Some known disease susceptibility alleles confer differential risks of different tumor subtypes that are associated with different outcomes—for example, deleterious alleles of BRCA1 are associated with estrogen receptor (ER)–negative disease, and several common germline genetic variants that are associated with susceptibility to breast cancer have different risks of ER-positive and ER-negative disease (5,6). The gene discussed is ESR1; the disease is breast cancer.