A significant percentage of patients with non-metastatic breast cancer and post-chemotherapy cognitive decline has signs of dysfunction before treatment, according to an article published online June 21st by the journal Cancer. The series of studies are the first to document pre-treatment dysfunction (mainly in learning and memory) in this population.

"These losses are not due to emotions or anxiety, and patients are grateful when it is recognized," said Christina Meyers, PhD, senior author. "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 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," said Jeffrey Wefel, PhD, the study’s lead author. "Most cancer treatments also will cause a decline in cognition in a vulnerable subset of patients."

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

The current study looked specifically at cognitive decline before treatment in three cohorts (total, 84 patients) treated at the same specialized cancer center. Across the three samples, 35 percent (29 patients) exhibited impairments in verbal learning and memory functions compared with normals for these patients.

Although they do not know why the declines occurred, the authors 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," said Meyers.

She said causes of cognitive decline in cancer development could be due to host-related factors, disease-related factors, or both. Host-related factors include genetic differences, immune reactivity, nutritional factors, and hormonal status. Disease-related factors include tumor gene mutations and an inflammatory or autoimmune reaction provoked by the cancer.