Chemotherapy May Not Cause Cognitive Problems in Breast Cancer Patients

Susan Jeffrey

April 15, 2008

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April 15, 2008 (Chicago, Illinois) — Although women treated for breast cancer frequently report cognitive problems during chemotherapy, 2 new studies suggest that the chemotherapy itself may not be the cause of these problems.

In separate reports, researchers find that cognitive changes are detectable before chemotherapy is undertaken, suggesting that the stress of the diagnosis may have an impact on cognition in these women.

The findings may offer some reassurance that although the problem is real, it does not happen in all patients and that it is "mild and measurable," said David G. Darby, MD, chief medical officer of CogState Ltd, an Australian company that developed the cognitive battery used in both of these studies. Only about 10% had persistent problems, some slowing of processing comparable to being jetlagged, he said.

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In a separate report, Michael J. Boivin, MD, from Michigan State University, showed that, compared with newly diagnosed breast cancer patients and those who underwent biopsy but had a benign diagnosis, breast cancer survivors assessed about 1 year after their last chemotherapy treatments were actually more accurate in working memory and learning performance than women in these other groups.

Both papers were presented here at the American Academy of Neurology 60th Annual Meeting.

"Chemobrain"

About 200,000 women in the United States receive a new diagnosis of breast cancer each year, but treatment has improved such that 5-year survival is now estimated at about 90%, Dr. Darby said. "As survival improves, quality-of-life [QoL] issues take on a greater importance," he said. "When making decisions about treatment, women need to be fully informed about its effects."

Cognitive deficits associated with chemotherapy, sometimes called "chemobrain" or "chemofog," have been reported anecdotally but have been difficult to study. Ideally, women should be assessed before their diagnosis, but this is not generally possible, he said. As a compromise, Dr. Darby and colleagues tested women after diagnosis but before chemotherapy and then after treatment.

Thirty women with breast cancer underwent cognitive assessment before each cycle of chemotherapy and then again at 28 days after the final cycle. Subjective cognitive function, depression, and anxiety measures were also taken at each assessment. As controls, they also tested 30 healthy age-matched women who underwent assessment on 6 occasions about 1 month apart.

The authors report that even before they underwent chemotherapy, cognitive performance in the women with breast cancer was significantly impaired vs controls on assessments of monitoring (P <  .001; effect size, -0.8) and learning (P = .02; effect size, -0.57).

After the final cycle of chemotherapy, group analyses showed that performance had declined significantly on only 1 parameter, the speed of detection (P = .008; effect size, -0.35)

Individual analyses showed that 3 women, or 10% of the original group, did have persistent cognitive impairment, defined as deficits present on 2 consecutive assessments, Dr. Darby noted.

Interestingly, at a group level, depression and anxiety levels did not significantly correlate with objective performance on these tests, although subjective cognitive impairment did. However, at an individual level, those who reported cognitive problems were not reliably the ones who had them by objective testing.

"Prior to chemotherapy, women with breast cancer show subtle but reliable impairment in attention and learning," Dr. Darby concluded. "Chemotherapy treatment is associated with only a minor slowing in psychomotor function."

These women were treated with 2 regimens of chemotherapy, including some who received 5-fluorouracil, which has been thought to be neurotoxic, he noted. In this assessment, however, this regimen was actually found to be more benign from a cognitive standpoint.

Quality of Life Key?

In their report, Dr. Boivin and colleagues correlated QoL measures and cognitive performance in 3 groups of women participating in the Spirituality, Emotional Well Being, and Quality of Life (SEQL) project, an ongoing study examining the cognitive, social, and emotional impact of breast cancer diagnosis and treatment.

Subjects included 44 breast cancer patients prior to any chemotherapy or radiation therapy, 30 women who had had a biopsy that was ultimately found to be benign, and 20 breast cancer survivors, women who had completed breast cancer treatment at least 1 year previous to testing.

At 4-month follow-up, 28 of 44 breast cancer patients and 10 of the 30 patients with a benign biopsy were available for assessment.

All subjects were assessed using the CogState cognitive evaluation and the HOPE Breast Cancer Quality of Life Scale, with questions related to physical, psychological, emotional (distress and fear), social, and spiritual well-being.

They found significant between-group differences in accuracy of assessments of working memory and associative learning, with the breast cancer survivors performing better than both the patients with a breast cancer diagnosis who had not yet received treatment and the women who had had a benign biopsy.

Significant between-group differences were also seen on psychological QoL, with survivors scoring significantly better than both the breast cancer and benign-biopsy groups. Gains in spiritual QoL scores from diagnosis to 4 months for women in the breast cancer and biopsy groups correlated with gains in continuous paired-associate learning and associative learning, they note. Gains in psychological QoL between diagnosis and 4 months correlated with gains in attention/vigilance accuracy and speed.

These results suggest that there is a "much tighter coupling between quality of life — emotional, spiritual, social, psychological well-being in particular — and cognitive ability and performance, and perhaps these aspects of quality of life provide an important buffer in terms of the possible deleterious effects of breast cancer treatment, particularly chemotherapy."

"In fact," Dr. Boivin added, "the hopeful message we believe is that perhaps with the right types of support, the effects of chemotherapy can be buffered, and if after treatment they draw on the resources that are available to them — psychosocial support, physical activity, fellowship enjoyed with other survivors — that they can make full recovery, perhaps even thrive in terms of cognitive performance."

For clinicians who care for these patients, this means informing women about the importance and prognostic value of maintaining quality of life should be part of a treatment plan for breast cancer in both the short and long term, he concluded

In future analyses, they plan to look at the relationships between cognitive performance, emotional and spiritual well-being, and immunological recovery examined before and after treatment and after 1 year. They also plan functional magnetic resonance imaging activation studies looking at the response to spiritual and emotional pictures, again before and after treatment.

The study by Dr. Darby and colleagues was supported by CogState Ltd, the University of Melbourne, and the Peter MacCallum Cancer Center. Dr. Darby reports that he received salary support from CogState Ltd and holds stock and stock options in CogState Ltd. He also has received research support from Pfizer Australia. Disclosures for other coauthors appear in the abstract. The study by Dr. Boivin and colleagues was supported by Templeton Advance Research Program. The authors have nothing to disclose.

American Academy of Neurology 60th Annual Meeting: Abstract S06.004, P03.134. Presented April 15, 2008.

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