Sentinel nodes: A convergence of knowledge from different trials


One of the most important incremental steps in breast cancer has been to lessen the amount of axillary surgery that is needed to stage breast cancer. Sentinel node biopsy appears to lead a much lower risk of lymphedema compared to a standard axillary node dissection. (Axillary node dissection is the removal of some of the lymph nodes in the underarm area to determine the extent to which the cancer has moved outside the breast. This information helps determine staging of the cancer and could impact treatment choices. A sentinel lymph node biopsy only removes the closest one or few nodes to which cancer are likely to spread from the primary tumor.)

However, sentinel node biopsy was a genie that got out of the bottle too early and was widely adopted before it was formally proven to be as effective and accurate as axillary dissection.

Nevertheless, credit is due to several cooperative trial groups that conducted important randomized studies informing us of several points. Those findings were announced at this year's annual meeting of the American Society of Clinical Oncology.

First of all, there was a general confirmation that not only was a negative sentinel node status indicative of no further positive nodes remaining, but that omitting a dissection does not lead to higher recurrence rates.

A second finding was not only reassuring but possibly "practice changing"--that is, even if the sentinel node is positive, omitting dissection still leads to an equivalent and low recurrence risk. This will change practice patterns over time; although for now, it can only be considered to apply to patients who were eligible for this study--namely, patients with two or fewer positive sentinel nodes, breast tumors under 5 cm, and who had lumpectomy and radiation (which covers most of the area of a dissection). However, the trial only accrued a third of its expected enrollment and this weakens the conclusions. On the other hand, the trend was actually better on the sentinel node-only arm, making it very improbable that there would be significantly more recurrences in that arm if the trial had fully enrolled.

A third finding was that the detection of microscopic deposits of tumor cells that measure less than 0.2 mm does not seem to indicate a higher risk of recurrence. This contradicts other studies, but is very compelling coming from a large trial that did enroll its target number of 4,000 patients. The commentator for this presentation at ASCO affirmed that this trial puts an end to the need to test for these deposits that require antibody staining and analysis.

A fourth finding addressed the very old controversial question as to whether nodal dissection actually carries a therapeutic value in addition to providing valuable prognostic information that affects medical and radiation therapy decisions. At least in patients who have a sentinel node dissection, the answer appears to be "no"--there is no added benefit of a node dissection in terms of disease-free or overall survival. In addition, there are less social and work restrictions, arm swelling, numbness, and tingling, as well as better mobility with sentinel node biopsy compared to axillary dissection.

So, this very notable milestone in treatment advance--in this case, primarily to improve quality of life and functionality--is now quite solidified and even raises the number of eligible patients for sentinel node-only surgery. These trials will certainly generate more important clinical and scientific information as their data and tissue banks continue to be analyzed and explored.

You can read more about these two studies presented at ASCO in "Sentinel Lymph Node Studies Considered Practice-Changing."


Yoga: A do-it-yourself treatment program for cancer survivors


While several small studies have suggested the benefits of yoga, ASCO's annual meeting highlighted the largest and most definitive study to date on the benefits of the therapy.

Researchers randomized more than 400 cancer survivors who had significant sleep issues to either simple monitoring or 75-minute yoga sessions twice a week for one month. The results, said lead author Karen Mustian, of the University of Rochester Cancer Center in New York, were remarkable.

The benefits of the intervention were seen across the board, reducing several common side effects reported by cancer survivors. Individuals in the yoga group reported less fatigue and daytime sleepiness, decreased use of sleep medication, and increased quality of sleep and quality of life.

"If you ask a cancer patient who is suffering with sleep problems...who is trying to work, raise children, take care of elderly parents, or live their life in a healthy manner and this is interfering with the ability to live their life...I think these findings are striking," she says. "The fact that we can reduce the amount of fatigue by almost half--42 percent--is huge as well because it's probably the most prevalent and troubling side effect reported by the greatest number of cancer patients across all diagnoses."

You can read the full article on the study here.

The fact the study was so prominent at ASCO, a meeting of oncologists, highlights the possibility that this may be something survivors may be hearing from their doctor soon. "This is a readily applicable approach that improves quality of life and reduces medicine intake in cancer survivors. This is a real positive," said ASCO president, Douglas W. Blayney, MD, at a press conference in May. "This emphasizes the increasing importance of ameliorating complications of therapy in long-term cancer survivors. There are literally millions of patients to whom this might be applicable in the United States."

