ASCO Breast: HER2 Conversion Linked to Incomplete Response to Trastuzumab (Herceptin)
WASHINGTON, Sept. 4 (MedPage Today) -- Almost a third of incomplete responses to trastuzumab (Herceptin) may involve breast tumors that convert from HER2-positive to negative status, according to a study reported here.
Comparison of pre- and posttreatment tissue specimens showed that 30.4% of initially HER2-positive tumors that failed to have a pathologic complete response converted to HER2-negative status during treatment.
"We don't yet know, on a molecular level, what causes tumors to change," Elizabeth A. Mittendorf, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, said at a press briefing preceding the 2008 Breast Cancer Symposium.
The HER2 conversion is the only distinguishing feature of the tumors identified so far, she added.
Various studies have shown that rates of pathologic complete response to trastuzumab top out at about 60%, leaving a substantial number of patients with residual breast cancer. Speculation about the reasons for incomplete response has included the possibility that some HER2-positive tumors stop expressing HER2/neu during treatment.
Dr. Mittendorf presented findings from a study of 143 patients whose breast cancers initially tested positive for HER2/neu by fluorescence in situ hybridization (FISH). All the patients received neoadjuvant therapy consisting of a taxane, an anathracycline, and trastuzumab.
Reassessment of tumors after neoadjuvant therapy showed that half the patients had pathologic complete responses, defined as no evidence of disease in the breast or axilla.
Pre- and posttreatment tissue specimens were available for 23 patients who had less than pathologic complete response to neoadjuvant therapy. Repeat assessment by FISH confirmed that all specimens were HER2-positive prior to treatment.
Analysis of the posttreatment specimens showed that seven (30.4%) no longer overexpressed HER2/neu.
During a median follow-up of 10.2 months, tumors recurred in two patients (2.8%) who had pathologic complete responses versus eight patients (11.3%) who had less than pathologic complete response.
Analysis of specimens from four patients who had less than pathologic complete response showed that two had converted to HER2-negative status.
Dr. Mittendorf said the findings indicate a need for reassessment of initially HER2-positive tumors that have less than a pathologic complete response to trastuzumab-containing neoadjuvant therapy. Recommendations for adjuvant therapy need to be evaluated in that subgroup of patients, she added.
Dr. Mittendorf reported no potential conflicts of interest relevant to the study.
Primary source: 2008 Breast Cancer Symposium Source reference: Mittendorf EA, et al "Determination of HER2 status in patients achieving less than a pathologic complete response following neoadjuvant therapy with combination chemotherapy plus trastuzumab" Breast Cancer Symposium 2008; Abstract 150.
What breastcancer.org says about this article…
ASCO Breast: HER2 Conversion Linked to Incomplete Response to Trastuzumab (Herceptin)
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. The study reviewed here 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.