By Kathy LaTour

Three weeks before my last chemotherapy treatment‚ I was standing in the cereal aisle at the grocery store. Like most women undergoing treatment for breast cancer‚ I had other things to do in the midst of the life-changing event that is a cancer diagnosis.

A breast cancer diagnosis doesn’t mean that the children‚ in my case a 1-year-old and a teenage stepson‚ don’t have to eat. So there I was‚ staring at the cereal and hoping it would remind what I had come to buy.

What used to be weekly‚ meticulously organized trips to the grocery store had become frequent stops to pick up some forgotten item. And this wasn’t the first time I had found myself wandering the store‚ hoping something would trigger the memory of what had‚ only minutes before‚ been desperately needed. My family had gotten used to cereal without milk‚ stew without carrots‚ and mom without a memory. I had gotten used to the frustration of feeling like I had not only lost a breast but also a good portion of my mind.

In my support group‚ where we laughed and cried about how our lives and bodies had been rearranged since breast cancer‚ we called it “chemocurse” or “chemobrain”‚ that foggy twilight that had swallowed the names we used to know‚ the location of the keys‚ the day of the week‚ and sometimes‚ entire conversations. We chalked it up to one of the many changes wrought by cancer‚ some of us blaming it on “chemopause‚” the chemotherapy-induced menopause that temporarily—or permanently—removed estrogen from our bodies.

More than once a friend would say‚ “God‚ I am turning into my mother. She used to get the children’s names mixed up just like I do now.”

Others in the group blamed it on the anxiety of having cancer and the uncertainty such a diagnosis brings—along with anesthesia‚ hospital stays‚ and fear. Few of us had any comparisons in life to this experience. Maybe facing mortality brought with it this mental fog to somehow protect us. Mostly‚ we all just commiserated‚ told stories‚ and agreed that we all had it‚ and it was real‚ no matter the cause.

That was in 1987. Today the baby is a teenager‚ the teenager is a father‚ and researchers have found that the cotton-candy brain we called chemobrain is a real condition called “cognitive dysfunction.”

I can hear the chorus of breast cancer survivors across the country screaming‚ “We told you so.”

Cognitive Dysfunction
Cognitive dysfunction refers to a veritable smorgasbord of “neuropsychological” impairments with loss of memory‚ difficulties with language‚ and lack of concentration being at the top of the list. Many of us complained of losing an edge required to do the multitasking required of today’s modern woman. Tracking a single effort to completion took effort; more than one seemed out of the question.

It’s not that we didn’t tell the doctors we were feeling less than normal‚ and it’s not that our doctors didn’t believe us. It’s just that the doctors didn’t know how to assess it. They saw women who were having symptoms that could be attributed to a number of causes. At the top of the list was estrogen withdrawal either from chemopause or stopping estrogen replacement therapy‚ which could cause impaired memory and concentration.

Add to that list the possibility of depression‚ which can also cause the same symptoms‚ and you have another cause. With other everyday issues such as normal aging‚ sleep deprivation‚ and panic brought on from anxiety‚ doctors and survivors alike said‚ “Well‚ it’s all part of the deal.”

To confuse the issue further‚ there were some women who just didn’t understand what we meant; they clearly had not been affected at all.

But in the late ’90s‚ the neuropsychologists began studying the phenomenon. The first study‚ led by Frits van Dam‚ PhD‚ and Sanne Schagen‚ MA‚ at the Netherlands Cancer Institute in Amsterdam‚ compared patients with high-risk breast cancer who were assigned to receive either high-dose chemotherapy or standard-dose adjuvant chemotherapy plus hormonal therapy with Nolvadex®(tamoxifen). Patients were interviewed with regard to cognitive problems‚ quality of life‚ and depression. Results from these groups were compared to another group of breast cancer patients who had early-stage breast cancer that was not treated with chemotherapy or Nolvadex. The women were all studied two years after treatment ended.

Their findings were that 32% of the patients treated with high-dose chemotherapy and 17% of patients treated with standard-dose chemotherapy had cognitive impairment when tested with standard neuropsychological tests‚ while only 9% of the control patients showed impairment. This led to the following conclusions:

1. Breast cancer patients treated with adjuvant chemotherapy had a higher risk of cognitive impairment than women with breast cancer who did not have chemotherapy.
2. The impairment was unaffected by anxiety‚ depression‚ fatigue‚ or time since treatment.

