Breast cancer ribbon transforming into a HER2 receptor

HER2 and Breast Cancer Recurrence: What You Need to Know

Elliot Brynn in Health & Wellness December 2025 • 4 min read.

"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.

HER2 Expression: A Closer Look at Concordance

Breast cancer ribbon transforming into a HER2 receptor

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+.

Here’s what they found:

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.

These findings suggest that while HER2 expression is generally consistent, it can change in some cases. This has important implications for treatment planning.

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.

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.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.3892/etm.2011.335, Alternate LINK

Title: Human Epidermal Growth Factor Receptor 2 Protein Expression Between Primary Breast Cancer And Paired Asynchronous Local-Regional Recurrences

Subject: Cancer Research

Journal: Experimental and Therapeutic Medicine

Publisher: Spandidos Publications

Authors: Jianjie Xiang, Xiaochan Pan, Jing Xu, Xianhua Fu, Dongping Wu, Yu Zhang, Li Shen, Qichun Wei

Published: 2011-01-01

Everything You Need To Know

What is HER2, and why is it important in breast cancer?

HER2, or human epidermal growth factor receptor 2, is a protein that, when overexpressed, can promote the growth of breast cancer cells. Identifying HER2 expression is crucial because targeted therapies like trastuzumab (Herceptin) are effective against HER2-positive breast cancers, significantly improving treatment outcomes. Understanding HER2 status helps doctors select the most appropriate and effective treatment strategies. While the text focuses on local-regional recurrences, HER2's role extends to metastatic disease as well. Testing for HER2 is typically done via immunohistochemistry or FISH (fluorescence in situ hybridization).

How often does HER2 expression change when breast cancer recurs locally?

In local-regional recurrences, HER2 expression is generally consistent with the primary tumor. A recent study found a high level of agreement (85.71%) in HER2 overexpression between primary tumors and their local-regional recurrences. However, there is discordance in 14.28% of cases, meaning the HER2 status had changed. These findings suggest that while HER2 expression is typically stable, reassessment at recurrence is important to confirm HER2 status and guide treatment decisions.

If HER2 status changes during a local-regional recurrence, what is the most common type of change observed?

When HER2 status changes during a local-regional recurrence, the most common change observed is a decrease in HER2 expression. Specifically, tumors that initially showed a 2+ score in the primary tumor tend to become 0 or 1+ in the recurrence. It's less common for tumors to increase in HER2 expression from a lower score in the primary tumor to a higher score in the recurrence. Notably, tumors that were 3+ in the primary lesion remained 3+ in the recurrence, indicating stability in high HER2 expression.

How does HER2 status in local-regional recurrence affect treatment decisions for breast cancer patients?

The HER2 status in local-regional recurrence is very important for treatment decisions. If the recurrence maintains HER2 overexpression (2+ or 3+), HER2-targeted therapies like trastuzumab (Herceptin) may still be effective. However, if the HER2 status changes to negative (0 or 1+), these targeted therapies may no longer be appropriate, and alternative treatment strategies need to be considered. This is why retesting HER2 expression at the time of recurrence is crucial to ensure patients receive the most effective treatment.

What are the broader implications of understanding HER2 expression in both primary breast cancers and local-regional recurrences for precision medicine?

Understanding HER2 expression in both primary breast cancers and local-regional recurrences is crucial for precision medicine because it allows for tailored treatment strategies. Consistent HER2 expression supports the continued use of HER2-targeted therapies, while changes in HER2 status necessitate adjustments in treatment plans. This individualized approach maximizes treatment efficacy and minimizes unnecessary exposure to ineffective therapies. The study underscores the importance of reassessing biomarker status at recurrence, guiding clinicians in making informed decisions and improving outcomes. Future research could explore the mechanisms driving HER2 status changes and investigate novel therapeutic targets for HER2-negative recurrences.