HR+ Early Breast Cancer

HR+ Early Breast Cancer: overview

This algorithm covers HR-positive early-stage breast cancer and branches on nodal burden, then menopausal status and the recurrence score (RS), to decide between endocrine therapy (ET) alone and chemotherapy followed by ET.

For node-negative disease (TAILORx), all patients undergo surgery. Premenopausal patients with RS 1 to 15 receive ET, those with RS 16 to 25 derive some benefit from chemotherapy then ET, and those with RS 26 or higher receive chemotherapy (TC) then ET. Postmenopausal patients with RS 1 to 25 receive ET, and RS 26 or higher receive TC then ET. For 1 to 3 positive nodes (RxPONDER), premenopausal patients with RS 1 to 25 choose between chemotherapy and ovarian function suppression plus an aromatase inhibitor before ET, and RS 26 or higher receive chemotherapy (TC or ddAC-T) then ET. Postmenopausal patients with RS 1 to 25 receive ET alone, and RS 26 or higher receive chemotherapy then ET. With 4 or more positive nodes, ddAC-T then ET follows surgery. Selected high-risk patients may receive adjuvant escalation: abemaciclib for 2 years (monarchE, node-positive high risk), ribociclib for 3 years (NATALEE, stage II to III), or olaparib for 1 year (OlympiA, germline BRCA, high risk).

Step by step

• Node negative, premenopausal: surgery, then ET for RS 1 to 15, chemotherapy then ET with some benefit for RS 16 to 25, and TC then ET for RS 26 or higher (TAILORx).
• Node negative, postmenopausal: surgery, then ET for RS 1 to 25 and TC then ET for RS 26 or higher (TAILORx).
• 1 to 3 positive nodes, premenopausal: surgery, then chemotherapy versus OFS plus AI before ET for RS 1 to 25, and chemotherapy (TC or ddAC-T) then ET for RS 26 or higher (RxPONDER).
• 1 to 3 positive nodes, postmenopausal: surgery, then ET for RS 1 to 25 and chemotherapy then ET for RS 26 or higher (RxPONDER).
• 4 or more positive nodes: surgery, then ddAC-T chemotherapy, then ET.
• Selected high-risk patients: adjuvant escalation with abemaciclib for 2 years (monarchE), ribociclib for 3 years (NATALEE), or olaparib for 1 year if germline BRCA (OlympiA).

Trials behind this algorithm

• ATAC trial Baum M et al, Lancet, 2002; PMID: 12090977
• TAILORx Sparano JA et al, N Engl J Med, 2018; PMID: 29860917
• CALGB 9741 trial Citron ML et al, JCO,2003; PMID:12668651
• monarchE Johnston SRD et al, JCO, 2020; PMID: 32954927
• NATALEE Hortobagyi GN et al, Ann Oncol, 2024; PMID: 39442617
• OlympiA Tutt AN et al, NEJM, 2021; PMID: 34081848

Background reading: Breast Cancer (Part 2): DCIS, Early-Stage and Metastatic Treatment board review notes.