HR+/HER2- Advanced Breast Cancer

Authored by Ilana Schlam, published on 2026-04-13 18:09:39.0

  1. HR+/HER2- advanced disease
    • PD on adjuv ET or within 12 months of ET
      • PIK3CA mut.
        • Palbo + fulvestrant + Inavolisib (INAVO120)
          • PIK3CA, PTEN, AKT alteration
            • Capivasertib + ET CAPItello-291
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
          • ESR1 mut.
            • Elacestrant - EMERALD / Imlunestrant - EMBER-3
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
          • gBRCA 1/2 mut.
            • PARPi (Ola, Tal) OLYMPIAD, EMBRACA
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
          • PIK3CA mut.
            • Alpelisib + ET SOLAR-1, BYLieve
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
      • PIK3CA wt
        • CDK4/6 inhibitor + endocrine therapy
          • PIK3CA, PTEN, AKT alteration
            • Capivasertib + ET CAPItello-291
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
          • ESR1 mut.
            • Elacestrant - EMERALD / Imlunestrant - EMBER-3
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
          • gBRCA 1/2 mut.
            • PARPi (Ola, Tal) OLYMPIAD, EMBRACA
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
          • PIK3CA mut.
            • Alpelisib + ET SOLAR-1, BYLieve
              • None of the above or after progression in 1L lines of therapy from prior
                • Everolimus, AI or Fulvestrant
                  • HER2 null
                    • Chemo
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 ultralow IHC 0
                    • T-DXd*** DESTINY-Breast06
                      • Dato-DXd Tropion Breast 01***
                        • Chemo
                        • Sacituzumab govitecan TROPiCS***
                          • Chemo
                  • HER2 low HER2 1-2+
                    • T-DXd*** DESTINY-Breast06
                      • T-DXd*** DESTINY-Breast 04
                        • Sacituzumab govitecan TROPiCS***
                          • Dato-DXd Tropion Breast 01***
                            • Chemo
                    • Chemo
    • De novo PD, 1L on adjuv or after adjuv ET
      • CDK4/6 inhibitor + endocrine therapy
        • PIK3CA, PTEN, AKT alteration
          • Capivasertib + ET CAPItello-291
            • None of the above or after progression in 1L lines of therapy from prior
              • Everolimus, AI or Fulvestrant
                • HER2 null
                  • Chemo
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 ultralow IHC 0
                  • T-DXd*** DESTINY-Breast06
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 low HER2 1-2+
                  • T-DXd*** DESTINY-Breast06
                    • T-DXd*** DESTINY-Breast 04
                      • Sacituzumab govitecan TROPiCS***
                        • Dato-DXd Tropion Breast 01***
                          • Chemo
                  • Chemo
        • ESR1 mut.
          • Elacestrant - EMERALD / Imlunestrant - EMBER-3
            • None of the above or after progression in 1L lines of therapy from prior
              • Everolimus, AI or Fulvestrant
                • HER2 null
                  • Chemo
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 ultralow IHC 0
                  • T-DXd*** DESTINY-Breast06
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 low HER2 1-2+
                  • T-DXd*** DESTINY-Breast06
                    • T-DXd*** DESTINY-Breast 04
                      • Sacituzumab govitecan TROPiCS***
                        • Dato-DXd Tropion Breast 01***
                          • Chemo
                  • Chemo
        • gBRCA 1/2 mut.
          • PARPi (Ola, Tal) OLYMPIAD, EMBRACA
            • None of the above or after progression in 1L lines of therapy from prior
              • Everolimus, AI or Fulvestrant
                • HER2 null
                  • Chemo
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 ultralow IHC 0
                  • T-DXd*** DESTINY-Breast06
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 low HER2 1-2+
                  • T-DXd*** DESTINY-Breast06
                    • T-DXd*** DESTINY-Breast 04
                      • Sacituzumab govitecan TROPiCS***
                        • Dato-DXd Tropion Breast 01***
                          • Chemo
                  • Chemo
        • PIK3CA mut.
          • Alpelisib + ET SOLAR-1, BYLieve
            • None of the above or after progression in 1L lines of therapy from prior
              • Everolimus, AI or Fulvestrant
                • HER2 null
                  • Chemo
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 ultralow IHC 0
                  • T-DXd*** DESTINY-Breast06
                    • Dato-DXd Tropion Breast 01***
                      • Chemo
                      • Sacituzumab govitecan TROPiCS***
                        • Chemo
                • HER2 low HER2 1-2+
                  • T-DXd*** DESTINY-Breast06
                    • T-DXd*** DESTINY-Breast 04
                      • Sacituzumab govitecan TROPiCS***
                        • Dato-DXd Tropion Breast 01***
                          • Chemo
                  • Chemo
tosprivacyA 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)Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer (MONALEESA-2)Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer. (MONALEESA-3)Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer (MONALEESA-7)A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer (MONARCH 2)A Study of Nonsteroidal Aromatase Inhibitors Plus Abemaciclib (LY2835219) in Postmenopausal Women With Breast Cancer (MONARCH 3)A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/​HER2- Advanced Breast Cancer (PALOMA-2)Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/​HER2- Breast Cancer (CAPItello-291)Phase 3 Trial of Elacestrant Versus Standard of Care for the Treatment of ER+/​HER2- Advanced Breast Cancer (EMERALD)A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3)Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/​2 Mutations. (OlympiAD)A Study Evaluating Talazoparib (BMN 673), a PARP Inhibitor, in Advanced and/​or Metastatic Breast Cancer Patients With BRCA Mutation (EMBRACA Study) (EMBRACA)Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment. (SOLAR-1)Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments (BYLieve)Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06)A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/​HER2- Metastatic Breast Cancer (TROPiCS-02)Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]