CR Reports From the San Antonio Breast Cancer Symposium (SABCS) 2010
CR Magazine: Collaberation – Results

Our Contributors

Dr. Susan Love
Kevin Begos
Musa Mayer

THE SYMPOSIUM

33rd ANNUAL CTRC-AACR SAN ANTONIO BREAST CANCER SYMPOSIUM

The 2010 CTRC-AACR San Antonio Breast Cancer Symposium is presented by Cancer Therapy & Research Center at UT Health Science Center San Antonio, the American Association for Cancer Research and Baylor College of Medicine.

SABCS @ AACR

Find SABCS information on the AACR website.

AACR VIDEO PODCASTS AND TELECONFERENCES FROM SABCS

Throughout the symposium, a series of press briefings and interviews with researchers and patient advocates will take place. Recordings will be posted as they become available, beginning late in the day on Thursday, Dec. 9.

ALAMO BREAST CANCER FOUNDATION PATIENT ADVOCATE PROGRAM

The AACR is teaming up with the Alamo Breast Cancer Foundation to present a new element to the Alamo’s advocacy program at the San Antonio Breast Cancer Symposium. Dr. Edith Perez and Dr. Andrea Richardson, renowned experts in breast cancer research, will be the special interest session guest speakers.

ENJOY CR'S PODCASTS?

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CR REPORTS FROM THE 2010 SABCS

Each year, the SABCS conference provides a forum for communication about clinical, translational and basic research among researchers, health professionals and those with a special interest in breast cancer.


From Dec. 8 to Dec. 13, 2010, look here for updates from CR about the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, in Texas. Please scroll down to view all reports and podcasts from the meeting.



MONDAY, DEC. 13, 2010

SABCS ROUND-UP: An overwhelming sense of urgency

Post by Musa Mayer

There was nothing small about the 33rd Annual San Antonio Breast Cancer Symposium. This year, there were 7,900 attendees over four days, during which basic scientists, as well as translational and clinical researchers, from 94 countries around the world, made some 2,000 podium and poster presentations. So maybe it’s not surprising that the first word that comes to mind to describe this largest annual scientific meeting dedicated solely to breast cancer research would be “overwhelming.” Although it’s my 15th year at this meeting, I have to admit that identifying the most important findings seemed particularly challenging. Other advocates were struggling with this, too.

New Possibilities
We are always looking for new and better treatments, of course, and several preliminary randomized trials did suggest some promising approaches. When combined with trastuzumab (Herceptin), a targeted agent called pertuzumab (Omnitarg) offered before surgery to women with HER2-positive early breast cancer [S3-2] shrank tumors completely in one out of five women. When docetaxel (Taxotere) was added, this “pathological complete response” (pCR) occurred in half of patients—although it’s still unknown whether pCR will translate to a long-term benefit that justifies a sure-to-be-costly combination. A small study in hormone-sensitive metastatic breast cancer patients whose cancer had already progressed on an aromatase inhibitor showed that combining tamoxifen with the mTOR inhibitor everolimus (Afinitor) reversed resistance, significantly improving response rates and time to disease progression [S1-6]. In another small study, hormone-sensitive metastatic breast cancer patients receiving high-dose (500 mg) fulvestrant (Faslodex) as their first-line hormonal treatment responded for nearly two years before their disease progressed, while on daily anastrozole (Arimidex) they experienced progression after only 13 months [S1-3]. The newly approved RANK ligand inhibitor denosumab (Xgeva) improved pain over zoledronic acid (Zometa) in women with bone metastases [P1-13-01]. Each of these studies awaits confirmation (or lack of confirmation) in larger, definitive phase III trials.

Instructive Failures
In some ways, this year’s Symposium could be described as a “negative” meeting. Defying the usual expectations, there were no blockbuster drugs, and few if any electrifying findings that the media could turn into hopeful news. Yet some of what I was hearing seemed a refreshing departure from the usual overblown, incremental tweaking of previously proven drug strategies.

Negative findings, in which a new drug or strategy is proven to be no better than the standard of care, often go unreported and unpublished—yet the contribution of such studies can be crucial. At this meeting, significant podium time was spent highlighting strategies that didn’t work, after being tested in randomized controlled trials. This introduced a strong note of caution about embracing new therapies prior to the discovery of good evidence to support them.

