San Antonio Breast Cancer Symposium 2008—An Overview

By Jane Zones and Barbara A. Brenner

Alamo

BCA staffers Barbara Brenner and Allison Young, and board member Jane Zones, attended the San Antonio Breast Cancer Symposium (SABCS) in December 2008. More than 8,000 physicians and researchers attended the conference this year, along with droves of drug and device manufacturers and a small number of breast cancer advocates.

The symposium consisted of four days of ten- to 30-minute presentations, six sessions where numerous “posters” (smaller-scale discussions) were presented, special sponsored sessions in the evenings, and a variety of other events. The scientific presentations took place for the most part in a vast auditorium that held thousands of participants. Speakers and their slides were projected on huge screens that hung throughout the hall. No more than five minutes for questions were provided for any presentation.

This article highlights some of the themes of the conference. You can visit our web site to retrieve more detailed descriptions of the various events we attended. And abstracts and slides from most of the presentations are online at www.sabcs.org. You can log on as a guest for complete access.

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Metastasis—Finally on the Radar Screen

As most people dealing with breast cancer know, once the disease has metastasized (spread from the breast to life-sustaining organs or to bone), it cannot be cured. We desperately need to figure out how to prevent metastasis from occurring and how to treat it more effectively when it does occur.

Metastasis got a lot more attention at SABCS this year, and that’s a good thing. There were four major overview presentations on metastasis: oncirculating cancer cells (Klaus Pantel), tumor “self-seeding” (Larry Norton), metastasis suppressor genes (Patricia Steeg), and the unique aspects of breast cancer metastasis as distinguished from lung and colon cancer metastasis (Joan Massagué). Massagué is coauthor of a special article on this topic in the December 25, 2008, issue of the New England Journal of Medicine.

This is important work, especially in the ongoing effort to individualize care, treat only those who would benefit from particular treatments, and more effectively treat metastatic disease. You can find more details about these presentations on BCA’s web site.

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Overcoming Drug Resistance: How to Make Drugs Keep Working

Some women treated with tamoxifen develop recurrences, or metastases, indicating that the drug has stopped working. Indeed, development of resistance in some patients is found with all cancer drugs. Several of the sessions at SABCS dealt with overcoming Herceptin resistance

“Will the result be yet more treatment—and more expense and more unnecessary side effects as we grasp for anything that might keep patients alive?”

“Signal transduction inhibitors” (STIs) are drugs like Herceptin (trastuzumab) that inhibit signals between cells that are involved in the cancer promotion process. Stephen Johnson presented a theory that resistance to tamoxifen can be overcome or prevented by giving an additional STI drug.

Johnson made it clear that his theory is just that, and that it is not yet ready for clinical application. Among other things, performing biopsies will be necessary to understand what cell pathways are active in a given patient so that the correct STI can be chosen to inhibit that pathway. While Johnson was clear that understanding of this process is still being developed, we feared that some of the clinicians in attendance would come away thinking that combining an STI with a hormonal therapy will overcome resistance.

It’s still uncertain who is likely to develop resistance. Will the doctors who read about this presentation decide to give both drugs to everyone so that they’ll reduce the risk in the ones who will benefit? Will the result be yet more treatment—and more expense and more unnecessary side effects as we grasp for anything that might keep patients alive.

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Sequencing Hormonal Treatments

A number of presentations addressed combining hormonal treatments with other drugs and the sequencing of drug treatments to maximize benefit

Not long after aromatase inhibitors (AIs) came on the scene for adjuvant treatment of breast cancer to reduce risk of recurrence, the medical community began to ask whether patients already on tamoxifen would do better by being switched to an AI. And trials have been reported at previous SABCS meetings looking at the benefits of switching.

We heard five different presentations that considered which hormonal drugs to prescribe, in what order, and whether the order mattered: Abstracts 11(lasofoxifene [SERM] to reduce risk of breast cancer, 12 (meta-analysis of switching studies of tamoxifen and AIs), 13 (letrozole and tamoxifen, alone and sequenced), 14 (tamoxifen alone vs. tamoxifen switched to anastrozole), and 15 (tamoxifen vs. tamoxifen switched to exemestane). A more complete description of these abstracts can also be found on BCA’s web site.