What's so exciting about this study is that researchers really had the real-world patient in mind. Mustian noted they chose types of yoga that would be most readily available to people in as many communities as possible in the U.S. The two types of yoga--gentle Hatha yoga and restorative yoga--are also gentle on the body and focuses on various poses, breathing exercises, and mindfulness.

"Those gentle Hatha yoga poses are almost in every type of yoga," Mustian says. "By using that, we felt people would have a good chance of finding instructors after the study was done to teach them these poses."

While restorative yoga is less widespread, it's gaining in popularity. For most of the poses, pillows, blocks, towels, and other props are used to support the body. "You're in different positions, but you're fully supported by blankets and bolsters, and your eyes can be covered with eyepads. The idea is to completely let your body be supported by something else," Mustian says. "It focuses a lot on the restoration of balance and really paying attention to your body."

She recommends finding a yoga instructor certified by the Yoga Alliance, and if they have prior experience working with cancer patients and survivors, that's an added plus. She also stressed that these outcomes may not extend to other types of yoga, such as yoga in a heated room or vigorous yoga that raises the heart rate.

You can read more about the different types of yoga at Yoga Journal.

When CURE posted the results on our Facebook page, we discovered that many patients and survivors have already tried the integrative therapy. Here's what a few of our Facebook friends had to say:

"Yoga has kept me moving during a year of surgery chemotherapy and rads. I have good mobility after a partial mastectomy. Pain persists but the gentle yoga approach has allowed me to move as I am able. I see the difference measured in months as I continue to build strength and regain flexibility. It also is very calming to an agitated mind. I suggest a well trained iyengar teacher and not just someone at a gym."--Wendy

"I practice yoga when my body allows me to. As anyone going through chemo knows ... some days it just isn't going to happen. For me, I have intense bone pain following each treatment ... as that begins to subside, I find yoga to be a wonderful retreat ... stretching my legs in various poses and my arms absolutely LOVE being in plank ... feeling strong after periods of such weakness. I find yoga also helps me settle into my body and to notice what is good in both body and mind. I can't practice the full practice that I did before chemo but I find any little bit that I CAN do is wonderful. Sometimes it's hard to be friends with a body that hurts you so much but yoga is a constant reminder that my body is indeed my friend."--Michelle

Do you use yoga either during or after cancer? Did you notice a difference in your sleep or fatigue or general quality of life?

We'd love to hear your personal story of how yoga has affected your cancer journey and what you think of the study!


Amgen's Breakaway from Cancer panel tackles some complex issues at ASCO


Last Friday, Amgen's "Breakaway from Cancer" initiative hosted a star-studded panel discussion at the 2010 American Society of Clinical Oncology annual meeting. The focus was on potential areas for improvement throughout the spectrum of cancer care. Complex topics were covered, ranging from prevention and screening to delivery and access to patient support and survivorship.

Healthcare reform is going to have a tremendous impact on the way care is delivered in the United States. Many uninsured and underinsured families are finally going to have access to quality care, which is a great thing. But what happens when thousands of new patients enter a system that's already maxed-out? Fewer docs are choosing oncology as a specialty, and those currently in practice are struggling to keep up with heavy patient demand. "In order to mount a successful fight against cancer, it's crucial to focus on people who haven't yet become patients. We need a more collaborative approach to prevent cancer," said Carolyn "Bo" Aldige, president and founder of the Prevent Cancer Foundation. She went on to say that half of all cancers would be eradicated if people would make lifestyle changes such as quitting smoking, maintaining a healthy weight, and staying out of the sun. Education is crucial as most people don't realize the power they possess to markedly alter the course of their health.

Screening was another hotly debated topic. Early detection saves lives so why do several effective screening guidelines have yet to be adopted as the standard of care? Panelists blamed the media and agreed that when debates over screening recommendations are hashed out in public, the science is often lost, which gives the public the option of doing nothing. Let's face it... many screenings aren't all that much fun. If no one can agree as to whether getting one actually saves lives, the easiest choice is to postpone the test until a consensus is reached. Not good.

To me, the most interesting topic of the evening addressed the needs of patients once they're diagnosed. How are they being supported throughout their treatment? In many cases the answer is, they're not. Not only do patients need specialists on hand to explain treatment options and next steps, in many cases they need financial counselors, nutritionists, and social workers to help them navigate the journey. "If it's pouring outside, and I have to take two buses to get to my chemotherapy appointment, there's a good chance that I might pull the covers over my head and go back to sleep." said Kim Thiboldeaux, president and chief executive officer of Cancer Support Community. She added that a psychosocial evaluation should be done at the beginning of treatment with checkups along the way to determine how to best meet the needs of patients and their families. This seems simple enough to implement, right? Well, the notion has been met with raised eyebrows because once problems such as depression, financial strain and the like are uncovered, the healthcare provider becomes responsible for getting the patient help for that particular problem,which, as I said early on, they don't have time for!

