An early amendment resulted in the testing of all patients with ER+ breast cancer who had node-negative or 1–3N+ disease.26,31 Those with ER+, pN0 or pN1 disease, and RS <12 received endocrine therapy only (after a protocol amendment) and those with RS ≥12 were randomized to one of two chemotherapy regimens. Here, ESR1 is linked to breast cancer.