[RobinP]

You may recall that once the adjuvant Herceptin trials reported such huge increases in DFS, just last year at the 2005 ASCO and 2005 SABC, many older diagnosed her2+s that didn't get Herceptin in their adjuvant treatment started it late, sometimes years later.I think many of those individuals were left with a challenging choice, whether to do delayed Herceptin or not, since the benefits of Herceptin were not given for late initiation. Suddenly we now learn that there is an arm of late users in the HERA trial that is being evaluated with seemly positive preliminary results.

I am not surprised with the results being positive. However, I do think there will be less and less positive returns for Herceptin as time to start delayed treatment increases. What exactly is the time limit is the question. However, one would expect that those most likely to relapse, with more positive nodes, would continue to have high residual risk for a longer period of time from initial diagnosis. And these patients would probably benefit the most with Herceptin given late compared to patients with low risk for relapse.

Also, we know that most her2+ events occur the first few years after diagnosis, with a peak of relapse about 18-24 months after diagnosis. I would assume that those starting late adjuvant during or prior to this peak of relapse MAY obtain a particular advantage over those starting after this peak with delayed Herceptin.

More and more we are learning that potential risk for cardiac toxicity with adjuvant Herceptin is low, particularly if trastuzumab is given sequentially, after anthracyclines. I would expect the trend of low cardiac toxicity to follow with late Herceptin as well. So I don’t see cardiac issue being a major problem with late Herceptin, at least in the short run. Of course, no one knows the long term toxicity of Herceptin which may be even more of a consideration with late delayed Herceptin.

As always true, every update and advance in the clinical trials, only provides us with more questions to replace those already answered. It would be nice if we had the answers to all of our questions more quickly so that everyone would make the best choices possible for optimal treatments. However, particularly in the case of the use of late Herceptin, not much direction was offered from the ASCO and SABC conferences last year, when at the same time so much information was given to those newly diagnosed. I commend all patients and physicians who had to make difficult decisions regarding late Herceptin when the major cancer societies gave no direction.