The Cause
U.S. researchers‚ who began following up the first study with their own‚ confirmed the findings. Clearly‚ chemotherapy was doing something to the ability of the brain to function‚ but what?

While researchers are the first to admit they don’t know exactly what is happening‚ the discussions are leaning toward frontal lobe issues that are the same as those that are seen in regular aging.

Joyce O’Shaughnessy‚ MD‚ director‚ Cancer Prevention Program and codirector‚ Breast Cancer Research Program at Baylor-Charles A. Sammons Cancer Center and US Oncology in Dallas‚ Texas‚ says that while there is growing acceptance that the issue is real‚ the studies have only involved women with breast cancer and have been limited in scope.

“We all feel in our guts that there is something to this‚ but we have to be careful since we have very little data‚ and we don’t know the role menopause plays‚” she says.

Charles Loprinzi‚ MD‚ at the Mayo Clinic in Rochester‚ Minnesota‚ who has studied quality-of-life issues associated with chemotherapy‚ agrees that cognitive dysfunction is being recognized by the medical community as a real phenomenon‚ but its prevalence and severity are yet to be determined.

For women like Diane Balma‚ it comes as no surprise that chemobrain is real. And for professionals such as this public policy attorney‚ the lingering effects can be frustrating.

Balma was a busy 29-year-old attorney in San Francisco when she was diagnosed with breast cancer in 1996.

“During chemotherapy I knew that something was different‚” Balma says. “My grandmother had come to California to care for me while I recovered‚ and I can remember asking one day if I was supposed to sign my check. Really‚ I couldn’t remember.”

Balma‚ who today travels frequently to Washington‚ D.C.‚ as a public policy specialist‚ says she still has moments when words will not come to her but finds her analytical ability unaffected.

“I have had to search for words that had always been there. I was an excellent speller before cancer‚ but today‚ I still occasionally have a moment when a common word will confuse me. Mostly it’s just an inconvenience‚ but when you are a professional and words are your business‚ it can be very frustrating.”

Other women have similar complaints: words are gone when they used to be there‚ names stay on the tip of the tongue‚ details get lost‚ and sometimes‚ at its worst‚ children are forgotten.

One friend confided that she didn’t know how complicated her life was until she could no longer keep up during chemotherapy. Like many of us‚ she saw herself as the modern‚ do-it-all mom. During breast cancer‚ managing her two small children‚ one an infant‚ became overwhelming.

“The worst was the day I forgot to pick my daughter up at day care. I just simply forgot. I couldn’t believe it. I forgot my child and I felt so awful. For me and for lots of other women‚ knowing that this is physiological will do a lot to alleviate the guilt we feel when we just seem to be out of it.”

Finding a Solution
Dr. O’Shaughnessy agrees that it’s a quality-of-life issue for women. And‚ while the why of chemobrain is still an unknown‚ her focus now is a way to improve the situation for women who are already undergoing a very traumatic experience. She has just completed a study on the role erythropoietin‚ the natural substance created by the body to increase red blood cells‚ may play in preventing cognitive dysfunction in women with breast cancer who are undergoing chemotherapy.

“Erythropoietin is made in the kidneys‚ which is also the body’s anemia-sensing organ. So if you are in a car accident and bleeding out and your blood volume is going down‚ the kidney senses it and makes more erythropoietin‚ which stimulates the bone marrow to make more red blood cells.”

While this has been known for decades‚ the newest finding is that there are erythropoietin receptors on nerve cells‚ and erythropoietin is also made in the brain‚ where it is found in increasing levels when someone has had a transient ischemic attack (TIA)‚ a warning sign of stroke. This information translates into erythropoietin being a protector of the brain cells or brain function when there is a decrease in oxygen supply to the brain. Since it appears erythropoietin might protect brain cells from injury and death in the face of decreased oxygen‚ it was reasoned that perhaps erythropoietin could protect brain cells from the toxic effects of chemotherapy.

