The first 60 days: HER2-low and HER2-ultralow metastatic breast cancer

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.

• RadiologistNamed in the standard of care for: Lung toxicity.
• Medical oncologistNamed in the standard of care for: Hormone receptor-positive, after endocrine therapy, chemotherapy-naive, After one or two lines of chemotherapy, Triple-negative HER2-low disease.

A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.

Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.

1. 1.Hormone receptor-positive, after endocrine therapy, chemotherapy-naive

   Trastuzumab deruxtecan ahead of chemotherapy for HER2-low or ultralow disease (DESTINY-Breast06).

   Trastuzumab deruxtecanDESTINY-Breast06HER2-low and HER2-ultralow
2. 2.After one or two lines of chemotherapy

   Trastuzumab deruxtecan for HER2-low disease of either hormone receptor status (DESTINY-Breast04).

   Trastuzumab deruxtecanDESTINY-Breast04HER2-low and HER2-ultralow
3. 3.Triple-negative HER2-low disease

   TROP2 antibody-drug conjugates first (ASCENT, TROPION-Breast02), trastuzumab deruxtecan as a later option.

   Sacituzumab govitecanDatopotamab deruxtecanASCENTTROPION-Breast02Trastuzumab deruxtecan
4. 4.Lung toxicity

   Baseline and interval CT, prompt corticosteroids and permanent discontinuation for grade 2 or higher interstitial lung disease.

   CT (computed tomography)Interstitial lung disease (ILD) / pneumonitis

Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.

Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.

• A Clinical Trial of TQB2102 for Injection in the Treatment of HER2 Low-Expressing Recurrent/Metastatic Breast CancerPhase 3 · active · NCT06561607A Randomized, Open, Parallel-Controlled Phase III Clinical Trial Evaluating the Efficacy and Safety of TQB2102 for Injection Versus Investigator-Selected Chemotherapy in HER2 Low-Expressing Recurrent/Metastatic Breast Cancer
• A Study of DB-1303/BNT323 vs Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Metastatic Breast Cancer (DYNASTY-BrePhase 3 · active · NCT06018337A Phase 3, Randomized, Multi-center, Open-Label Study of DB-1303 Versus Investigator's Choice Chemotherapy in Human Epidermal Growth Factor Receptor 2 (HER2)-Low, Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy (ET) (DYNASTY-Breast02)
• JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer SubjectsPhase 3 · recruiting · NCT06079983A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial Of JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
• Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer Who Have Received Endocrine TherapyPhase 3 · active · NCT05840211A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Hormone Receptor-Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) (HER2 IHC0 or HER2-low [IHC 1+, IHC 2+/ISH-]) Inoperable, Locally Advanced, or Metastatic Breast Cancer and Have Received Endocrine Therapy
• Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast CancerPhase 3 · recruiting · NCT05950945A Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer (DESTINY-Breast15)

Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.

• Free in oncologyFree testing, helplines, rides and lodging, second opinions and trial travel help, with who is eligible.
• Financial helpManufacturer programmes, national schemes and charities by country and product.
• Second opinionExpert centres for this cancer in your country and how referral works.

• HER2-low and HER2-ultralow metastatic breast cancer: the full pageHER2-low is not a new kind of breast cancer but a new way of reading an old test: tumours once called HER2-negative that carry a little HER2 protein. That trace is enough for the antibody-drug conjugate trastuzumab deruxtecan to deliver its chemotherapy payload, and since 2022 it has been the standard for these patients after endocrine therapy or a first chemotherapy.
• One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
• Treatment sequencingWhich treatment tends to follow which, line by line.
• NavigatorStandard of care for your stage, what you have tried, and trials near you.