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5 September 2008
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HER-2-overexpressing breast tumors may switch in response to therapy
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MedWire News: Breast cancer patients who overexpress the human epidermal growth factor receptor (HER)-2 and are treated with monoclonal antibody therapy may actually convert to HER-2-negative status during treatment, study findings show.
"It's known that a small percentage of HER-2 positive patients develop a resistance during treatment, and there have been several described mechanisms," said study co-author Elizabeth Mittendorf (The University of Texas MD Anderson Cancer Center, Houston, USA) presenting the findings at the recent 2008 Breast Cancer Symposium in Washington, D.C.
The researchers say they may have uncovered a new resistance mechanism through their work; alternatively, among patients who converted, HER-2-positive disease may have been eradicated allowing HER-2-negative disease to proliferate.
Using the MD Anderson Breast Medical Oncology database, the team identified 143 breast cancer patients, all of whom had tumors that overexpressed HER-2 at the time of diagnosis. The women were treated with HER-2 monocloncal antibody treatment, in combination with taxane- and anthracycline-based chemotherapies, prior to surgery.
At the time of surgery, 50% of all patients achieved a pathologic complete response (pCR). Of those who did not achieve pCR, pre- and post-treatment tissue samples were available for 23 patients which were analyzed using FISH, a laboratory technique that uses fluorescent probes to detect specific DNA sequences, in this case, additional copies of the HER-2 gene. Seven patients, or 30.4%, were found to be HER-2 negative at the time of surgery.
With a median follow-up of 10.2 months, the researchers also found that two patients (2.8 %) who had achieved a pCR had recurred, compared with eight patients (11.3%) who did not achieve a pCR. Of the second group, tumor samples were available for five; three had converted to HER-2-negative status.
"At this stage, I think the findings advocate for reassessing HER-2 status at the time of surgery," said study co-author Ana Gonzalez-Angulo, also from the MD Anderson Cancer Center.
She added: "However, it would be inappropriate for clinicians to conclude from our study that women with a change in HER-2 status should not receive their full course of [anti-Her-2 therapy] therapy.
The team concluded: "Certainly, the study warrants further investigation of what might be the best adjuvant therapy for this sub-set of women and suggests that a clinical trial in the adjuvant setting would be appropriate."
The 2008 Breast Cancer Symposium; Washington, DC, USA; 5-7 September
http://www.asco.org/ASCO/Meetings/ASCO+Symposia+%26+Workshops/The+Breast+Cancer+Symposium
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