Saturday, December 16, 2006

Barbara Brenner, Former Executive Director

Risk Reduction, Prevention, and Misplaced Priorities

This is my last day at this conference, and what I was most looking forward to—in a “let me at ‘em” sort of way—was the afternoon mini-symposium on “Recent Advances in Breast Cancer Prevention.” Jane Zones has written her analysis of the central presentation at that session—the talk by Leslie Ford. What I was hoping to ask Dr. Ford had to do with the next “prevention” trial that will start recruiting next spring. It’s being called “STELLAR,” and it will compare raloxifene (which, despite the evidence to the contrary, the NCI continues to characterize as the “winner” of the STAR trial comparing raloxifene to tamoxifen) to Femara (letrozole), an aromatase inhibitor (AI).

Given the preliminary results of BCA’s AI survey, presented as a poster at this meeting last night, other abstracts presented here showing that women are discontinuing use of AIs for treatment at very high rates, and comments from drug company reps to me that describe compliance with AI regimens in the adjuvant treatment setting as “dismal,” I wonder what the promoters of this new trial can be thinking. If women who ostensibly need these drugs for treatment won’t take them, why would healthy women do so? The side effect profile is simply not pretty.

There were a couple of other presentations in the “prevention” session. These focused on looking for biomarkers that might help identify effective risk reduction agents in a shorter time frame, and looking for new agents that will reduce the risk of estrogen negative disease. (All of the currently available pills reduce the risk of ER+ disease, not ER negative disease.) Cox2 inhibitors (Vioxx was one of these) are under investigation in this context. (These occur naturally in resveratrol and green tea). The surprising thing mentioned during these presentations was that at least one center is looking at combining an AI with hormone replacement therapy as a risk reduction strategy.

I struggle not to get caught up in the prevention culture of this meeting. After all, the most we can say about the pills that have been studied so far—tamoxifen and raloxifene—is that they reduce the risk of breast cancer, since someone women on the drugs developed breast cancer in the trials. So risk reduction is the best we can say about these therapies. And the likelihood that we’ll ever be able to prevent breast cancer without increasing the risk of some other disease seems so remote to me that I’m really not interested in hearing much more about it. Even when the focus is on finding new targets at the cellular level, I am concerned that interfering with one part of the cellular structure will lead to downstream consequences that we can’t imagine, let alone envision. Why can’t we put all these resources into figuring out what’s triggering our cells to go haywire? A message for another meeting, I guess.

Micrometastases and Beyond

About 10 years ago, thanks to demands from women who were tired of suffering the consequences of axillary node dissection (ALND), surgeons developed the technique of sentinel node biopsy (SNB). Today we heard a number of presentations about the micrometastases that are found with this technique, and their implications for disease prognosis.

While there was a lot of talk about techniques to be used in reviewing tissues, the take home messages from the patient’s perspective were pretty simple, and were given in the plenary talk by Emiel Rutgers:

  1. SNB is here to stay. The false negative rate (finding no cancer when cancer is actually present in the sentinel node) is less than .5%
  2. If micrometastases are found on SNB, an ALND should be done.
  3. Micrometastases that are less than .2 cm. in size have no clinical relevance, and nodes with micrometastases this small should be considered negative.