In one such study, the addition of the drug Xeloda (capecitabine), an effective single agent in metastatic breast cancer, to a standard adjuvant chemotherapy combination offered no benefit [S4-2]. When compared with each other, the aromatase inhibitors exemestane (Aromasin) and anastrozole (Arimidex) showed no difference in efficacy [S1-1]. Adding goserelin (Zoladex) to tamoxifen was shown not to improve outcomes in pre-menopausal patients [S1-5]. Despite being a recognized treatment for the condition, the use of manual lymphatic drainage was not able to actually prevent lymphedema [S5-3], although weight-lifting did seem to have a beneficial effect [ES9-3].

Most strikingly, the AZURE trial [S4-5] tested the impact of the intravenous bisphosphonate zolendronic acid (Zometa) to prevent or delay recurrence of primary breast cancer. Hopes had been high for a positive outcome, after an earlier study had shown promise in premenopausal women with ovarian suppression. Some oncologists had already begun to offer their patients adjuvant Zometa. However, in the larger study, Zometa had no effect on recurrence.

Biomarkers were a subject of much concern. Lack of concordance in HER2-, ER- and PgR-testing results among primary-tumor tissue samples and samples taken from metastases might lead to changes in treatment recommendations for many patients, one study showed [PF10-06]. Researchers had already established 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. While it had been widely hypothesized that this mutation would reduce the effectiveness of tamoxifen, tissue analyses from two large clinical trials failed to detect any clinical impact of the mutation [S1-7] [S1-8]. Said Clifford A. Hudis, the chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center: “This year’s theme was about being careful not to let your biases get ahead of the data.”

We Don’t Always Use What We Know
Another sobering theme of the conference involved evidence that people do not always adopt proven strategies, for reasons that remain unclear. A mini-symposium offered a welcome focus on disparities in cancer care and outcomes, particularly among underserved minority populations. New sources of data from health care payer records demonstrated broad issues related to compliance across all populations, including evidence suggesting that half or fewer of early breast cancer patients complete five years of recommended adjuvant treatment with aromatase inhibitors [PS-11-05]. While a U.S. study found co-payment a factor in compliance with hormonal treatment [S6-4], studies in Europe, where universal health care coverage is the norm, found similarly low rates of compliance, unaffected by educational materials designed to raise compliance [P5-1-05] [P1-10-03] [P5-11-06].

As if the media haven’t covered mammography screening enough, from my unofficial search, arguably the most common headline from the Symposium read: “Only half of women get annual mammograms.” This finding was based on a very large claims database [S4-7]. In keeping with this theme, a number of studies showed that modifiable factors, principally obesity, may have an impact on survival. Data from a number of cancer cooperative group trials as well as European studies strongly correlated high BMI (body mass index, a measure of height and weight) with poor outcomes in post-menopausal women, who are ironically the most likely to experience weight gain following treatment [S2-1] [S2-2]. Two of the poster discussions focused on this issue, as well as possible roles played by diabetes, insulin-resistance and the drug metformin. [PD03-01] [PD-03-06]

Shift to Translational Science
In recent years, the San Antonio Breast Cancer Symposium has changed dramatically. “Translational research permeates everything we do,” said Mitch Dowsett, a breast cancer researcher from the Royal Marsden Hospital in London, noting that at least 60 percent of the abstracts now connect basic science with patient care.

While much of the science is complex and difficult to comprehend, themes that repeat from conference to conference help me to identify the more promising areas of research and to follow them as they develop, be they breast cancer stem cell research, or the “synthetic lethality” of the new PARP inhibitors in triple-negative and BRCA-mutation carriers—to cite only two of several promising areas of inquiry.

Cancer used to be a biology problem, according to breast cancer specialist and ASCO President George W. Sledge Jr., who gave the prestigious William L. McGuire Memorial Lecture at SABCS on Saturday. Now, he said, “Cancer is a math problem.” Just 13 years ago, it cost $3 billion to sequence the human genome. Today, a $1,000 genome chip is almost a reality, making truly individualized treatment a tantalizing possibility. But the sheer number of data points argues against this. Most cancers have multiple gene mutations or defects, making multitargeted therapy necessary for optimal effectiveness. Yet the complexity of enrolling participants in clinical trials to study “smart” cancers, with multiple gene mutations, will be mind-boggling. Triple-negative breast cancers may have more than 7,000 genes differentiating them from normal breast tissue, something Sledge referred to as “genomic chaos.” Today, the clinical trials and regulatory systems are still focused on studying single agents with single targets. “The current system,” Sledge stated flatly, “is not designed to handle chaos.” The next generation of cancer clinical trials will have to be multitargeted and based on personal genomics, with real-time bioinformatics and a wholly different regulatory system. Alternatively, trials will have to focus outside the world of targeting kinases, on DNA-repair mechanisms or metastasis-suppressor genes, or on immune- or microenvironment-based approaches. Clearly, the science itself is demanding a fundamental change in how research is conducted.

Leaving the convention center on the last day of the Symposium, I felt cautiously hopeful. Advocates working on the 2020 Breast Cancer Deadline campaign are determined to make a real contribution to focus and forward the breast cancer research agenda. We feel a sense of urgency. Of course, no one can know where and when the next big breakthroughs will come, but when they do, we can be sure of one thing: It won’t be soon enough. Not for the half million women (and men) around the world who will die this year of breast cancer, many of whom will never have had a chance to reap the fruits of the research so elegantly on view this year, as every year, at the San Antonio Breast Cancer Symposium.

 


 

FRIDAY, DEC. 10, 2010

San Antonio: Blog #2

Post by Dr. Susan Love

I was really disturbed when I heard the news this morning. There were two big Symposium-related stories. One of these stories was based on a poster that will not be presented until Saturday that addresses the use of estrogen alone to treat menopausal symptoms. The other, which will not be presented until later today (Friday afternoon), is on zoledronic acid (brand name zometa) and breast cancer recurrence. This means that what was in the paper and on the news on Friday morning was based on press reports put out by the authors and on data that participants at the meeting had not yet been able to evaluate.

My comments, therefore, are on the estrogen alone study press release and abstract. Basically, this study is a reanalysis of the estrogen-alone arm of the Women’s Health Initiative. This arm has already been reported as showing an increase in breast cancer. In addition, other studies have shown that it may take longer to see the effect from estrogen only than it does from a combination of estrogen and progesterone.

As you read the media reports, it is important to remember that the estrogen-only arm of the study enrolled only women who had undergone a hysterectomy (removal of the uterus). These are the only women who can take estrogen alone, as doing so can increase the risk of uterine cancer.  What we don’t know is how many women in the estrogen-only arm of the study also had had their ovaries removed. This is important information to have because removing the ovaries reduces a woman’s risk of breast cancer by about 70%.  

Also, the data reported in the abstract suggested that the only risk reduction was short-term and that it was only in women who did not have a family history of breast cancer or had had a previous breast biopsy. I would be very interested in whether breast density seen on mammogram was also related to breast cancer risk. Unfortunately, I won’t be able to tell you until Saturday, when we get to see all the data. (As you can probably tell, I do not think this poster should have been singled out to be promoted to the media and, if it was going to be promoted, it certainly shouldn’t have been done until after conference participants had had a chance to see the data!) 

This morning (Friday) the first several presentations were on HER2-positive breast cancer. These studies evaluated the effectiveness of giving trastuzumab (brand name Herceptin) and two new drugs that also target HER2-positive tumors lapatinib (brand name Tykerb) and pertuzumab with and without chemotherapy prior to surgery to women with large tumors. Giving drugs before surgery (called neoadjuvant treatment) is being done more and more in clinical trials because it allows the researchers to see whether the tumor is responding to the drug. (If the tumor is responding it will get smaller.) 

Two of the studies compared Herceptin to Tykerb, and the researchers reported that in both studies Herceptin was more effective. The combination of Herceptin, Tykerb and chemotherapy had a 50% complete response rate (this means that 50% of the time no cancer was seen at the time of surgery), with women who were estrogen receptor (ER) negative more likely to have a complete response. However, as Dr. Eric Winer, the director of the breast oncology center at the Dana-Farber Cancer Institute in Boston who led the session discussion pointed out, overall, women with ER-positive tumors do better, so whether there is a complete response is only one factor in overall survival.

The next presentations focused on other drugs now in the pipeline for treating HER2-positive tumors. For those of you who have triple-negative tumors, that session is coming! Alan Ashworth, a professor of molecular biology at the Institute of Cancer Research, in London, received an award and gave a good talk on the concept behind the PARP2 inhibitors and some new approaches to finding new drugs.  

A surgery session reviewed local treatment and the only new piece of information was that the current trend seems to be either breast conservation or bilateral mastectomy. The problem with a risk-reduction mastectomy, though, is that the risk of recurrence from the first cancer is usually higher than the women’s risk of getting a second cancer in the other breast. Lastly, several papers were presented that updated data on chemotherapy studies. We learned, for example, that TAC (Taxol or Taxotere, Adriamycin, and Cytoxan) seems to be better than FAC (fluorouracil (5FU), Adriamycin, and Cytoxan).

The other study that had been widely reported this morning was on Zometa, a bispohosphonate similar to alendronate (brand name Fosamax) but given IV. Unlike the estrogen-only study, though, this one is very interesting and important.

Initial observational studies (non-randomized studies that compare a group who are taking a drug for whatever reason to a group who are not taking it) had suggested that women with breast cancer who took Zometa had less bone metastases and higher disease free survival. Also, earlier data from an Austrian study had shown that Zometa not only helped prevent bone loss from treatment but also seemed to decrease recurrence in the breast and the bones.

Today, researchers reported data from a much larger European trial, called AZURE, that randomized women with Stage II or III breast cancer to either have standard therapy or standard therapy with Zometa. The study found that there was no improvement in disease-free survival or bone metastasis survival. In addition, there were 17 episodes (1.5%) of osteonecrosis of the jaw in the women who received Zometa. These findings were very disappointing and everyone was trying to figure out why this study was so different from the first one. Much more discussion will take place, but for now we should probably reevaluate giving women Zometa to decrease recurrence.

Lastly, an interesting study was added in at the end of this session. This study (which has also gotten a lot of media attention) looked at how many women in the United States actually got mammograms between 2006 and 2009. The researchers used only fully insured women in the study so that the data would not be influenced by ability to pay. Interestingly, they found that only 57% of women age 40-50 and 65% of women 50-64 were getting annual mammograms. We know women are greatly concerned about breast cancer, and this study show that there are large groups of women who have insurance who could be getting mammograms who aren’t. Now, we need to learn why.

 


 

FRIDAY, DEC. 10, 2010

 PODCAST: SABCS Highlights With Dr. Love

Post by Kevin Begos

Susan M. Love, MD, the founder of the Dr. Susan Love Research Foundation, discusses highlights from the symposium.

Listen here (3.7 MB / 5:26  minutes)
or
Subscribe to CR podcasts via iTunes

All CR podcasts are FREE!


 

THURSDAY, DEC. 9, 2010

San Antonio Blog: Day 1

Post by Dr. Susan Love

The San Antonio Breast Cancer Symposium is the most important breast cancer meeting that takes place each year. It attracts close to 9,000 participants from more than 90 countries who are interested in hearing and discussing the most recent breast cancer research findings. The 33rd annual Symposium is being held December 8-12, 2010, and Dr. Love will be posting daily blogs about the meeting’s most interesting research reports and discussions.

Hormone Therapies
The first session of this year’s Symposium focused on hormonal drugs. Researchers reported findings from studies that showed that exemestane (brand name Aromasin) and anastrozole (brand name Arimidex) are about the same, with slightly less side effects for exemestane; that goserelin (brand name Zoladex) has the same benefit as tamoxifen when given to ER-positive premenopausal women for two years; that there was no benefit from taking goserelin and tamoxifen together; and that the benefit from goserelin, but not tamoxifen, was greater in tumors that were strongly estrogen receptor (ER) positive.

The next presentation, which reviewed two studies looking at the CYP2D6 test and the benefits of tamoxifen, were more interesting. The CYP2D6 test, also called the "tamoxifen resistance" test examines a gene called 2D6, which produces the enzyme CYP2D6. This enzyme is necessary for the body to metabolize a number of drugs, including tamoxifen. Tamoxifen has to be metabolized to endoxifen in order to work. This is done in the body by enzymes. Some people have variations in these genes that result in them making less endoxifen, and there has been some data suggesting that these people don’t do as well when they take tamoxifen. This was noted at the 2007 San Antonio Breast Cancer Symposium, when researchers presented data that showed that women who inherited a certain variation of the 2D6 gene were almost twice as likely to have their breast cancer recur, even though they were more likely to complete their tamoxifen treatment.

To explore this question further, researchers took advantage of two large studies that were done to look at the benefit of tamoxifen versus an aromatase inhibitor (which is metabolized differently, and is not affected by CYP2D6). Their findings refuted the previous data, showing that the presence of common mutations in the genes that control the enzymes that metabolize tamoxifen did not have an effect on whether women were likely to have a recurrence. They also found that antidepressants that are thought to inhibit CYP2D6 actually had no effect on whether women taking tamoxifen had a recurrence. In sum, the researchers concluded that for postmenopausal patients with hormone-sensitive early breast cancer, CYP2D6 testing is not justified to determine whether to give tamoxifen. They also found that, in contrast to what has been suggested, the presence or absence of hot flashes should not be used as an indicator of whether tamoxifen is effective.

Basic Science
This meeting is a combination of basic science and clinical science. I always love the basic science sessions because I learn a lot. One of today’s sessions focused on how cells metastasize, and what happens next. The data shows that this is actually a very inefficient process, with  only 2% of the metastatic cells actually arriving at a new organ and with about one-third of these cells remaining completely dormant in the new organ for as long as 20 years or more. Interestingly, in the researchers’ models, chemotherapy had no effect when the cells were dormant, but it did have an effect once the cells woke up.

Dormant means asleep, and the second speaker talked about how that dormancy works. This research team looked to see whether dormancy was related to blood supply (it wasn’t) or the balance between cell death and growth. They found that the cells were basically just not dividing when they were dormant. They then went on to see if there were molecular differences between the cells that woke up and those that did not, hoping that they could then go on to develop new drugs that target and stop the molecules that only are in the cells that wake up. While that would be great, it made me think that we should also be looking at the environment that keeps the cells asleep. After all, the goal is not to kill dormant cells but to live your life and die a natural death with the cells still dormant.  

Obesity & Breast Cancer Survival
The talks that followed may have given us a clue to one factor in the cell’s environment that stimulates metastasis. Researchers reported findings from three studies that analyzed the effect that being overweight or obese has on a woman’s risk of having a recurrence or dying of their disease.

The first set of studies looked at women with ER-positive, HER2-positive, or triple negative breast cancer. These studies found a significantly higher risk of death from breast cancer in women who had a body mass index (BMI) over 25 (these are women considered overweight) who were ER positive. In fact, in premenopausal ER-positive women there was a 51% increased chance in death in the women who were obese! This higher risk of death was not seen in women with a BMI over 25 who had HER2-positive or triple negative tumors.

A second study looked at women with locally advanced node positive (3 or more positive nodes) breast cancer. This study also showed a worse prognosis in women who were obese. It was mentioned that the goal is not to become skinny, and it was reported that the Women’s Intervention Nutrition Study (WINS) showed that losing just 6 pounds made a difference in survival. The last study looked to see if it mattered whether women who were overweight were on an aromatase inhibitor or on tamoxifen. The researchers reported that it didn’t matter which therapy they were on, as the risk of death was the same for both treatments.

I couldn’t help but think that if we had a drug that had that much effect as obesity on women’s risk of dying of breast cancer we would be writing headlines! At this point I believe there is enough data to suggest that obese women should routinely be entered into a weight loss and exercise program as part of their treatment.

More tomorrow…

 


 

THURSDAY, DEC. 9, 2010

 PODCAST: Pathobiology of Breast Cancer

Post by Kevin Begos

Andrea L. Richardson, MD, PhD, of Brigham and Women's Hospital in Boston, discusses the biology of breast cancer and the history of the understanding and treatment of the disease.

Listen here (4.1 MB / 5:35 minutes)
or
Subscribe to CR podcasts via iTunes

All CR podcasts are FREE!


 

THURSDAY, DEC. 9, 2010

 PODCAST: Novel Strategies for Breast Cancer Therapy

Post by Kevin Begos

Edith A. Perez, MD, of the Mayo Clinic in Jacksonville, Fla., discusses progress toward improved classification of breast cancer subtypes and how biomarkers are related to the treatment of the disease.

Listen here (3.5 MB / 5:03 minutes)
or
Subscribe to CR podcasts via iTunes

All CR podcasts are FREE!


   

FRIDAY, DEC. 10, 2010

 PODCAST: SABCS Highlights With Dr. Love

Post by Kevin Begos

Susan M. Love, MD, founder of the Dr. Susan Love Research Foundation discusses highlights from the symposium.

Listen here ( 3.8 MB / 5:26 minutes)
or
Subscribe to CR podcasts via iTunes

All CR podcasts are FREE!