The short answer
NCI advises documenting metastatic breast cancer with a sample and retesting ER, PR and HER2 at that point. Receptors can differ from the first tumor, and the drug list follows the new result.
Ask for a biopsy of a metastatic site with ER, PR and HER2 retested, because receptors can change.
HER2 is now scored in bands: low means 1+, or 2+ with negative in situ hybridization; ultralow means 0 with some membrane staining.
For ER-positive disease NCI describes endocrine therapy with a CDK4/6 inhibitor: palbociclib, ribociclib or abemaciclib.
PIK3CA, AKT1, PTEN, ESR1 and BRCA results each unlock a different named drug, so ask which tests were sent.
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The full explanation.
Re-test the cancer, do not assume
This is the first thing to ask for, and it is easy to miss.
NCI advises that metastatic disease should be documented with a sample, and that ER, progesterone receptor and HER2 should be tested again at that point, when possible.
Receptors can differ from your original breast tumor. Treatment follows the new result, not the old one.
HER2 is no longer a yes or no
The categories have grown. NCI describes a trial that enrolled people with low HER2 expression and with ultralow HER2 expression.
Low means a score of 1+, or 2+ with a negative in situ hybridization result. Ultralow means a score of 0 with some membrane staining.
Those groups received trastuzumab deruxtecan. So the exact wording on your HER2 report matters. Ask for the number, not the word.
Hormone receptor positive disease and its blockers
For ER-positive cancer, NCI describes endocrine treatment given with a CDK4/6 inhibitor. The three are palbociclib, ribociclib and abemaciclib.
Several mutations open extra doors. NCI links alpelisib to PIK3CA, capivasertib to the PIK3CA, AKT1 and PTEN pathway, and elacestrant to ESR1 variants.
ESR1 changes cause resistance to aromatase inhibitors. Finding one is useful information, not bad news alone.
BRCA testing changes the drug list
NCI describes olaparib and talazoparib in breast cancer. Both are PARP inhibitors tied to BRCA changes.
Germline testing also affects your relatives. Ask for genetic counseling alongside the test, not after it.
Questions for the oncology team
- Will you biopsy a metastatic site and recheck ER, PR and HER2?
- What is my exact HER2 score, and does it count as low or ultralow?
- Would you start an aromatase inhibitor or fulvestrant, and which CDK4/6 inhibitor with it?
- Has my tumor been tested for PIK3CA, AKT1, PTEN and ESR1?
- Should I have germline BRCA testing, and what would a result mean for my family?
- I have bone metastases. Do I need a bone-strengthening drug such as zoledronic acid or denosumab?
- One spot is causing pain. Could surgery or radiation treat that spot on its own?
Treating one troublesome spot
NCI lists surgery and radiation for people with limited symptomatic metastases. Bone-modifying therapy is listed for people with bone metastases.
These are part of the plan, not a sign the plan has failed.
When to get help sooner
- Call 911 or go to an emergency department if your legs feel weak or numb, you are unsteady on your feet, or you are losing control of your bladder or bowel. Cancer in the spine can press on the spinal cord, and the damage can become permanent if it is left. Go too for a seizure, sudden weakness on one side, or the worst headache of your life, and for severe breathlessness or chest pain.
- Call your care team the same day if you have new back pain around the spine, especially pain that wraps around like a band or is worse when you lie flat. That pain often comes before any weakness. Call the same day for a swollen painful calf, and for heavy thirst with confusion, drowsiness or constipation, which can mean a high calcium level from bone metastases.
- Ring your oncology team without delay, at any hour, if a temperature of 100.4°F (38°C) or higher shows up while you are on chemotherapy. CDC treats a fever during chemotherapy as a medical emergency. If the line does not get you a person quickly, go to an emergency department and say you are having cancer treatment.
- Call your care team within a day or two if bone pain is climbing and your painkillers are no longer holding it, or if a new cough, ankle swelling or steady breathlessness is building over days.
Related pages
Go deeper: Cancer Staging, Biomarker Testing, Clinical Trial vs Standard Treatment, and Palliative Care.
Where this comes from
Words to know
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Common questions
Why biopsy again if the breast cancer is already known?
NCI advises documenting metastatic disease with a sample and retesting ER, progesterone receptor and HER2 when possible. Those results can differ from the original tumor, and treatment follows the new ones.
What does HER2-low or HER2-ultralow mean?
Low means a score of 1+, or 2+ with a negative in situ hybridization result. Ultralow means a score of 0 with some membrane staining. NCI describes a trial in which both groups received trastuzumab deruxtecan, so ask for your exact score.
Does having bone metastases mean the plan has failed?
No. NCI lists bone-modifying therapy for bone metastases, and surgery or radiation for limited symptomatic spots, as standard parts of metastatic treatment.
Questions to ask your doctor
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Sources last checked: 2026-08-11 what this meansLast updated: 2026-08-19Next planned review: 2027-07-30
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How this page was created
Cancer Explained does not originate medical claims. Every page restates guidance already published by the National Cancer Institute, the CDC, the USPSTF and the FDA, in plain language, with the source cited so you can check the original yourself. AI does the translating and organizing; automated checks test claims, citations, clarity and safety before anything publishes. We do not employ clinicians and do not intend to — our work is translation and navigation, not clinical judgment. Nothing here is personal medical advice, and no page can account for your particular situation.
Editorial status: Source checked — This page was written with AI assistance and checked line by line against the sources listed on it. That confirms the sources support what the page says. It is not a medical review, and it does not confirm the page is complete or right for your situation.
Human medical review: not completed. Pages here are not signed off by a clinician before they publish. That is not an oversight we are quietly working around: we restate published guidance and cite it, so the authority belongs to the source rather than to us, and every page names where its claims come from — you can verify us instead of trusting us. Where a volunteer clinician has reviewed a page, their name and credentials appear on it; where no name appears, no clinician has checked it. We are glad to have reviewers and are recruiting them, and we do not hold pages back waiting for one. Use this site to understand your situation and to ask better questions of the people treating you.
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