HER2 and Breast Cancer Recurrence: What You Need to Know
"Understanding HER2 expression can lead to more effective treatment strategies."
For women battling breast cancer, understanding the characteristics of their tumors is critical. One important factor is the expression of human epidermal growth factor receptor 2, or HER2. HER2 is a protein that can promote cancer cell growth when overexpressed. Targeted therapies like trastuzumab (Herceptin) have revolutionized treatment for HER2-positive breast cancers. But what happens when breast cancer recurs? Does HER2 expression stay the same, and how does this impact treatment decisions?
While we know HER2 expression in the initial tumor is important, less is known about HER2 in local-regional recurrences – when the cancer comes back in the same area. Since receptor characteristics can change over time, it's critical to understand if a recurrence has the same HER2 profile as the original tumor. This information can guide treatment choices and improve outcomes.
A recent study investigated HER2 expression in primary breast cancers and their corresponding local-regional recurrences. The aim was to determine if HER2 status remains stable during the recurrence process.
Why Recurrence Matters
HER2 status is one factor doctors consider when evaluating breast cancer recurrence risk and treatment options. Recurrence can vary widely between individuals, so follow-up care and treatment decisions are personalized. Ongoing research continues to refine how clinicians assess and manage that risk.
Testing and Treatment Limits
Traditional approaches have generally divided breast cancers into HER2-positive and HER2-negative categories, but emerging evidence suggests that treatment responses can vary according to the level of HER2 protein expression. The College of American Pathologists notes that HER2 immunohistochemistry assays were designed mainly to distinguish high protein overexpression caused by gene amplification from tumors without overexpression, rather than to accurately distinguish lower expression levels. Real-world treatment patterns may also differ by recurrence risk, and a January 2026 report said that nearly two-thirds of patients with HER2-positive metastatic breast cancer did not receive the standard THP regimen, often because of age or disease recurrence. Patients who received THP had better outcomes in that report, including longer progression-free survival.
How Recurrence Risk Evolved
Research has identified tumor size, nodal status at diagnosis, and residual cancer after neoadjuvant therapy as important determinants of relapse risk in HER2-positive, hormone-receptor-positive early breast cancer. In early-stage breast cancer overall, HER2 overexpression occurs in about 15% to 20% of patients. One study reported that, without HER2-targeted therapy, 30% to 50% of patients relapse within 10 years, with many developing incurable metastatic disease. Research has also emphasized that HER2 expression can change between the primary tumor and a recurrence, making reassessment potentially important for clinical management.
HER2 Expression: A Closer Look at Concordance
The study, published in Experimental and Therapeutic Medicine, examined HER2 expression in 35 paired samples of primary breast cancers and local-regional recurrences. Researchers used immunohistochemistry to score HER2 expression as 0, 1+, 2+, or 3+. Overexpression was defined as a score of 2+ or 3+.
- HER2 overexpression was present in 48.57% of primary breast cancers and 45.71% of local-regional recurrences.
- There was a high level of agreement (85.71%) in HER2 overexpression between primary tumors and recurrences.
- However, 14.28% of cases showed discordance, meaning the HER2 status had changed.
- In most discordant cases, tumors that were 2+ in the primary tumor became 0 or 1+ in the recurrence. The reverse was rare.
- Importantly, tumors that were 3+ in the primary lesion remained 3+ in the recurrence.
New Research Directions
A 2026 study using heterogeneous HER2 breast cancer models found that HER2-low cells could drive resistance to HER2-targeting antibody-drug conjugates and accelerate recurrence by cooperating with HER2-high cells. The researchers identified therapeutic strategies intended to sensitize HER2-low cells to trastuzumab deruxtecan, or T-DXd. These findings provide mechanistic insight, but model-based results still require clinical evaluation before they can guide routine patient care.
Why Outcomes Still Vary
HER2-directed care has improved outcomes for many patients, but recurrence remains possible and treatment results are not uniform. Differences in tumor biology, HER2 expression, disease risk, treatment access, and treatment tolerance may affect outcomes. These uncertainties support continued monitoring and individualized clinical decision-making rather than assuming that one treatment pathway fits every patient.
Risk Perception and Choices
A 2025 survey found that most patients with non-metastatic cancer were willing to change their dietary habits and exercise routines to reduce recurrence risk. Many respondents also said they would accept additional breast cancer treatment and undergo additional surgery for that purpose. These findings highlight how patients may weigh recurrence prevention against the burdens of further intervention.
What This Means for Breast Cancer Patients
The study confirms that HER2 expression is commonly found in breast cancer and that its expression tends to remain consistent between primary tumors and local-regional recurrences. This is reassuring for patients who initially respond to HER2-targeted therapies.
Putting Recurrence in Context
HER2-positive breast cancer recurrence is influenced by tumor characteristics, treatment response, and changes in HER2 expression over time. Current evidence supports risk-adapted care rather than a single prediction for every patient. Ongoing research may improve testing and help match treatments more precisely to individual disease biology.
The Next Research Questions
Future progress will depend on improving how breast cancer subtypes are identified and how recurrence risk is estimated. Healthline reports that fewer than 20% of breast cancers are HER2-positive and emphasizes that breast cancer comprises multiple diseases with different behaviors. Research into more precise classification and treatment selection may help extend the benefits of HER2-directed care.
Beyond Tumor Biology
Recurrence outcomes are shaped not only by tumor biology but also by access to testing, treatment, follow-up, and supportive care. Differences in age, disease recurrence, and other clinical circumstances can affect whether patients receive standard treatment. Addressing these broader barriers is an important part of improving care.
Care in Real-World Settings
The weekly paclitaxel and trastuzumab APT regimen is described as standard treatment for most patients with stage I HER2-positive breast cancer, based on the single-arm phase II APT trial. Real-world follow-up studies have examined treatment coverage, long-term outcomes, prognostic factors, and recurrence patterns among patients receiving adjuvant trastuzumab. Research using electronic health records has also examined changes in HER2 expression over time, which may matter for personalized treatment decisions.
However, the finding that HER2 status can change in approximately 10% of recurrences highlights the importance of re-evaluating HER2 expression at the time of recurrence. If the HER2 status has changed, a different treatment strategy may be necessary.
While trastuzumab and similar drugs have greatly improved outcomes for HER2-positive breast cancer, they are not effective for HER2-negative cancers. Assessing HER2 status in both the primary tumor and any recurrences ensures that patients receive the most appropriate and effective treatment.