“…the drumbeat for AIs continues to build…”

So, what’s the take-home for all of these studies? It seems to be that the drumbeat for AIs continues to build, though which one to give, whether to give tamoxifen first, and how long to continue treatment remain unanswered questions. We have more information, but not more knowledge.

There are several other things to note about these studies:

  1. Many of them found statistically significant differences. Keep in mind that “statistically significant” does not mean “large” or “meaningful.” What it means is that the phenomenon is very likely real, not a chance outcome.
  2. Several of these studies involved unblinding of the trials and crossover, meaning that women in the “control” arm of the study could then get the “treatment” being offered in the study. Crossover seriously complicates the analysis of results and very likely biases the results in favor of AIs. While the reason for allowing crossover is compelling—if something seems to work, shouldn’t everyone have the chance to get it?—the practice undermines the results of the trials. Wouldn’t women be willing to forego unblinding and crossover if they understood the need to have more reliable trial results? Shouldn’t we ask them?
  3. Most of these trials were funded by the companies whose drugs were being tested.

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Imaging

There were a number of talks on breast cancer imaging, both for detection (screening) and for making a more precise diagnosis after a tumor is detected.

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Ultrasound in Breast Cancer Screening

Wendie Berg, a radiologist, started from the premise that mammography is the gold standard but noted that some subgroups of women may not benefit from mammography. She thinks that women at high risk of developing breast cancer should get MRIs for screening under the American Cancer Society’s guidelines. And she also maintains that women getting MRIs and mammograms don’t need to do ultrasound, too.

But for women at intermediate risk, Berg finds lots of things to favor ultrasound: it’s relatively inexpensive, widely available, not radiation based, and well tolerated. The ongoing trial of ultrasound for screening—ACCRIN 666—which published its first results in JAMA in May 2008, shows that ultrasound is good at finding small lesions and node-negative disease, but there are a lot of false positives, leading to unnecessary biopsies. Of course, this happens with every detection method currently in use.

Issues of technologist training and insurance reimbursement also need to be resolved. And, as is always the case whenever the discussion is about screening, Berg pointed out that ultrasound supplements but doesn’t replace mammography.

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MRI as a Diagnostic Tool

Monica Morrow is a surgical oncologist who heads Memorial Sloan-Kettering Cancer Center’s Breast Service. Her major research interest is the application of knowledge from clinical trials to daily surgical practice, and her talk was a beautiful example of this.

MRI is used in detecting breast cancer in asymptomatic women (screening) and in providing information to improve patient outcome in women with breast cancer (diagnosis). Morrow addressed MRI’s use as a diagnostic tool only. The potential benefits of MRI in diagnosis are to refine decisions about breast conservation therapy, determine the extent of the tumor, identify potential contralateral cancer, and decrease the risk of local recurrence.

In a range of studies, the total number of mastectomies is persistently double in women who have MRI. Furthermore, having MRI delays surgery for an average of three weeks. Diagnosis-related MRI studies have been retrospective and not randomized. Women who undergo MRI are on average six years younger and are selected for imaging because they are more likely to benefit, which would result in more favorable research outcomes for MRI. Even so, no advantage has been shown for such imaging.

Morrow summed up by saying that MRI finds more cancer but what is found is not clinically relevant. Neither short-term surgical outcomes nor long-term local control or contralateral cancer rates are improved with MRI. Because of this, she recommends MRI only for BRCA1 and 2 carriers, those who present with positive lymph nodes, those who are being assessed for neoadjuvant therapy, or those whose diagnosis is not resolved by physical exam, mammogram, and ultrasound.

“The routine use of MRI in cancer patients requires some evidence of clinical benefit. To date, this [evidence] does not exist.”

“The routine use of MRI in cancer patients requires some evidence of clinical benefit,” Morrow said, as she ended her lecture. “To date, this does not exist.”

Morrow’s presentation was followed by a report on the first and only prospective study of MRI, the COMICE trial, which was sponsored by the research arm of the British National Health Service. (England and Canada sponsor significant research on actual effectiveness as a means of cost containment). The results of COMICE substantiated Morrow’s perspective

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In Summary

Attending SABCS, for those of us who are not medical researchers, was a major challenge, but it is important for those of us who follow the progression from ideas to treatment. Our web site includes daily accounts of events we attended, but everyone has access to slides and abstracts on the SABCS web site. We encourage you to make use of this information.

Jane Zones is a medical sociologist and a board member of Breast Cancer Action.

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