are present in approximately a third of estrogen receptor (ER)-positive breast cancer. Recent clinical trials of PI3K inhibition in PIK3CA-mutated metastatic breast cancer have shown improvement in progression-free survival of up to 11 months. We report a 68-year-old woman with metastatic ER-positive breast cancer with PIK3CA mutation who despite having disease progression after four lines of endocrine therapy (ET) attained a complete response (CR) after subsequent addition of a PI3K inhibitor. Remarkably, her CR is still maintained at 5 years. We believe this may be due to the co-occurrence of an NF1 mutation, which increases sensitivity to PI3K inhibition. Our case demonstrates restoration of sensitivity to ET by additional inhibition of PI3K, which resulted in exceptional disease response, far exceeding the expected duration. Hence, we believe that PI3K inhibition in addition to ET should be considered in patients with simultaneous PIK3CA and NF1 mutations.

Case Report: Sustained Complete Response to PI3K Inhibition in a Patient with Metastatic Breast Cancer Harboring PIK3CA, NF1, and CDH1 Mutations