Notably, both tamoxifen and chemotherapy, when administered in the adjuvant setting, were associated with a significantly lower risk of undergoing disease recurrence as ERα− BC, thus indicating that in some contexts, ERα−/PgR− clones might originate from HR+ BC clones that undergo modifications in their epigenetic programs, rather than from the selection of initially ERα−/PgR− tumor clones. This evidence concerns the gene ESR1 and breast cancer.