The first 60 days: HER2-low and HER2-ultralow metastatic breast cancer
HER2-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. Below, week by week, is what OnCo's record of HER2-low and HER2-ultralow metastatic breast cancer says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
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.
Trastuzumab deruxtecan ahead of chemotherapy for HER2-low or ultralow disease (DESTINY-Breast06).
Trastuzumab deruxtecan for HER2-low disease of either hormone receptor status (DESTINY-Breast04).
TROP2 antibody-drug conjugates first (ASCENT, TROPION-Breast02), trastuzumab deruxtecan as a later option.
Baseline and interval CT, prompt corticosteroids and permanent discontinuation for grade 2 or higher interstitial lung disease.
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.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example HER2 immunohistochemistry score 0, ultralow, 1+ or 2+ with in situ hybridisation for 2+, Retesting on a metastatic biopsy because HER2-low status changes over time, Hormone receptor status, Baseline chest imaging and lung function for interstitial lung disease surveillance, PIK3CA, ESR1 and germline BRCA status to sequence against targeted options), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Hormone receptor-positive HER2-low disease, Hormone receptor-positive HER2-ultralow disease, Triple-negative HER2-low disease.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Hormone receptor-positive, after endocrine therapy, chemotherapy-naive
- For my situation (hormone receptor-positive, after endocrine therapy, chemotherapy-naive), which of the standard options do you recommend and why?Guideline options include: Trastuzumab deruxtecan ahead of chemotherapy for HER2-low or ultralow disease (DESTINY-Breast06).
- Am I a candidate for Trastuzumab deruxtecan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DESTINY-Breast06 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
After one or two lines of chemotherapy
- For my situation (after one or two lines of chemotherapy), which of the standard options do you recommend and why?Guideline options include: Trastuzumab deruxtecan for HER2-low disease of either hormone receptor status (DESTINY-Breast04).
- Am I a candidate for Trastuzumab deruxtecan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of DESTINY-Breast04 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Triple-negative HER2-low disease
- For my situation (triple-negative her2-low disease), which of the standard options do you recommend and why?Guideline options include: TROP2 antibody-drug conjugates first (ASCENT, TROPION-Breast02), trastuzumab deruxtecan as a later option.
- Am I a candidate for Sacituzumab govitecan, Datopotamab deruxtecan, Trastuzumab deruxtecan, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ASCENT and TROPION-Breast02 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Lung toxicity
- For my situation (lung toxicity), which of the standard options do you recommend and why?Guideline options include: Baseline and interval CT, prompt corticosteroids and permanent discontinuation for grade 2 or higher interstitial lung disease.
Any stage
- Are there clinical trials I could join, for example of Trastuzumab deruxtecan, Sacituzumab tirumotecan, Trastuzumab rezetecan, Disitamab vedotin?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Immunohistochemistry was never designed to score low expression and pathologists disagree at the 0 to 1+ boundary”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether a second topoisomerase I payload works after the first”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- 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.
- HER2-low and HER2-ultralow: Tumours with a little HER2 (IHC 1+ or 2+ without amplification), or a trace (ultralow), which older HER2 drugs ignored but Enhertu can attack.
- Interstitial lung disease (ILD) / pneumonitis: Interstitial lung disease (ILD) is lung inflammation, a serious side effect of some ADCs (especially Enhertu) and immunotherapy.
Every term links to the glossary.