If Cancer Stops Responding to Herceptin, It May Have Switched From HER2-Positive to HER2-Negative

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Herceptin (chemical name: trastuzumab) is a targeted therapy used to treat HER2-positive breast cancers. HER2-positive cancers have too many copies of the HER2/neu gene that makes too much of the HER2 protein. About 1 out of every 4 breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive than HER2-negative breast cancers.

Sometimes HER2-positive breast cancers don't respond to Herceptin or stop responding after a while. A study found that about one-third of HER2-positive breast cancers that stop responding or don't respond to Herceptin may do so because the cancers change from being HER2-positive at diagnosis to HER2-negative during treatment. The study was reported during the 2008 American Society of Clinical Oncology (ASCO) Breast Cancer Symposium.

The small study looked at 143 women diagnosed with HER2-positive breast cancer. All of the women received two types of chemotherapy, a taxane and an anthracycline, as well as Herceptin before surgery. Treatment before surgery is called neoadjuvant therapy.

The cancers in about half of the women responded completely to the chemotherapy and Herceptin. This means that after chemotherapy and Herceptin no cancer was found in the breast or the underarm (axillary) lymph nodes during surgery.

The cancers in the other half of the women didn't completely respond to chemotherapy and Herceptin. This means that after chemotherapy and Herceptin cancer was found in the breast or in the underarm lymph nodes during surgery. The researchers analyzed the cancer found during surgery and discovered that in about one-third of the women (30.4%) the cancer wasn't HER2-positive anymore -- it had changed from HER2-positive at diagnosis to HER2-negative some time while the women were receiving chemotherapy and Herceptin.

The researchers followed the women for about 10 months after surgery:

  • 11.3% (eight women) of the women who didn't have a complete response to chemotherapy and Herceptin had the breast cancer come back
  • 2.8% (two women) of the women who had a complete response to chemotherapy and Herceptin had the breast cancer come back

In two of the women who didn't have a complete response to chemotherapy and Herceptin, cancer found during surgery was still HER2-positive, but eventually changed to HER2-negative when the cancer came back.

Abnormal genes give breast cancer cells the ability to grow, divide, and spread uncontrollably. The abnormal genes that make cells cancerous also make them more likely to have still more abnormal genetic changes. This partly explains why breast cancer treatments stop working and why everyone doesn't get the same benefits from a treatment.

The cancer tissue sample taken at the time of diagnosis provides important information that helps you and your doctor make treatment decisions. This information is in your pathology report. Still, a pathology report is a snapshot of the cancer at that time. Breast cancer cells can change over time, both during and after treatment. Cancers can become resistant to treatment or more aggressive. A lot of cancer research is looking at this problem. A better understanding of the changes that cancer cells undergo during treatment and over time will help doctors to develop better, "smarter" treatments that will slow these changes or work in spite of them.

It's not clear exactly how this study will affect breast cancer care. If you're being treated for breast cancer and some cancer remains or comes back after your initial treatments, ask your doctor about the value of testing this tissue and how that might influence your treatment plan. Together, you and your doctor can decide what is best for you and your unique situation.

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