That leads me to the topic of survivorship. There are 12.5 million of us in the U.S. alone. How are patients supposed to effectively manage the many possible long term and late effects of treatment without having access to specialists whose jobs are to keep their eyes out for warning signs that could lead to recurrence? Ideally, we will be given a survivorship care plan on a pin drive that we'll take with us to our follow up exams. I don't know about you, but I always feel a little guilty taking 15 minutes of my oncologist's time for my annual appointment. I'm 13 years out now, and I know he's busy trying to save the lives of his many patients who are still fighting the good fight. I definitely still go but I rush through the appointment, telling him I'm fine while apologizing for keeping him from more important things. So, here's my idea... what if the government offered incentives to primary care physicians to specialize in cancer survivorship? They would take those calls regarding side aches, depression, and fear of recurrence. They would encourage lifestyle changes and point us to area programs that would support those changes. They'd also take care of all of those screenings we're supposed to get but sometimes avoid.

The Breakaway from Cancer team has some great ideas too. They have developed a nine-step action plan that will soon be made public. Stuart Arbuckle, vice president and general manager of Amgen Oncology, said "We look forward to continuing to work with the Breakaway from Cancer team on initiatives that will continue to drive this dialog, and inspire action in order to provide patients and their families with the best possible care."


A switch in breast cancer’s biology impacts treatment decisions


When breast cancer spread to the liver, a change in the biology of the cancer required a treatment switch for more than one out of every 10 women, according to research presented yesterday at the American Society of Clinical Oncology's annual meeting.

Researchers compared biopsy data from primary breast tumors and liver metastases in 255 women with metastatic breast cancer to see whether the cancer's estrogen, progesterone, and HER2 receptor status--factors that help determine the correct course of treatment--remained the same. Estrogen receptor status changed--that is, the cancer switched from estrogen receptor-negative to estrogen receptor-positive, or vice versa--in 37 patients (14.5 percent). When changes in HER2 status and progesterone status were also determined, a total of 31 patients (12.1 percent) changed treatment to match the tumor's new biology.

"As we have a whole new generation of targeted drugs over the next decade ... it will be that much more necessary to obtain tissue, not just when a woman first has metastatic breast cancer, but potentially over the course of her illness because there is the potential that the cancer can evolve over time," said Eric Winer, MD, of Dana-Farber Cancer Institute in Boston, during a press briefing. Winer was not involved in the study.

"The take-home message is the default position in a woman with metastatic breast cancer should be to perform a biopsy. It's really not performing a biopsy that should be an exception," Winer said.

Melissa Weber is the former managing editor of CURE and is covering the annual meeting of the American Society of Clinical Oncology.


Attention oncologists: talk to your patients about treatment costs


They can talk about sex. They can talk about end of life. But when it comes to the cost of cancer care, physicians aren't talking to their patients.

Although some oncologists feel "economic advisor" isn't part of their job description, the reality is that financial concerns impact the choice of treatment, said presenters during a session at the American Society of Clinical Oncology's annual meeting. A patient's questions and concerns shouldn't be directed at the billing staff because it can restrict the clinical context a physician can provide for making decisions about treatment, said presenter Anthony Back, MD, of the Seattle Cancer Care Alliance.

Research has shown that less than half of oncologists discuss treatment costs with their patients, so the presenters--all oncologists themselves--offered the crowd of physicians practical strategies for communicating with patients. Lesson No. 1: You don't have to be an expert on costs to talk openly to patients and reflect on the choices. Presenters urged their peers to talk to patients about any financial stress that may make it difficult to afford cancer treatment, and to designate an intermediary--for instance, a financial counselor within the practice--to assist patients. And if a treatment is found to be out of reach financially, the physician should discuss alternatives for less expensive treatment when one is available.

As for specific guidance for patients, ASCO's patient website,, offers a downloadable booklet called "Managing the Cost of Cancer Care." Patients can find helpful tips on dealing with financial issues in CURE's 2010 Cancer Resource Guide.

During a question-and-answer session following the presentations, presenter Deborah Schrag, MD, of Dana-Farber Cancer Institute, expressed thanks but also criticism for patient assistance programs offered by drug companies. Although the programs are meant to help patients get access to cancer drugs they otherwise couldn't afford, Schrag said the programs are extremely hard to navigate, which can be discouraging for both patients and physicians, who often give up or don't even try. She called on pharma to simplify the process.

