Cognitive decline can occur before chemotherapy treatment

In a series of studies in breast cancer patients, researchers at The University of Texas M. D. Anderson Cancer Center have confirmed the presence of “chemobrain” after chemotherapy treatment – but they also discovered that a significant portion of patients have cognitive declines even before chemotherapy.

The studies, the latest of which is reported June 21 in the online edition of the journal Cancer, are the first to document such pretreatment losses in patients with non-metastatic breast cancer. Researchers suggest that problems associated mostly with learning and memory likely arise due to the disease process itself, lending validation to patients who have noticed the problems, but have a hard time convincing their physicians.

“These losses are not due to emotions or anxiety, and patients are grateful when it is recognized,” says Christina Meyers, Ph.D., professor of neuropsychology in the Department of Neuro-Oncology, who has lead the series of studies. “We want them to know that we are trying to understand why this happens and that there are a wide variety of therapies available to help them.”

The research team cannot yet pinpoint a reason as to why the declines occur, but say factors such as a systemic immune inflammatory reaction produced during illness may play a role, as may a person’s hormonal profile and unique genetic susceptibilities.

They add that the problem is likely not related to gender: Meyers has also found similar cognitive declines before chemotherapy treatment in men with non-small cell lung cancer.

“There is a subset of patients with any kind of cancer who may have cognitive impairment related to having the cancer, and there may be a number of different biological reasons as to why this happens,” says first author Jeffrey Wefel, Ph.D., a member of Meyers’ neuropsychology group. “Most cancer treatments also will cause a decline in cognition in a vulnerable subset of patients.”

All studies of “chemobrain” – cognitive decline due to chemotherapy – have measured brain functioning only after treatment. In this series of studies, the researchers looked at data from three separate prospective clinical trials conducted at M. D. Anderson that examined cognitive functioning before patients with non-metastatic breast cancer were treated with either tamoxifen or chemotherapy. In each investigation, patients received a comprehensive neuropsychologic evaluation before treatment.

The first report, published in Cancer June 1, looked at one of the groups, composed of 18 patients who were to receive chemotherapy. The researchers found that before treatment, 33 percent of these patients showed cognitive impairments when tested, based on the expected scores they should have received given their ages, education, employment history and associated variables. After treatment with chemotherapy, 61 percent of this group demonstrated “chemobrain” declines in memory and learning.

Not every woman with early declines showed further declines after treatment, Meyers noted. “If they had a problem before chemotherapy, treatment did not necessarily provide an additional risk to declining further,” she says.

One year after treatment, 50 percent of patients with “chemobrain” improved, the researchers found.

Studies on the other two cohort groups, one of which is near submission, showed similar results, Meyers says.

The study just reported in Cancer looked specifically at cognitive decline before treatment in all three cohorts, which totaled 84 patients. It found that, over all the groups, 35 percent (29 patients) exhibited impairments in verbal learning and memory functions compared to what was considered normal for these patients.

Although they do not know why the declines occurred, they noted “several provocative trends.” Patients who appeared to have a greater risk of impairment either underwent more invasive surgery (lumpectomy or mastectomy), were postmenopausal, or had not previously used hormone replacement therapy. “Hormonal status may reduce a cognitive reserve, which may be associated with greater risk for suffering from adverse symptoms but we really don’t know,” says Meyers.

She says causes of cognitive decline in cancer development could be due to the “soil” – host-related factors – or the “seed” – disease-related factors, or an interplay between both. Soil can include genetic differences, immune reactivity, nutritional factors, and hormonal status. Seed factors include tumor gene mutations, and an inflammatory or autoimmune reaction provoked by the cancer.

The researchers are continuing to investigate the roots of cognitive decline unrelated to treatment. Wefel says that if additional studies continue to show an association between cancer processes and mental functioning, patients may best be served by having cognitive tests as soon as cancer is diagnosed, as well as after treatment. “We have a whole platter of treatments to choose from that can help patients,” Meyers says, which ranges from medications to accepted alternative therapies.

The study was supported in part by a dissertation research grant from the Susan G. Komen Foundation. Co-authors include Renato Lenzi, M.D., Richard Theriault, D.O., Aman Buzdar, M.D. of M. D. Anderson and Scott Cruickshank, M.A.