Given that the majority of the PALB2-associated breast cancers were ER+/HER2−, we restricted the comparison of mutation burden to the 12 ER+/HER2− PALB2-associated breast cancers sequenced by WES (median of somatic mutations 125, range 63–269) and the 441 ER+/HER2− non-BRCA1/2/PALB2-associated breast cancers (median somatic mutations 42, range 2–6666), and the difference remained significant (P < 0.0001, Mann–Whitney U test; P = 0.0002, bootstrapping-corrected). Here, ESR1 is linked to breast cancer.