Decreased expression of PDCD4 has been linked with resistance to aromatase inhibitors in preclinical models, while high expression is associated with a good outcome in HR+ disease.33,34 Thirdly, MAP3K1, a serine–threonine kinase, has been shown to mediate apoptosis through activation of the JNK proapoptosis protein.35 Interestingly, somatic inactivating mutations in MAP3K1 are present in 8% of breast cancers, with luminal A tumors having a higher mutation rate than luminal B tumors.10–12. This evidence concerns the gene PDCD4 and breast cancer.