Metastatic HR+ Breast Cancer

Authored by Open Medicine, published on 2026-04-16 07:47:38.0

Biomarker-driven treatment pathway for advanced HR-positive/HER2-negative metastatic breast cancer, prioritizing endocrine therapy with CDK4/6 inhibition and adapting based on timing of relapse and molecular alterations. Subsequent therapy selection is guided by actionable mutations (e.g., ESR1, PIK3CA, AKT/PTEN, BRCA), enabling targeted treatments such as SERDs, PI3K/AKT inhibitors, and PARP inhibitors.

  1. Advanced / Metastatic HR-positive/HER2-negative Breast Cancer confirmed
    • ET (recurrence ≤12 mos of adj ET)
      • PIK3CA Mut+ Inavolisib + Palbo + Fulvestrant
        • ESR1 mutation
          • Elacestrant / Imlunestrant
            • T-DXd (HER2 IHC ultra-low/low)
            • Chemo
              • Dato-DXd (post chemo)
            • At least 2 prior lines of systemic rx
              • Sacituzumab govitecan
        • PIK3CA mutation
          • Alpelisib + Fulvestrant
            • Chemo
              • Dato-DXd (post chemo)
            • T-DXd (HER2 IHC ultra-low/low)
            • At least 2 prior lines of systemic rx
              • Sacituzumab govitecan
        • PIK3CA / AKT1 / PTEN alteration
          • Capivasertib + Fulvestrant
            • T-DXd (HER2 IHC ultra-low/low)
            • Chemo
              • Dato-DXd (post chemo)
            • At least 2 prior lines of systemic rx
              • Sacituzumab govitecan
        • gBRCA mutation
          • PARPi
            • Chemo
              • Dato-DXd (post chemo)
            • T-DXd (HER2 IHC ultra-low/low)
            • At least 2 prior lines of systemic rx
              • Sacituzumab govitecan
        • Everolimus + Exemestane OR Fulvestrant-based Therapy +/- CDK4/6 Inhibitor
          • T-DXd (HER2 IHC ultra-low/low)
          • Chemo
            • Dato-DXd (post chemo)
          • At least 2 prior lines of systemic rx
            • Sacituzumab govitecan
    • Endocrine Therapy + Abemaciclib OR Ribociclib
      • ESR1 mutation
        • Elacestrant / Imlunestrant
          • T-DXd (HER2 IHC ultra-low/low)
          • Chemo
            • Dato-DXd (post chemo)
          • At least 2 prior lines of systemic rx
            • Sacituzumab govitecan
      • PIK3CA mutation
        • Alpelisib + Fulvestrant
          • Chemo
            • Dato-DXd (post chemo)
          • T-DXd (HER2 IHC ultra-low/low)
          • At least 2 prior lines of systemic rx
            • Sacituzumab govitecan
      • PIK3CA / AKT1 / PTEN alteration
        • Capivasertib + Fulvestrant
          • T-DXd (HER2 IHC ultra-low/low)
          • Chemo
            • Dato-DXd (post chemo)
          • At least 2 prior lines of systemic rx
            • Sacituzumab govitecan
      • gBRCA mutation
        • PARPi
          • Chemo
            • Dato-DXd (post chemo)
          • T-DXd (HER2 IHC ultra-low/low)
          • At least 2 prior lines of systemic rx
            • Sacituzumab govitecan
      • Everolimus + Exemestane OR Fulvestrant-based Therapy +/- CDK4/6 Inhibitor
        • T-DXd (HER2 IHC ultra-low/low)
        • Chemo
          • Dato-DXd (post chemo)
        • At least 2 prior lines of systemic rx
          • Sacituzumab govitecan
tosprivacyYouTube: Metastatic Hormone Receptor Positive (HR+) Breast Cancer Treatment Algorithm: Dr. Kevin KalinskyNCCN Breast Cancer 1L guidelinesA Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120)FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancerINAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC).Overall Survival with Ribociclib plus Letrozole in Advanced Breast CancerAbemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR-positive, HER2-negative advanced breast cancer: final overall survival results of MONARCH 3FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancerElacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD TrialAlpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer (SOLAR-1)FDA approves alpelisib for metastatic breast cancerFDA approves capivasertib with fulvestrant for breast cancerCapivasertib and fulvestrant for patients with hormone receptor-positive advanced breast cancer: characterization, time course, and management of frequent adverse events from the phase III CAPItello-291 studyCapivasertib in Hormone Receptor-Positive Advanced Breast Cancer (CAPItello-291)FDA approves olaparib for germline BRCA-mutated metastatic breast cancerFDA approves talazoparib for gBRCAm HER2-negative locally advanced or metastatic breast cancerOlaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation (OlympiAD)Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation (EMBRACA)FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancerEMERALD: Pivotal trial in ESR1-mutated, ER+/HER2- mBC patients with 100% prior ET + CDK4/6i exposure and prior chemotherapy permittedEverolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast CancerEverolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole (BOLERO-2)Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial.A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial.FDA approves fam-trastuzumab deruxtecan-nxki for HER2-low breast cancerPatient-reported outcomes with trastuzumab deruxtecan in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer: results from the randomized DESTINY-Breast06 trialFDA approves sacituzumab govitecan-hziy for HR-positive breast cancerOverall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trialFDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer