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You should remember more than the Alamo
By Dianne Armitage
The San Antonio Breast Cancer Symposium (SABCS) is the largest annual scientific meeting focusing on breast cancer, which means what happens in San Antonio should not stay in San Antonio. Women need to find out what is being explored, discovered, dismissed and discussed in order to make more informed decisions about breast care.
December 2010 marked the 33rd year that scientists, researchers, doctors and advocates have come together to share findings and frustrations in this venue. Over 7,500 people were in attendance. With more than 2,000 podium and poster presentations taking place over the four-day symposium, the stream of information is overwhelming to say the least, so it’s not always easy to determine what findings present the most meaningful take-home messages.
2010’s Symposium wasn’t chock-full of hot new drug introductions or groundbreaking findings that the media could spin into hopeful headlines, but as longtime advocate and health writer Musa Mayer shares, “Some of what I was hearing seemed a refreshing departure from the usual overblown, incremental tweaking of previously proven drug strategies.”
It is her opinion that even negative findings, in which a new drug or strategy is proven to be no better than the standard of care, can contribute to our overall knowledge base so researchers know which directions do and don’t hold promise. These sorts of findings provide further caution about embracing new therapies prior to the discovery of good/sound supporting evidence. The following provide a few examples of how this played out.
Promising… but alas, no proof
One study indicates that the addition of the drug Xeloda (capecitabine), proven as an effective single agent in metastatic breast cancer, offers no benefit when added to a standard adjuvant chemotherapy combination.
When compared with each other, the aromatase inhibitors Aromasin (exemestane) and Arimidex (anastrozole) showed no difference in effectiveness.
Pre-menopausal women derive no benefit by adding Zoladex (goserelin) to Tamoxifen.
Although it has become a recognized treatment for the condition, the use of manual lymphatic drainage does not prevent lymphedema. Surprisingly, weight-lifting did seem to provide benefits, which will certainly warrant more study.
One of the biggest disappointments involves the AZURE trial which tested the effect of intravenous Zometa (zoledronic acid) in preventing or delaying recurrence of primary breast cancer. The scientific, medical and patient communities’ hopes had been high for a positive outcome, since an earlier study had shown promise in pre-menopausal women with ovarian suppression. The promise seemed so great, some oncologists had already begun offering their patients adjuvant Zometa. Unfortunately, in this larger study, Zometa had no effect on recurrence.
In the area of biomarkers, researchers already recognized that the presence of a mutated form of the enzyme CYP2D6 interferes with the creation of endoxifen, thought to be the active metabolite of Tamoxifen. (The hypothesis being that this mutation would reduce the effectiveness of Tamoxifen.) However, tissue analyses from two large clinical trials failed to detect any clinical impact of this mutation. Another subtle reminder that it’s important not to let perception get ahead of scientific evidence.
What we know isn’t always what we do
A somewhat puzzling thread occurring throughout the conference surrounded evidence that even when strategies have been shown to be effective, they are not always used. Although the reasons are uncertain, there was much discussion on why this might be occurring.
One mini-symposium focused on disparities in cancer care and outcomes, particularly among underserved minority populations. With new sources of data from health care payer records added to the mix, broad issues involving all populations and their compliance were discovered. These findings suggest that half or fewer of early breast cancer patients complete the recommended five years of adjuvant treatment with aromatase inhibitors.
Another study conducted here in the U.S. discovered that co-payment is a factor in compliance with hormonal treatment. Studies conducted in Europe, where universal health care coverage is the norm, found similarly low rates of compliance, unaffected by educational materials designed to raise compliance.
One hot topic in this area, and the source of much discussion, was the conclusion that only half of women get annual mammograms. This finding was based on a very large claims database. But that’s not the only startling societal discovery unearthed.
A number of studies indicate that modifiable factors like obesity may have an impact on survival, since data from several cancer cooperative group trials, as well as European studies, strongly correlated high BMI (body mass index, a ratio of height and weight) with poor outcomes in post-menopausal women. The irony here is that this same population is the most likely to experience weight gain following treatment.
The possible role played by diabetes, insulin-resistance and the drug Metformin was also discussed.
Just a few worth noting
There isn’t time or space to provide an overview of all of the topics covered – and since interests and needs vary so dramatically it’s not possible to highlight topics that speak to each person. However, the following should address some of the more common issues:
Data from an ongoing multi-center study suggests that the presence of even one circulating tumor cell (CTC) after surgery almost doubled the risk of recurrence in women with early breast cancer. Detection of five or more tumor cells after surgery tripled the survival hazard compared with patients who had fewer or no circulating cells. CTCs also predicted worse disease-free survival and distant disease-free survival.
A novel agent that inhibits DNA repair in cancer cells appears to be promising for safety and efficacy given along with chemotherapy using Camptosar (irinotecan), according to reported early-phase clinical trial results. What makes this particularly interesting is that the majority of the women (22 of the 34) had triple-negative disease marked by negative HER2 and estrogen and progesterone receptor status. Since women relegated to triple-negative status are always hungry for breakthroughs, this is noteworthy.
Women whose breast cancers were discovered during pregnancy don’t need to delay treatment, according to a German registry study showing that chemotherapy had no major effects on fetal outcomes. The study of 260 patients found that babies born to women who started chemotherapy during pregnancy were not significantly more likely to have reduced birth weights or adverse events, such as birth defects or neutropenia (a condition in which the number of a type of white blood cell is decreased), when compared with those not exposed during gestation.
If early-stage breast cancer patients can achieve a pathologically complete response before undergoing surgery it strongly correlates with improved disease-free survival – and better overall survival at the three year mark.
Preliminary results of a neo-adjuvant breast cancer therapy trial for HER2-positive tumors indicates that a four-drug combination has a high pathological complete response rate (pCR). When combined with Herceptin (trastuzumab), a targeted agent called Omnitarg (pertuzumab) offered before surgery to women with HER2-positive early breast cancer shrank tumors completely in one out of five women. When Taxotere (Docetaxel) was added, this pCR occurred in half of patients. What is still unknown is whether this will translate to a long-term benefit justifying what is sure to be a costly combination.
Researchers reported that the injectable anti-bone metastasis drug Xgeva (denosumab) delays skeletal complications of breast cancer five months longer than Zometa (zoledronate), an intravenous bisphosphonate considered the standard of care.
Several studies showed that aromatase inhibitors appear to increase the risk of cardiac events among women being treated for breast cancer. The relative risk of suffering a cardiovascular event increased 26%. It should be noted that this excess risk can be lowered if a woman is treated with Tamoxifen first and then switches to an aromatase inhibitor.
Research suggests women should get a second opinion when breast cancer test results come back HER2 negative. A study of almost 400 tumor block tests at three central laboratories to determine HER2 over expression conducted by expert pathologists found that the results were wrong in 8% of cases overall after the tests were reassessed by the pathologists’ peers. And in up to 10% of patients, the same tumor tested HER2 positive at one location but normal for HER2 at another.
Advocating for what’s next
Where is all of this headed? And what should we be demanding when it comes to research? While lecturing at the symposium, breast cancer specialist and ASCO (American Society of Clinical Oncology) President George W. Sledge, Jr. discussed how the dynamics are changing. “Cancer used to be a biology problem. Now cancer is a math problem.”
Only 13 years ago, the cost to sequence the human genome was $3 billion. In today’s world a $1,000 genome chip is nearly a reality, which in turn means that individualized treatment just may be enticingly close. What is the obstacle? Most cancers have multiple gene mutations or defects, making multi-targeted therapy necessary for optimal effectiveness.
Enrolling participants in clinical trials to study cancers with multiple gene mutations is excruciatingly difficult! (Just one example: triple-negative breast cancers may have more than 7,000 genes differentiating them from normal breast tissue.) Sledge referred to this dilemma as genomic chaos. “The current system,” Sledge stated flatly, “is not designed to handle chaos.”
Musa Mayer succinctly adds a bit of clarity to the chaos when she points out, “Today, the clinical trials and regulatory systems are still focused on studying single agents with single targets. This has to change for real progress to be made. What this means is that the next generation of cancer clinical trials must be multi-targeted and based on personal genomics. It will be crucial that trials focus outside the realm of targeting kinases, DNA repair mechanisms, metastasis-suppressor genes, or on immune and/or microenvironment-based approaches. Clearly, the science itself is demanding a fundamental change in how research is conducted.”
It is now time for the population all of this research is designed to serve to demand meaningful changes as well. An appropriate battle cry just might be – remember the San Antonio Breast Cancer Symposium!