Following successes in difficult-to-treat diseases such as malignant melanoma and lung cancer, checkpoint-targeted immunotherapy has been attempted in a range of solid cancers, including pancreatic ductal adenocarcinoma (PDAC) [1], refractory estrogen receptor (ER)-positive [2] and human epidermal growth factor receptor 2 (HER2)-positive breast cancers [2, 3]. Here, ESR1 is linked to pancreatic ductal adenocarcinoma.