CURE has pulled together a list of assistance programs offered by drug companies, nonprofits, and other organizations. Find it here.

Melissa Weber is the former managing editor of CURE and is covering the annual meeting of the American Society of Clinical Oncology.


New information from sentinel lymph node studies in breast cancer


Over the last decade, the use of sentinel node biopsy has reduced the number of patients who need a full axillary lymph node dissection for treatment and staging of breast cancer.

This represents a very important advance because a sentinel node biopsy is much less likely to lead to long term lymphedema--chronic swelling of the arm that can have a large impact on day-to-day activities and quality of life. However, when one or more sentinel nodes, which are identified by using a blue colored dye and radioactive tracer, are found to contain tumor cells, a full axillary dissection is recommended.

Sentinel node biopsies are done in patients who do not have any nodes felt on physical examination, but about one third of patients who are found to have tumor in the sentinel nodes are currently treated with follow-up complete surgery.

To determine whether additional surgery and its attendant risks are really needed, the American College of Surgeons conducted a trial to see if patients with up to three positive sentinel nodes could be spared a full dissection. This randomized trial compared no further surgery to full dissection in such patients, and the results showed no difference in the number of patients that had a recurrence in the breast or under the arm--about 3 to 4 percent overall, with six years of follow-up.

In the commentary provided on this abstract it was stated that these results are "practice changing" and if adopted, would make a big difference in the side effect profile of breast surgery in the estimated 50,000 of patients who undergo axillary dissection in the United States.


Two drugs top Gleevec in newly diagnosed CML


Gleevec (imatinib), the miracle pill for chronic myeloid leukemia, may soon have some competition after new research suggests two newer-generation drugs, Sprycel (dasatinib) and Tasigna (nilotinib), are more effective in patients with newly diagnosed CML.

Two different studies presented today at the annual meeting of the American Society of Clinical Oncology found that giving Sprycel or Tasigna as first-line therapy resulted in faster, better responses compared with Gleevec.

In one study, after a year of giving newly diagnosed patients either Sprycel or Gleevec, 77 percent of patients on Sprycel achieved a complete cytogenetic response compared with 66 percent of patients on Gleevec. A complete cytogenetic response signals the complete disappearance of all cancer cells from the bone marrow, and achieving this response within a year of starting treatment is associated with better long-term survival, said lead researcher Hagop Kantarjian, MD, of M.D. Anderson Cancer Center in Houston. Sprycel also had the advantage for another marker of drug effectiveness, called a major molecular response: 46 percent versus 28 percent.

In the Tasigna study, complete cytogenetic response was seen in 80 percent of patients on Tasigna compared with 65 percent of patients on Gleevec after one year. The rate of major molecular response also tipped in Tasigna's favor: 44 percent versus 22 percent. Kantarjian, who was also involved in the Tasigna study, said both drugs resulted in fewer "bothersome" side effects, such as nausea, rash, and fluid retention, compared with Gleevec.

Despite the promising results, he said some physicians may want to wait for the three- to five-year follow-up data that will look specifically at survival.

Sprycel and Tasigna are currently approved for CML patients whose disease is resistant or intolerant to Gleevec, which occurs in roughly 30 percent of patients. The Food and Drug Administration is currently reviewing the approval application for Tasigna in newly diagnosed CML, and a decision is expected later this month. Bristol-Myers Squibb, the maker of Sprycel, plans to seek approval for its drug this year as first-line therapy for CML.

And if that wasn't enough, results of a study comparing Gleevec to another next-generation drug called bosutinib are expected by the end of this year, said Kantarjian.

Melissa Weber is the former managing editor of CURE and is covering the annual meeting of the American Society of Clinical Oncology.


ATLAS lung cancer trial fails to show survival benefit


Despite touting one year ago that adding Tarceva (erlotinib) to Avastin (bevacizumab) after initial treatment with Avastin extended the time advanced non-small cell lung cancer patients lived without their disease getting worse, researchers have now found the combination did not help patients live longer. The follow-up data were released today at the annual meeting of the American Society of Clinical Oncology.

CURE first reported on the trial, dubbed ATLAS, at last year's ASCO meeting, but at the time, overall survival data were still to come.

In a poster presented at this year's meeting, investigators reported that although the drug combination delayed disease progression for 4.8 months compared with 3.7 months for Avastin alone, no significant difference was seen in how long patients survived (14.4 months for the combination versus 13.3 months for Avastin alone).

