CHANGES IN HER-2 STATUS DURING TREATMENT

Change in HER2 Status May Explain Resistance to Trastuzumab

Zosia Chustecka

Medscape Medical News 2008. © 2008 Medscape

September 9, 2008 — Some women with HER2-positive breast cancer who initially respond well to trastuzumab (Herceptin, Roche/Genentech) eventually stop responding to the drug. Why this happens is unclear, but a new study offers a possible explanation. Trastuzumab works only on HER2-positive tumors, but the study found that during therapy, some tumors convert from HER2-positive to HER2-negative status.

The finding was reported at the 2008 Breast Cancer Symposium, in Washington, DC, by Elizabeth Mittendorf, MD, assistant professor of surgical oncology at the University of Texas MD Anderson Cancer Center, in Houston.

"We don't yet know on a molecular level what causes tumors to change," Dr. Mittendorf said, but the change in status could explain resistance to trastuzumab therapy. She emphasized that more research is needed, but in the meantime it is important to keep this phenomenon in mind, "so that we can provide patients with the most appropriate targeted therapy for their cancer's biology."

"This highlights yet again the importance of obtaining tissue," commented Eric Winer, MD, director of the Breast Oncology Center at the Dana-Farber Cancer Institute, in Boston, Massachusetts. "There are still many questions about this finding," he said. "Were these tumors heterogenous to begin with? Maybe trastuzumab knocked out all the HER2-positive cells and left the HER2-negative ones behind? Or was it really a conversion of status?"

Whatever the mechanism involved, resistance to trastuzumab is a real problem, and "we need to figure out which drug to use next," Dr. Winer commented. He was moderating a presscast organized by the American Society for Clinical Oncology, a cosponsor of the meeting.

The new finding comes from a study of 143 patients with early-stage or locally advanced breast cancer, all of whom initially tested positive for HER2 status. After neoadjuvant chemotherapy (with a taxane and anthracycline) in addition to trastuzumab, all patients underwent surgery. Half the patients achieved a complete pathologic response, with no evidence of invasive disease in the breast or lymph nodes at the time of surgery.

Another 23 patients who did not have a complete pathologic response had pre- and posttreatment tissue samples available for analysis. Of these, 30.4% were found to have converted from HER2-positive to HER2-negtaive status by the time they had surgery.

Follow-up data (from a median of 10.2 months) suggest that these tumors are more aggressive, Dr. Mittendorf commented. Compared with patients who achieved a complete pathologic response, patients who did not were 3 times more likely to have their cancer recur (2.8% vs 11.3% of patients).

The finding suggests that any residual tumor found at the time of surgery should be reassessed for HER2 status, the researchers commented. There also needs to be some consideration given to what adjuvant therapy should be recommended this patient population.

The researchers have disclosed no relevant financial relationships.

2008 Breast Cancer Symposium: Abstract 150.