Could some HER2-positive metastatic breast cancers be curable?

If you are diagnosed with metastatic breast cancer, one of the first things you’ll likely hear is that it’s not curable. That understanding has shaped how patients and doctors think about stage IV breast cancer for decades. But for a small group of patients, especially those with HER2-positive disease, the possibility of being treated with curative intent is becoming more of a real possibility.

HER2-positive breast cancer has become one of the biggest success stories in modern oncology. Targeted therapies like trastuzumab and pertuzumab have significantly improved survival, and newer treatments like trastuzumab deruxtecan are pushing outcomes even further. Because of this, some patients are experiencing deep and sustained responses to treatment. In some cases, scans show no visible evidence of disease for long periods of time.

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Twenty-five years ago, HER2-positive metastatic breast cancer was considered one of the most aggressive and deadly forms of the disease. Today, it’s increasingly described as one of the most treatable. One woman, diagnosed with HER2-positive metastatic breast cancer with disease in eleven different sites, including her lungs and liver, began standard treatment with chemotherapy and HER2-targeted therapy. Like most patients, she was told she would likely need to stay on treatment for life. But something unexpected happened. Her cancer responded… and kept responding! Eventually, she reached a point where there was no visible evidence of disease, and years into treatment, she was even offered the option to stop therapy as part of a clinical trial. This kind of outcome would have been almost unimaginable not long ago.

With the introduction of HER2-targeted therapies like trastuzumab and pertuzumab, and now newer drugs like trastuzumab deruxtecan, outcomes have improved dramatically. In long-term follow-up from major trials, a meaningful percentage of patients remain progression-free for many years.  In one cohort, about 15 percent of patients achieved a complete response, and nearly 10 percent remained in remission for more than five years. 

That is where the conversation starts to get uncomfortable for the traditional definition. Because when a patient has no evidence of disease for five, seven, even ten years, the line between “controlled” and “cured” begins to blur. Some oncologists are now willing to say that out loud:

“We believed that HER2-positive metastatic breast cancer should no longer be considered an incurable disease, but an occasionally curable disease,” said medical oncologist John Crown, reflecting on these long-term outcomes.

Others are more cautious, but still acknowledge the shift.

“Historically, every textbook on HER2-positive metastatic breast cancer has defined the disease as incurable. But that understanding is shifting. We are beginning to see patients achieve such profound, long-term disease control that it no longer limits their life expectancy—and in a few exceptional cases, we may even be talking about a cure,” said Joseph Gligorov, a professor of medical oncology in Paris.

While hopeful, this line of thinking raises new and difficult questions for patients. If some patients are achieving long-term remission, how do we identify who they are? If treatment can be stopped in certain cases, when is it safe to do so? For now, there are no simple answers, but researchers are actively studying these “exceptional responders” to understand what makes them different. Some studies are looking at genetic features of tumors. Others are testing whether treatment strategies can be adjusted to increase the number of patients who achieve deep, durable responses. 

While advancements are encouraging, the idea of cure in metastatic breast cancer is still the exception, not the expectation. But the fact that we are even asking the question in certain patients is a sign of real progress. And when things are changing at this pace, patients deserve to understand not just today’s standard, but what’s being explored for tomorrow.

At Outcomes4Me, we believe patients deserve to understand not just what is standard today, but what is changing. Our app helps you make sense of your specific subtype, your treatment options, and the clinical trials exploring what’s next, all grounded in evidence and tailored to you.