This study is novel for several reasons. It is the first trial evaluating neoadjuvant trastuzumab, and there is a lot of interest in defining the response rate. Also, we performed cardiac analyses during the trastuzumab/paclitaxel therapy and again during the postsurgical adjuvant AC chemotherapy. Our results are very similar to George Sledge’s — a significant number of women had a 10-20 percent decline in their ejection fraction. Fortunately, none of the patients developed any symptoms of congestive heart failure, and the changes in ejection fraction appeared to reverse with time.
The decline in ejection fraction occurred either during or at the end of adjuvant AC and did not change much during the trastuzumab/paclitaxel therapy. Most of us believe these kinds of changes in ejection fraction are consistent with what occurs with AC alone, but since this is not a randomized trial, we do not know if the addition of trastuzumab influences the ejection fraction.
Harold J Burstein, MD, PhD
We published the results from a preoperative trastuzumab trial in 40 patients with Stage II or III breast cancer that had HER2 overexpression (IHC 2+ or 3+). A small number of patients didn’t have surgery and some had a pathologic complete response, so obviously in those situations we couldn’t reassess the tumor.
Of the patients with residual tumor, a small number of them had a change in their IHC status. The numbers get extraordinarily small, but it looks like the change in IHC status might be more common in patients with 2+ tumors initially, rather than 3+ tumors. The change in HER2 status typically went from 2+ or 3+ to 0 or 1+.
I don’t think we can say exactly what is happening. Perhaps it is just variability in testing, or it may be an effect of trastuzumab. Since we don’t have the FISH status on these patients yet, one possibility may be that those patients with a change in HER2 status may really have had FISH-negative tumors. We have a patient in our current study who has HER2-negative and HER2-positive tumor cells adjacent to each other, as assessed both by IHC and FISH.
Eric P Winer, MD |
