Olubukola Ayodele, Breast Cancer Lead at University Hospitals of Leicester NHS Trust, shared a post on LinkedIn:
“Have you heard of the term HER2-low?
If you’ve attended a breast cancer meeting recently, read a journal article, or sat in an oncology clinic, you’ve probably heard it mentioned.
Also, even more recently, you may have heard another term:
HER2-ultralow.
But what do these terms actually mean?
Traditionally, pathology reports classified breast cancers as either:
HER2-positive OR HER2-negative.
HER2-positive cancers could benefit from HER2-directed therapies.
HER2-negative cancers could not.
Simple.
Except biology is rarely that simple.
We now recognise that HER2 exists on a spectrum.
Some cancers previously classified as HER2-negative actually express small amounts of HER2.
Not enough to be considered HER2-positive, but enough to matter.
HER2-low generally includes:
- IHC 1+
- IHC 2+ / ISH negative
HER2-ultralow describes cancers with very faint HER2 expression, many of which may previously have been reported as HER2-0.
So why has this suddenly become important? Because, antibody-drug conjugates challenged that thinking.
For years we asked:
“Is HER2 driving the cancer?”
Today, we are increasingly asking: “Is there enough HER2 present for treatment to reach the cancer cell?”
That is a profound shift.
HER2 does not need to be the driver; it can simply be the doorway.
Trials such as DESTINY-Breast04 and more recently DESTINY-Breast06 have challenged the traditional HER2-positive versus HER2-negative divide and expanded treatment possibilities for many patients.
The biggest lesson extends beyond HER2 itself but that cancer biology is rarely black and white.
The closer we look, the more nuance we find and sometimes, within that nuance, we discover new opportunities.
More options.
More precision.
More HOPE.
HER2-low and HER2-ultralow are not simply new labels. They are reminders that our understanding of cancer continues to evolve, and that what we once called “negative” may not always tell the whole story.
This is precision oncology evolving in real time.
Have HER2-low and HER2-ultralow changed how you think about “HER2-negative” disease?
Have you started discussing HER2-low or HER2-ultralow with your patients or colleagues?”
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