Dr. O’Shaughnessy’s recent study compared cognitive dysfunction in women undergoing chemotherapy who were given weekly erythropoietin injections to those receiving placebo. Procrit®‚ the drug form of erythropoietin‚ has been approved for use when hemoglobin levels indicate a patient is anemic as a result of chemotherapy.

“Procrit has been looked at in a pilot study in Germany for people who have had strokes coming into the emergency room‚ because‚ in mice‚ if you start Procrit within six hours of a stroke‚ you lose significantly less brain. What it appears Procrit does is raise the injury threshold at which cell death occurs‚” she says.

Dr. O’Shaughnessy says that findings may eventually mean the use of Procrit before anemia sets in to protect the brain for women starting breast cancer chemotherapy. But Dr. O’Shaughnessy stresses that it’s still too early to make any recommendations since the results of the study are not yet available.

“We know from a couple of trials that women receiving adjuvant breast cancer chemotherapy along with erythropoietin definitely feel better and have more energy and a better quality of life.”

Dr. O’Shaughnessy studied women’s cognitive dysfunction in the middle of their chemotherapy compared to their prechemotherapy cognitive function. She used a standard developed by neuropsychologist Don Royall‚ MD‚ professor of psychiatry at The University of Texas Health Science Center at San Antonio‚ who studied the normal aging process of retirees. Dr. Royall developed a test called the “EXIT25‚” which measures “executive function‚” or‚ as Dr. O’Shaughnessy defines it‚ “the ability to string together simple things into complex behavior.”

Dr. Royall developed a test of 25 items to measure the association between brain aging‚ executive control dysfunction‚ and asthenia‚ which Dr. O’Shaughnessy used for her study.

“Asthenia is the fatigue that only cancer patients know‚” Dr. O’Shaughnessy explains. “It doesn"t get better with sleep. You wake up tired. You are tired at rest; you are tired thinking about doing anything.”

The example Dr. O’Shaughnessy gives for executive control function is one that many women recognize. “She has two or three kids that she has to get out of the house in the morning. She also works. So‚ she’s got to get the kids up and dressed and fed‚ and all of their stuff has to be with them when they leave the house. They all have to be someplace on time. That’s a yeoman’s job and‚ if you can’t remember in the middle of something what you’re supposed to be doing‚ that’s executive control—monitoring what you’re supposed to be doing and remembering what you"re supposed to do next.”

Dr. Loprinzi and his colleagues at the Mayo Clinic became interested in cognitive dysfunction while studying other side effects of chemotherapy (see preceding page). “We have been involved with a number of trials looking at side effects of chemotherapy: mouth sores‚ hot flashes‚ appetite troubles. We have also done a number of trials looking at herbal preparations and complementary issues. With interest in both areas‚ we decided to look at the cognitive dysfunction issue.”

Dr. Loprinzi’s team‚ with a project led by his colleague Debra Barton‚ RN‚ will be looking at possible benefits for cognitive dysfunction with the herb Ginkgo biloba in a new trial this year through North Central Cancer Treatment Group.

“There is information suggesting that it might be helpful for Alzheimer’s dementia. So‚ if it"s a thinking problem‚ we want to see if it will work with chemotherapy-induced dysfunction. We have no proof that it will work‚ but it has shown some benefit in other forms of dementia.”

Both Dr. Loprinzi and Dr. O’Shaughnessy stress that all research in the area of cognitive dysfunction is very early. “It appears that this is a real phenomenon‚” he says‚ “but how common and to what degree are to be determined. But now it’s on the radar screen‚ and in the trials we will be obtaining more information about this phenomenon and‚ hopefully‚ learning about what kinds of things will help impact it.”

This is good news for women going through chemotherapy. Just the recognition that chemobrain is real relieves the frustration of yet another area of their lives where they feel out of control.

Dr. O’Shaughnessy has submitted the results of her study on Procrit for the 38th Annual Meeting of the American Society of Clinical Oncology (ASCO). She hopes to begin a larger study on the role of Procrit in cognitive dysfunction later this year. Dr. Loprinzi says that his results on Ginkgo biloba will not be known for two years.

The good news is that chemobrain seems to get better with time. I can remember all my grandchildren’s names and find my car keys for a weekly trip to the grocery store. And the things I do forget‚ I can gratefully blame on aging.