PTEN hamartoma tumour syndrome (PHTS) is characterized by a germline PTEN mutation and a substantial increase in lifetime breast cancer risk to 85% with lower age at first diagnosis. Despite the availability of agents targeting PTEN-regulated PI3K/AKT/mTOR pathway, there are currently no approved treatments for PHTS patients with cancer. This is the first report of a patient with triple-negative metaplastic breast cancer and PHTS in the literature. We present an exceptional response of this aggressive stage IV tumour in a 34-year-old woman with PHTS to treatment with the novel AKT1-3 inhibitor, TAS-117. Despite previous rapid progression and resistance to multi-agent chemotherapy and radiotherapy, disease stabilisation was ongoing at 3.8 years. Cell-free DNA analysis of blood samples at baseline and during treatment with TAS-117 revealed a complete marker response to treatment. Therapy has been well tolerated, and the patient continues the therapy without severe adverse events, dose reduction, or treatment interruptions. These findings support further investigation of targeted interventions for malignancies developing in the context of PHTS.
Godina et al. (Wed,) studied this question.