Cognitive functioning in breast cancer patients

A new study on chemotherapy and its effect on the brain will be presented at the annual conference of the nation’s chief oncology group in Orlando. ASCO — the American Society of Clinical Oncology — has posted brief synopses of research, known as abstracts, online. (The meeting starts May 29. Late-breaking abstracts will be posted May 31.) The list is searchable by key word, and is good raw material for someone who wants to dive more deeply into the science of cancer and its treatment. At most conferences, new research is presented in several formats: as posters that are pinned up on boards in a large room, as an oral presentation on stage in front of an audience, or in a smaller panel or talk. The rigors of scientific research demand statistical analysis that may seem befuddling, even to those who took statistics in college. And researchers may use terms that seem arcane. But Google can be a powerful tool, making it relatively easy to search for definitions. Look for authoritative, official websites that have information vetted by doctors or researchers or science writers. For basics on cancer, or on study methodology, the National Cancer Institute website, found here, is clear and authoritative. Dig deep, and you can find an explanation for many medical and scientific terms.

One study being presented at the ASCO conference addresses cognitive functioning in breast cancer patients during and after chemotherapy. The study, done by researchers at the University of Rochester Medical Center in New York, was an outgrowth of another study of the antidepressant Paxil, which I blogged about here. Researchers looked at the changes that breast cancer patients reported over four cycles of chemotherapy, and then looked at how they were doing two years later. In all, 84 patients completed questionnaires about whether they experienced heavy headedness, muddled thoughts, difficulty thinking, trouble concentrating, or forgetfulness. (Patients filled out the questionnaires seven days after each treatment.) In all, 58 patients answered questions after all four cycles. Cognitive difficulties were highest after the first chemotherapy cycle, and were significantly improved by the third and fourth cycles.

But the researchers also found that there was an increase in cognitive difficulties AFTER the last cycle for a few patients — but not enough to be statistically significant. In other words, a very few patients found that their cognitive problems worsened after chemotherapy ended. Some patients reported improvements, and some reported no change.

The conclusion? The University of Rochester research suggests that cognitive difficulties related to cancer treatment are most pronounced after initial cycles of chemotherapy treatment, and that they improve during the treatment course.  As always, this research is simply a guidepost along the pathway, one more dollop of information that may ultimately lead to a deepened understanding of chemobrain. Better testing is needed — paper and pencil tests that allow doctors and patients to track symptoms, paired with brain scans and tests that measure other biological processes.

“Further studies need to include objective neuropsychological examinations and biological correlates of cognitive functioning to understand the extend of cognitive decline due to chemotherapy,” the researchers say.

Elizabeth Neuffer

NEUFFERI am packing up my office at the Boston Globe, preparing to move to the Broad Institute in Cambridge on June 8. A rush of memory and nostalgia is inevitable.  I found a French backpacking guide — wedged into the back of a bookcase — from a trip I took in 1995 with Elizabeth Neuffer, who was covering the war in Bosnia for the Globe. Neuffer, also a childhood friend of my partner, Ellen Zucker, was on hiatus from the war, taking time to tour with her father. By the time she met us in the south of France, she was ready for a few laughs.

We took the fast TGV train to Marseille, met Elizabeth, and, for lack of a better mode of transportation, asked a cabbie to take us to the French Riviera town of Cassis. As the cab lurched along, we picked an inn from Le Guide du Routard, the French backpacking guide we had bought in Paris. Elizabeth and Ellen Zucker both spoke French, and had no problem leafing through it. I could read a bit, thanks to years of high school Latin and numerous dinner-table quizzes about cognates. The cab dropped us at a rental car office outside Cassis, and Elizabeth and Ellen Z. haggled over the price of a tiny Renault. There was room for two adults and luggage — I lay across the luggage on the back seat. After a bone-rattling ride, our accommodations hove into view: The Hotel France Maguy, bright pink, with some rooms that went for the equivalent of $25 a night. Because it was off-season, and because it was perhaps on the low end of the luxury scale, we were the only guests and had our choice of rooms: small,  smaller, smallest. Some of the hotel doors were missing, but the Dutch hippie proprietors had put up colorful shower curtains in their place. That was fine by us. With no doors, and no guests to object, we could shout jokes between the rooms as late as we wanted.

We dropped our luggage and headed for town, where we bought bread, local cheese, tomatoes, olives, and a cheap rose. By now it had begun to rain, but we were determined: we had a picnic on the beach. Soaked to the skin and slightly tipsy, we got back to the Maguy to find that the proprietors had set out generous bowl-size lattes — a treat because we had put ourselves on a coffee diet in Paris to save money.