Researchers said that based on this latest analysis, maintenance therapy with Avastin and Tarceva should not be a standard option for these patients.

Read more about the latest options for treating non-small cell lung cancer in "Lung Overdue" from CURE's Spring 2010 issue.

Melissa Weber is the former managing editor of CURE and is covering the annual meeting of the American Society of Clinical Oncology.


Heart disease in childhood cancer survivors linked to gene variations


Childhood cancer survivors who received low doses of anthracycline chemotherapy and who also had variations in a gene called CBR were more likely to develop heart disease than survivors without CBR gene variations who received low doses, according to research presented today at the American Society of Clinical Oncology's annual meeting.

CBRs, or carbonyl reductases, help metabolize anthracycline drugs into substances that can damage the heart. The activity of CBRs can be affected by variations in the CBR-producing genes CBR1 and CBR3, both of which were used in the study to determine the risk of heart disease.

Researchers compared 165 survivors who developed cardiomyopathy, in which the heart doesn't pump effectively, with 323 survivors without heart disease. Most of the patients included in the study were treated after 1981, with a median age of 7.5 years at diagnosis.

For survivors treated with high doses of anthracyclines, the CBR gene variations didn't have much effect on the risk of heart disease because the high dose meant the risk was already high. But for those who received a low anthracycline dose, carrying the CBR1 gene variation resulted in a 5.3-fold increased risk for cardiomyopathy compared to those with the low-risk gene variation. Survivors with the CBR3 gene variation had a 3.1-fold increased risk.

"Although we depend heavily on anthracyclines for treating children with cancer, we are fully aware of their toxic effects to the heart. We also know that some patients--despite being exposed to higher doses--don't develop heart problems, while others with little exposure have considerable cardiac damage," senior author Smita Bhatia, MD, of the City of Hope National Medical Center in Duarte, California, said in a press statement.

More research is needed, Bhatia said in a press briefing prior to the meeting, but if the findings hold, she said pediatric oncologists can use a personalized approach based on knowledge of the patient's genetic makeup. She said children with cancer could be screened for these gene variations before treatment, and therapy that doesn't include anthracyclines could be considered for patients at risk for heart disease.

The mechanisms behind the CBR gene variations and increased risk for heart disease are the same in adults as in childhood cancer patients, said Bhatia, adding that her institution is currently doing similar research in adults.

Because childhood cancer survivors can experience various late effects of cancer treatment, the Children's Oncology Group developed follow-up guidelines that provide recommendations for screening and management of possible late effects. The guidelines can be downloaded at

Melissa Weber is the former managing editor of CURE and is covering the annual meeting of the American Society of Clinical Oncology.


ASCO Update: New frontiers in personalized medicine--the Human Genome


One of the themes of this year's ASCO program reflects the increasing use of biology in making treatment decisions, an idea that just a decade ago was thought to be fantasy--something we would not really see in our lifetime. However, we have already adopted gene testing and molecular profiling in the clinic. The next chapter of sequencing the whole genome of a tumor has just opened with a flurry of publications in the last two years and the formation of diagnostic companies that plan to offer these commercial services--even though most of the sequencing information is not ready to be used in the clinic.

At Saturday's breast cancer poster discussion session, there were some early looks at what this future field might look like. One trial in patients receiving the HER2-blocking drug Tykerb (lapatinib) suggested that inherited variants of certain genes involved in HER2 signaling might affect outcome--specifically the cyclin D1 gene, which is involved in cell cycling and can be amplified in breast cancer.

Another study refuted earlier findings that acquired mutations (only in the tumor) in the signaling protein PI3 kinase might predict resistance to the experimental HER2-based immunotoxin T-DM1. These early findings need more confirmation in larger trials, but mostly likely, there will be a second generation of markers that tell us specifically which drug will be most effective for which cancer, especially for targeted agents.

This point was hit home much more dramatically in today's plenary session for a small subset of lung cancers (about 5 percent of all lung cancers) that harbor an altered gene called ALK and treated with crizotinib, an investigational inhibitor of the kinase encoded by this gene.

An astounding 57 percent of patients exhibited a response--much higher that typically seen with any regimen. This is an example of such a strong leap in gene testing and targeted therapy that the discussant who commented on this abstract implied that a randomized trial for this agent might not even be needed. Already, testing for ALK is available in some centers and commercial labs, and very soon, detailed genetic testing on lung cancer will become routine for both approved treatments and for choosing the right clinical trial.


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