A recent study showed that NF1 mutations contribute to the genomic evolution towards metastasis and are prevalent in recurrent, ER + breast cancers.55 Considering our demonstration that (1) NF1 shallow deletions correlate with poor outcome, (2) network connectivity exists between NF1-ER-FOXA1-AR, and (3) broad response of Nf1 tumors to ovariectomy, it is likely that NF1 is a key factor in endocrine resistance. The gene discussed is ESR1; the disease is breast cancer.