We had plenty of laughs, toured the craggy calanques on the coast, played boules on the town green — all in the incessant rain —  and got to know the owners of the Maguy over the next few days. The owners rode into town every morning on their bicycles and brought back fresh croissants and fruit for breakfast. We scoured the local flea markets and gossiped and generally tackled the problems of the world over numerous bottles of the local wine. It was a seemingly carefree respite, despite the rain, despite her father’s encroaching illness and despite the fact that she would be returning to her coverage of war and disruption.

Elizabeth, of course, went on to win numerous awards for her reporting in Bosnia and in Rwanda, including the Novartis Prize for Excellence in International Journalism and the Edward R. Murrow Fellowship from the Council on Foreign Relations. Her  book, “The Key to My Neighbor’s House: Seeking Justice in Bosnia and Rwanda,” documents her search for justice for the disappeared. She seemed to be in a place in her career where she was ready to give up reporting from war zones in favor of a more settled life. When the war in Iraq appeared to be winding down, in April 2003, she made a trip to report on the aftermath. The struggles and dreams of ordinary people had always interested her more than combat, at any rate. Always cautious, she ventured out on May 9, 2003, with a trusted driver and translator to Tikrit to gather string for a Sunday story on the Ba’ath Party. On the trip back to Baghdad, the car struck a guardrail. Elizabeth, 46,  and her translator, Waleed al-Dulaimi, were killed.

I recently stumbled across a link to a forum at the Kennedy Library where Elizabeth and Samantha Power talked about their work on genocide. The forum was in February 2003, three months before her death. The International Women’s Media Foundation, which gave Elizabeth the Courage in Journalism Award in 1998, established a scholarship in her name that continues to survive, despite the downturn in the newspaper industry. I often wonder what Elizabeth would make of the current state of affairs in journalism, her passion.  As someone wrote on the obituary website: When Elizabeth died, it was another bad day for the truth.

2009 Oncologists’ Meeting – Preview

ASCOOncologists gather in Orlando on May 29 for the annual meeting of the American Society of Clinical Oncology. ASCO posts short takes of studies, known as abstracts, online. I’ve combed through the list in order to highlight a few that touch on chemotherapy and cognitive dysfunction. I’ll present them here in small bites.

The first, from researchers at the University of Rochester Medical Center, examines the effectiveness of pharmacological interventions to control chemobrain symptoms. The researchers do not actually use the term chemobrain, of course. They call it cancer-related cognitive dysfunction, or CRCD. “Cancer and its treatment impact important areas of cognitive function such as attention and memory, which are essential to patients’ effective psychosocial functioning and quality of life,” the researchers report in their study, entitled “Neuroprotective effect of SSRI among 781 cancer patients receiving chemotherapy.”

From 17 percent to 75 percent of cancer patients report some difficulty with thinking and memory during and after treatment, the authors note. But few studies have looked at whether drugs prescribed for other ailments might help. This study, which is scheduled to be presented at the ASCO convention on Saturday, May 30, studied whether the antidepressant Paxil (paroxetine hydrochloride) helps with memory problems. Paxil, manufactured by GlaxoSmithKline, is an SSRI — selective serotonin reuptake inhibitor — that is commonly prescribed to treat anxiety disorders, among other conditions. (SSRIs help balance the level of serotonin, a neurotransmitter, in the brain.) The researchers gave patients a test to measure their memories. Patients who were tested ranged in age between 22 and 87 — a range that captures the brain in all its seasons. Of the patients tested, 574 were women, and 207 were men.

Patients were given the memory test after their first chemotherapy cycle and before being given Paxil, and then tested again after they had received four cycles of chemo and had been given Paxil. Some patients received placebos, or inert sugar pills, instead of Paxil. The researchers found a significant different between memory test scores before Paxil and afterward. Not surprisingly, they also found that Paxil relieved symptoms of depression that can also plague cancer patients before, during, and after treatment. (Other studies show that depression and stress can also affect cognition.)

The bottom line? The study says that cancer-related cognitive dysfunction “is a serious problem for patients that can be alleviated by Paxil. Future studies should examine the usefulness of other psychotropic agents and combined behavioral and pharmacologic interventions to control [it].”

Of course, this is one study of many that look at chemobrain. As always, no course of therapy should be undertaken without asking your doctor.

Chemobrain in the Irish Times

Lucy Atkins’s article on chemobrain for the Guardian in the UK struck a chord. It was picked up by the print edition of the Irish Times. Here are some reader comments.

Re: Cancer Fallout, Healthplus, April 28th

Dear Sir,

I read an article in Healthplus about cancer fallout which was very interesting to me as a cancer survivor.

Even though the section was about breast cancer, a lot of the after effects experienced by these women are similar to mine. I am a 28-year-old male who was diagnosed with non-Hodgkin CNS lymphoma in 2005.

Although four years on, this type of cancer is treatable, I went through all the treatment and am now in remission. But the fallout and side effects from it still make me worry that it might come back again because some of the symptoms that I presented with have not gone away, but the doctors have told me everything is fine from the scans that have been done.

As some of the women who had breast cancer and survived say in the article, the after effects of chemotherapy can be very difficult to live with.

Like the women who were describing some of the after effects of chemo on the brain, I too have had similar effects as well.

These include being forgetful and misplacing items, forgetting people’s names, etc. Sometimes I can’t remember certain things that happened just a few days ago – even if someone asks me if I remember certain things that we did last week.

Sometimes I have to go back to check whether I locked the front door when going out, only to find that I did, or having to check whether I rolled up the window in the car.

All these small things would drive a person mad. Sometimes when people are talking I have to say yes to them, to keep up with the conversation about something that happened. I could be trying to think of it, but just cannot remember it happening.

It can get so irritating at times that I ask myself is there something wrong with me that I can’t remember.

Confidence levels drop and sometimes one might get into a depressed state for a few days and get upset with people asking, “Are you all right, what’s wrong, can we help?”

You can get angry with yourself that you are unable to explain to them what’s going on when you don’t even know yourself why this is happening, but you get back out of this depressed state when something needs to be done.

There are also times, like now, where I have thought of something to say and I’ve forgotten it already.

Small little things like that can get a person down. Life can be difficult but we just have to keep going and try to put it to the back of our minds.

Any other information on chemobrain, or any information on where to obtain it, would be greatly welcomed.

Yours etc,

Conal Sadler,



Co Mayo .

Dear Sir,

I had a mastectomy in August 2006 followed by chemo which finished in early 2007 – and to this day I can stop mid-conversation completely lost for a simple word.

I always say it is “chemobrain”, much more impressive than the so common “senior moment”! I do think it is a problem, much the same as being told that you may suffer from tiredness from chemo, whereas from what I gather it affects everyone.

Tiredness is not the right word for the utter fatigue I experienced.

Yours etc,

Anne Vaughan,

Templeville Drive,

Dublin 6W

Globe deputy editor going to Broad Institute – The Boston Globe

Reader comment

I am sitting here at my computer crying because I have been so affected by chemo brain and I have not been able to return to work. I live in northern Ontario, in Canada. There seems to be very little info about chemo brain and my employer has so much as said that I am making it up so as not to have to return to work. I work in a fast paced medical laboratory, and multi tasking is a must. I can barely function in my kitchen. I finished chemo for breast cancer in Nov. 2008 and I am 45 years old. My main problem is with very short term memory. I can perform a task and then minutes later not have any recollection of doing it. I grasp for words and have trouble spelling. Many times I know I need to accomplish something, such as putting on my seatbelt but I cannot figure it out immediately. I sit for a minute, and then it is like a slow-moving train coming around the mountain – Oh yeah, I need to do this. I am so frustrated trying to defend the fact that this is real. It was easier when I was bald and looked outwardly sick. At least then I felt I had credibility as to my illness.

Thanks for listening. Debbie Irwin

Chemobrain vs. smog in LA

A reader writes…
I am always bemused when the medical establishment finally catches up with what everyone has been saying for a long time.  All you have to do to know about chemobrain is go on chemo. I met countless other women on planes, buses, etc. while I was on chemo, who all experienced it.
Somehow we could instantly sense each other. It usually took about 15 seconds after saying hello to a total stranger to find myself deeply immersed in a conversation about how chemo was making it hard to think.  But it is good that now the doctors will believe us.   And it is good to live in L.A. and So. Cal. where everyone is a bit scattered. I have no idea by now what is chemobrain, what is information overload, what is smog, and what is being post menopausal.
Margie W.

NCI to boost Cancer Genome Atlas


Speaking to an audience of cancer researchers and clinicians at the American Association for Cancer Research, the director of the National Cancer Institute colored in some of the details of how his agency intends to spend its share of the federal stimulus windfall.

After four years of flat-funding, the NCI will pour much of the $1.3 billion into seeding a next generation of cancer research and into expanding the three-year-old Cancer Genome Atlas, according to director John Niederhuber.

The money, part of President Obama’s $787 billion American Recovery and Reinvestment Act, is targeting genetic and cancer research in part because of the efforts of US Senator Arlen Specter, a cancer survivor who is interested in translational biomedical research. In other words, Specter is pushing for the kind of science that can leap from lab bench to bedside.

When it became clear that NCI was due for a significant share of stimulus money over a two-year period (2009 and 2010), Niederhuber and his colleagues took a moment to weigh all the demands — to assess what Americans want in terms of next steps in the so-called war on cancer.

niederhuber1“We came back repeatedly, in these discussions, to the conclusion that they want better ways to prevent cancer; they want the earliest diagnosis; and they want new therapies with fewer side-effects that turn cancer into a condition you can live with and not die from,” he told the conference in his talk on April 20.

Then, he sketched out a broad vision. “Economic stimulus funds give us the chance to be visionary; to make strides today toward realizing the promise of personalized medicine; to enhance the process of drug development from target identification to translation into viable therapies; to move cancer research from the accumulation of scientifically exciting genomic data to a new way of approaching prevention, diagnosis, and therapy and to ensure access to our latest science for all.”

Mindful of Obama’s command to “ignite our imagination,” Niederhuber says the NCI has an eye on the future: fostering a next generation of cancer science and cancer scientists. To that end, the agency plans to award grant money to young investigators who are MD-PhDs, “who are committed to careers in translational cancer research.”


The money will supply some rocket fuel to The Cancer Genome Atlas (TCGA), launched in 2006 by the NCI and the National Human Genome Research Institute. Since then, Niederhuber says, TCGA has sequenced more than 200 tumors in the brain (glioblastoma), and in lung cancers and ovarian cancer.

“With that foundation of success,” he said, “we plan to move TCGA forward, with a goal of identifying all of the relevant genomic alterations in 20 to 25 major tumor types.” Another NCI program, called TARGET, will get money to expand sequencing to 100 tumor types in childhood cancer. (In the realm of NCI acronyms, TARGET stands for Therapeutically Applicable Research to Generate Effective Treatments.)

Translated into bottom lines and budgets, the stimulus package means money for science: new equipment, and salaries for lab technicians and post-doctoral students who work, like chefs in an exquisite kitchen, with the raw ingredients of life. Mindful that research begun with stimulus funds must be continued beyond the two-year window, the Niederhuber remains an optimist.

Although the TCGA has been criticized by those who believe it is too expensive, inefficient, and likely to lead to descriptive studies rather than real breakthroughs, Niederhuber and his colleagues believe this kind of research is a blueprint for the 21st century. It is, in effect, all about drawing a clear, bright line from discovery to the patient, from the molecular view to the whole of a person.

“This wide-ranging plan will require the contributions of biologists, chemists, informaticians, and clinical scientists who are devoted to a clear path from discovery to patient. that is not only the nature of translation; I believe it will be a model for the study of many diseases and, ultimately, a model of 21st century healthcare, when we are able to match pharmacogenomically characterized patients and molecularly profiled tumor types to highly specific molecularly targeted therapies.”

A pause for inspiration

Michael Paulson, the Pulitzer-prize-winning religion reporter for the Boston Globe, links to some thoughtful and spiritual comments on Susan Boyle, the Scottish singer who stunned the cynical panel of “Britain’s Got Talent.”

When Boyle tottered onto the stage, the audience and the judges were rolling their eyes and stifling laughs. She is (pick one): not blonde, not young, not thin. But her performance put everyone to shame.

As Michael asks, what does it say about our culture?

Here is the link.

Dr. Dietrich on chemobrain, part 2


Part two of a Q&A interview with Dr. Jorg Dietrich, a neuro-oncologist at Massachusetts General Hospital. Dr. Dietrich believes that DNA damage to progenitor cells in the brain could play a role in chemobrain. Here, he focuses on the doctor-patient relationship.

Q. How do you approach the discussion when you are talking with a patient?
A. I think one of the main obligations we as oncologists have is to openly discuss the treatment options and all possible associated side effects, even if these are not common. It will have to be accepted that the brain is one of the targeted areas of toxicity and cognitive symptoms may just not be the result of chronic fatigue and depression, as it has been thought initially. We will not be able to avoid chemotherapy and radiation as part of cancer therapy. But I think that it is important to openly discuss all possible side effect profiles to alert patients and their families of potential outcomes of toxicities to the brain and then also to define ways of better monitoring and treating side effects once they occur.

