HER2+ Breast Cancer

Authored by Ilana Schlam, published on 2026-04-12 17:02:19.0

HER2+ Breast Cancer treatment algorithm updated with the latest from ASCO, ESMO and SABCS 2025 data.

  1. Early stage HER2+
    • <2 cm and node negative
      • Surgery
        • pT1pN0
          • Weekly TH x 12
            • Complete 1 year of trastuzumab
        • pT2 or pN1 +
          • Adjuvant chemotherapy with trastuzumab +/- pertuzumab
            • Complete 1 year of trastuzumab +/- pertuzumab
    • >2 cm or node positive
      • Neoadjuvant chemotherapy with trastuzumab and pertuzumab
        • Surgery
          • pCR
            • Complete 1 year of trastuzumab +/- pertuzumab
          • RD
            • Complete 1 year of TDM1
              • Consider 1 year of neratinib
  2. Advanced HER2+ disease
    • No CNS involvement
      • THP → HP ( with endorine therapy if HR+. Consider palbo or tucatinib maintenance -not FDA approved) or TDXd +/- P
        • T-DXd (if TDXd not used 1L)
          • TDM1
            • Trastuzumab + chemotherapy
          • Tucatinib, trastuzumab, capecitabine
            • Neratinib + capecitabine
            • Lapatinib + capecitabine
            • Margetuximab + chemotherapy
    • CNS involvement
      • THP → HP ( with endorine therapy if HR+. Consider palbo or tucatinib maintenance -not FDA approved) or TDXd +/- P
        • T-DXd (if TDXd not used 1L)
          • TDM1
          • Tucatinib, trastuzumab, capecitabine
            • Trastuzumab + chemotherapy
            • Neratinib + capecitabine
            • Lapatinib + capecitabine
            • Margetuximab + chemotherapy
tosprivacyAdjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trialAdjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trialLong-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancerSurvival with Trastuzumab Emtansine in Residual HER2-Positive Breast CancerOverall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trialPertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 studyTrastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trialTrastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trialTucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysisTrastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trialNeratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA TrialMargetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial