Fig. 2. Current and future treatment paradigms for HR + /HER2− ABC.

Blue boxes indicate current treatment options based on FDA-approved drugs and the latest NCCN¹⁶², ESMO, ASCO guidelines^2,3. Pink boxes indicate the potential therapeutic strategies in the future, which are currently still investigational. Dotted pink arrows indicate the possibility of switching between treatments, or change in sequence of the treatment options, pending further data. ADC antibody–drug conjugate, AR androgen receptor, DDRi DNA damage repair inhibitor, dMMR deficient mismatch repair, ET endocrine therapy, ESR1 estrogen receptor 1 gene, gBRCA mut germline BRCA1/BRCA2 mutation (now termed variant), HRD homologous recombination deficiency, MAPK mitogen-activated protein kinase, MSI-H microsatellite instability high, NTRK neutotrophic tyrosine receptor kinase, PALB2 mut partner and localizer of BRCA2 mutation, RET rearranged during transfection, T-DXd trastuzumab deruxtecan, TMB-H tumor mutational burden high, TP53 transformation-related protein 53.