And I think once we define the clinical problem and we know what we are looking for, then it is only a matter of time before we identify the best mechanisms to protect the brain. If no one really looks at the problem, for example to defining the cell populations at risk, then no one will look at protective strategies either because the problems have not been outlined and characterized.

Q. What interested you in this field of medicine?
A. This is a fascinating field to be in. In the past five years, this has really been a hot topic and a problem that affects more people than anticipated. And I think it is really important to further create awareness but also to help patients understand their symptoms because many times they have been without answers. Doctors would say, “Well, you’re just depressed, you’re just fatigued and that’s why you don’t concentrate so well and you’re not attentive as much as you used to be or you were able to multitask and you just can’t do it anymore.”

So there has been all this mystery, coupled with poor explanations, and I think it is our job as physicians to really help patients along and also to support them, as symptoms may come up to deal and to cope with deficits as opposed to just not mentioning or neglecting these. As much as we increase our understanding in this field, it is also important to emphasize that patients should remain encouraged to go on with their treatments. It was never our intention to create contradictions or doubts in a sense that patients would say, “Well, then, we “don’t even want the treatment.” Because I think one has to be careful with creating uncertainty in patients.

Q. Have you encountered that clinically?
A. I think I’ve heard it in comments and in the reviewing process of several scientific articles. Personally, on a patient basis I have never encountered it, because I think the more we are open about alerting patients to potential side effects — to the bone marrow, kidneys and liver — patients usually are accepting of them. And I think if you include just the brain as a potential site of toxicity and say there may be trouble down the road with cognitive issues, you may not be as highly functioning any more in your capacity to do math, calculations, etc., I think if patients know about it they will accept the situation. As opposed to retrospectively to finding out and then to have no answers for what really happened.

Q. So you believe in a degree of openess, but putting it in context.
A. Exactly. I think we treat to the best of our knowledge because survival and quality of life are the highest aims.  We have to really be on the side of the patient to understand what their needs are. I think this is one of our main duties — to balance risks and benefits and to advice patients appropriately when toxicities are unacceptable and life expectancies would be limited anyhow. I think these are the moments when we should use our judgment and advise patients appropriately.

Q. Have you gotten a lot of reaction to this study?
A. Yes, a lot. What has been sometimes saddening to hear is that many patients and their families have now have found answers to unexplained symptoms they encountered for many years.  Nobody knew why they felt that way because the brain was not even targeted. They had received chemotherapy for breast or lung cancer, for example. And then all of a sudden to have clouded memory, fuzziness, not feeling right, and nobody had really been able to pinpoint this… so I think to provide answers is a big relief. The next step is certainly to deal with the symptoms and to help the patients to feel better.

This all remains a delicate issue. I think it is critical for everyone publishing about this topic to keep in mind how important it is to balance provocative thoughts on the one hand, and to be reassuring to patients on the other hand. Our intention is to help and to find means to properly deal with these problems as they occur. As we gain a better understanding of the physiology of nervous system toxicity, we will get closer to counteracting and developing protective measures for the brain. I think it is only a matter of time before we reach this point, as certain agents already exist.

Q. What exists now that can help?
A. I think what is very beneficial in some patients are high-dose antioxidants. These agents generally have a positive effect on brain repair and progenitor cell populations. The downside is that antioxidants may impair the effectiveness of chemotherapeutic agents, when given at the same time. This is part of our current investigations. Physical exercise is extremely important, so I always encourage my patients to break that cycle of fatigue, because the more they become inactive, the more the brain suffers. So we know that just walking or running is one of the strongest stimulating factors for brain plasticity. It is a very provocative thought, and I think this has been very well studied by scientists who extensively looked at the problem of brain repair and the generation of new neurons. And physical exercise is, interestingly, one of the strongest factors in maintaining brain function.

That’s a whole different topic I could talk to you about from the aspect of brain development, brain plasticity and maintenance, even outside of any disease paradigm. For healthy individuals this seems to be extremely beneficial. So a healthy diet, rich in fruits and vegetables, and exercise. These are essential in order to at least give the brain the tools to be able to repair itself. If there are deficient areas to begin with, the patient’s recovery will already not be at the optimal level. There are a number of agents that we are currently studying in experimental paradigms; although these are not ready to be used in clinical practice yet, I think it’s a matter of probably three to five years until we have quite good agents available to treat patients along with their chemotherapy.

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