A New Breast Cancer Classification Could Change Your Treatment Options

If you have a breast cancer diagnosis, there's a recently identified category that may make you eligible for a new therapy that may be the right option for you.  Keep reading to find out if this drug could work for your specific type of breast cancer.

Breast cancer research moves fast. That means new treatments are emerging and researchers are getting better at matching the right therapy to the right patient. But it also means that what your oncologist told you two years ago might not reflect what's possible today. 

One of the most significant recent developments is a new breast cancer subtype called HER2-ultralow. If you have a breast cancer diagnosis, especially if you've been told your cancer is "HER2-negative," this is worth knowing about. 

What is HER2? 

HER2 stands for Human Epidermal growth factor Receptor 2. HER2 is a protein on the surface of cells. In healthy tissue, it helps cells grow and divide normally. In some breast cancers, the gene that produces HER2 goes haywire and the cancer cells make too much of it. When overproduction of HER2 happens, those cells tend to grow more aggressively. 

When doctors say a cancer is "HER2-positive," they mean that the tumor has an unusually high amount of this protein. 

For a long time, the classification was simple: you were either HER2-positive or you weren't. However that spectrum has started to change, impacting therapies available to patients. 

The HER2 spectrum: from positive to negative, and everything in between 

Pathologists measure HER2 expression using a scoring system that runs from 0 to 3+: 

• 3+ (HER2-positive): High HER2 expression. Standard HER2-targeted therapies apply. 

• 2+ (amplified): Also considered HER2-positive after additional testing confirms amplification. 

• 2+ (not amplified) and 1+: Until recently, these patients were grouped with HER2-negative and weren’t offered HER2-targeted therapies. 

• 0: No detectable HER2 expression. 

A few years ago, researchers recognized a meaningful difference between patients who scored 1+ or 2+ (non-amplified) and those who scored a true 0. They gave the 1+ and 2+ group a new name: HER2-low. 

Then researchers looked even closer and found something else. Some patients scored as HER2 0 had faint but detectable HER2 expression that wasn't quite 1+, but wasn't nothing either - it was 0+.

This is the group now called HER2-ultralow.

Why does HER2-ultralow matter? The Enhertu connection. 

A drug called Enhertu (scientific name: fam-trastuzumab deruxtecan-nxki, or T-DXd) has shown strong effectiveness in treating certain breast cancers. It's an antibody-drug conjugate (ADC), which means it's a targeted therapy that delivers chemotherapy directly to cancer cells that express HER2, while leaving healthy cells alone. 

Enhertu was initially approved by the FDA for HER2-positive patients. Then trials (Destiny-Breast) showed it also worked in HER2-low patients. That was a significant expansion – a large group of patients who had previously been excluded became eligible. 

Now, we have clinical trial data that shows that Enhertu is a valuable therapy in HER2-ultralow patients. 

How something called “real-world evidence” can be important to advancing our understanding of HER2-ultralow breast cancer - and what it might mean for you. 

HER2-ultralow is a relatively new way of classifying breast cancer, one that didn't really exist as a distinct category until recent years. Patients with very low levels of HER2 protein expression were previously grouped in with "HER2-negative" patients, even though we now know that distinction matters for treatment response. Enhertu's approval for this group was based on clinical trials, but real life looks different. 

Patients vary in age, other health conditions, prior treatments, and everyday circumstances in ways no single trial can fully capture. Because HER2-ultralow is such a newly defined category, there's especially limited real-world evidence on how Enhertu performs once it moves from the trial setting into everyday practice, evidence that can only come from the patients actually living this diagnosis.

That's the role of a patient registry: gathering real-world experiences directly from patients so researchers can build a fuller picture over time. For HER2-ultralow specifically, that means researchers can:

• See whether Enhertu performs as well in everyday practice as it did in clinical trials
• Understand how it affects a broader range of patients than any single trial could include
• Learn more about the side effects and day-to-day experiences patients actually have

The patients who stand to benefit most from this research are the same ones who can help create it. That includes you, if you have or have had a breast cancer diagnosis.

"How do I know if I'm HER2-ultralow?" 

You might not know yet, and your health portal might not say it explicitly. The term "HER2-ultralow" is recent enough that many older reports don't use it. You might have a score of 0 on paper. But whether that's a true zero or a faint positive that qualifies as ultralow depends on the specifics of how the test was read. 

If you want to find out where you stand, here's what to do: 

1. Locate your pathology report. You have a legal right to request it from the hospital or lab where your biopsy or surgery was performed. 

2. Look for your HER2 score. It will typically be listed as 0, 1+, 2+, or 3+, sometimes with a note about whether amplification was detected. 

3. Ask your oncologist about HER2-ultralow. If you scored 0, ask specifically whether your result might qualify as ultralow under the newer criteria. 

Questions to bring to your next oncology appointment 

• "Was my HER2 score a true zero, or could it fall into the ultralow range?" 

• "Has my pathology been re-reviewed against the newer HER2-ultralow criteria?"

• "Are there registries or studies I should know about for my specific subtype?"

•"Is Enhertu something I should be asking about at this stage?" 

Why this is worth your attention 

If you've been told HER2-targeted therapies aren't an option for you, HER2-ultralow is a classification that could change what's available. 

This is one of the reasons the HER2UL registry matters. Participating often involves sharing your pathology report and other records, which lets researchers review your HER2 score against the new classification criteria, and better understand which therapies are available to patients.

About Novellia: Novellia is a patient health platform that helps people consolidate their medical records, understand their health data, and participate in research studies on their own terms. Patients stay in control of their data at every step.