Also of note, the frequency of mutations in, for example, TP53, ESR1, and ERBB2 increases with increasing severity of disease, for example CLCIS vs. FLCIS/PLCIS (as noted above), CILC vs. PILC, or primary vs. metastatic ILC (Table 1, and see below), attesting to the importance of these gene alterations in driving a more aggressive tumour biology which, importantly, are linked to endocrine therapy resistance. The gene discussed is ESR1; the disease is neoplasm.