One biopsy, one tiny window
A woman with metastatic breast cancer learns she has tumor deposits in her liver, her bones, and her lungs. Her oncologist pulls a biopsy from the most accessible spot — say, a lymph node — and sends it off for HER2 testing.
That single sample decides whether she gets a drug that could extend her life.
But what if the lymph node doesn't match the liver? What if one tumor is HER2-positive and another isn't? A trial now underway in Sweden wants to find out whether a full-body scan can paint a fuller picture.
Why HER2 is such a big deal
HER2 is a protein that sits on the surface of some breast cancer cells. In cancers with a lot of HER2, the protein acts like a stuck accelerator — driving rapid growth.
For years, doctors divided breast cancer into two groups: HER2-positive and HER2-negative. Positive patients got HER2-targeted drugs. Negative patients did not.
Then came a twist. Researchers realized a third group — HER2-low — responded to a new class of drug too. HER2-low means the cancer has some HER2 on its cells, but not a lot.
The drug that changed the game is trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate. Think of it as a smart missile: an antibody that locks onto HER2, carrying a chemotherapy payload that releases inside the cancer cell.
T-DXd works well. But not for everyone. And the current way of predicting who benefits — a single tumor biopsy — is imperfect.
Old way, new way
The standard biomarker is HER2 immunohistochemistry (IHC), a lab test that stains a biopsy slice and scores HER2 levels. It works, but it captures only one spot in one moment.
Cancer is not one spot in one moment. Metastatic cancer spreads, and different deposits can have different biology. One biopsy can miss that picture entirely.
Here's the twist. The new approach skips the single-site limitation by imaging the entire body at once.
The trial uses a tracer called 68GaGa-ABY-025. That is a small protein engineered to bind HER2, tagged with a radioactive isotope.
Patients get injected. The tracer circulates and sticks to HER2 wherever it finds it. A PET/CT scanner then reads the signal across the whole body.
Picture it like a black-light flashlight that lights up every HER2 hotspot at once. Bright lesions glow. Dim ones barely show. Cold ones stay dark.
That is real-time, whole-body HER2 mapping — something a needle biopsy simply cannot do.
What the trial is set up to test
The study, called HER2-Ex PET, is a multicenter phase II trial registered as NCT06830382. It plans to enroll 70 patients.
All participants have HER2-low metastatic breast cancer and are candidates for T-DXd. Every patient gets a baseline HER2-PET scan and a standard tumor biopsy.
Patients with biopsy-confirmed HER2 expression (IHC 1+ or 2+) enter Cohort 1, where they receive T-DXd and get a repeat HER2-PET scan after 3 to 4 cycles. Other patients enter Cohort 2 and receive their doctor's choice of therapy.
The primary question: does the baseline PET signal predict whether the cancer shrinks on T-DXd?
The site at Karolinska University Hospital in Stockholm is already open. Uppsala and Skåne are scheduled to start enrolling in early 2026.
What the researchers are hoping for
If PET signal correlates with T-DXd response, it would mean oncologists could eventually use imaging — not just biopsy — to decide who starts the drug.
That matters for a few reasons. Whole-body imaging picks up differences between tumors in the same patient. It also avoids the risks and discomfort of repeat biopsies, especially from hard-to-reach sites like lung or bone.
This trial has not reported results yet. It is still enrolling. Nothing here is proven.
But the design is thoughtful and the science behind ABY-025 is solid. If the correlation holds, PET-guided T-DXd could become part of standard care within a few years.
An expert lens
Oncology imaging has been shifting this way for a while. Prostate cancer already uses PSMA-PET to guide therapy decisions. Neuroendocrine tumors use gallium-tagged somatostatin scans.
Breast cancer has been slower to adopt functional imaging beyond standard PET-FDG (which tracks metabolism, not specific targets). A HER2-specific tracer would fill an obvious gap.
The bigger theme: cancer care is moving away from treating a biopsy slide and toward treating a whole person with heterogeneous disease.
What this means for you today
If you or someone you love has HER2-low metastatic breast cancer, this trial does not change anything about current care.
T-DXd remains approved based on biopsy results. HER2-PET is not available outside research settings in most countries.
But if you are in Sweden and meet the criteria, the trial is open. Ask your oncologist whether Karolinska, Uppsala, or Skåne might be worth a conversation.
For everyone else, the right move is to keep an eye on how this trial reports — likely in 2027 or later.
The honest limitations
This is a phase II diagnostic study, not a randomized treatment trial. It can show correlation but not prove that PET-guided treatment beats biopsy-guided treatment.
The sample size of 70 is small. It gives 80% statistical power for the primary endpoint but leaves less room for detailed subgroup analysis.
There is also no randomization, which means selection effects are possible.
And biopsies and scans happen at slightly different times, so changes in tumor biology between the two measurements could muddy results.
If HER2-Ex PET produces a strong signal, expect follow-up randomized trials comparing PET-guided versus biopsy-guided T-DXd selection.
The bigger prize is a world where whole-body molecular imaging routinely maps not just HER2 but many tumor targets — turning metastatic cancer care into something far more personalized than it is today.
Right now, we are still at the beginning of that road. But the first mile is being walked in a Stockholm hospital this year.
