HR-positive / HER2-negative breast cancer: guideline history

Anchored to: FDA approvals of ribociclib (March 2017) and abemaciclib (September 2017) after palbociclib (2015)

• addedMetastatic, first line: All three CDK4/6 inhibitors with an aromatase inhibitor listed as category 1 first-line options.

Anchored to: FDA approval of adjuvant abemaciclib, October 2021 (monarchE)

• addedAdjuvant, high risk: Abemaciclib for 2 years with endocrine therapy for node-positive, high-risk HR-positive early breast cancer (initially Ki-67 20% or above, later removed).

Anchored to: Annals of Oncology publication, November 2021

• recategorisedMetastatic, first line: CDK4/6 inhibitor plus endocrine therapy stated as the standard first-line treatment for most patients; chemotherapy reserved for visceral crisis.option → standard of care [I, A]
• addedMetastatic, PIK3CA-mutant after endocrine therapy: Alpelisib plus fulvestrant for PIK3CA-mutated disease after aromatase inhibitor.

Anchored to: FDA approvals of elacestrant (January 2023) and capivasertib (November 2023)

• addedMetastatic, ESR1-mutant after CDK4/6: Elacestrant for ESR1-mutated disease after at least one line of endocrine therapy (EMERALD).
• addedMetastatic, PIK3CA/AKT1/PTEN-altered: Capivasertib plus fulvestrant after progression on an aromatase inhibitor (CAPItello-291).

Anchored to: FDA approvals of adjuvant ribociclib (September 2024, NATALEE) and inavolisib (October 2024, INAVO120)

• addedAdjuvant, stage II-III: Ribociclib for 3 years with an aromatase inhibitor for stage II-III HR-positive early breast cancer, including node-negative high-risk disease.
• addedMetastatic, PIK3CA-mutant, endocrine-resistant: Inavolisib plus palbociclib and fulvestrant for PIK3CA-mutated disease relapsing during or within 12 months of adjuvant endocrine therapy.

Anchored to: FDA approvals of trastuzumab deruxtecan for HER2-low or ultralow disease after endocrine therapy (January 2025, DESTINY-Breast06) and imlunestrant (September 2025, EMBER-3)

• recategorisedMetastatic, HER2-low, chemotherapy-naive: Trastuzumab deruxtecan moved earlier: now an option after one or more endocrine lines and before chemotherapy in HER2-low and HER2-ultralow disease.after chemotherapy (DESTINY-Breast04) → after endocrine therapy, before chemotherapy (DESTINY-Breast06)
• addedMetastatic, ESR1-mutant: Imlunestrant added as an oral SERD option for ESR1-mutated disease after endocrine therapy.