Researchers have begun to question whether or not these cognitive changes are a result of chemotherapy, or develop because of the cancer itself. Although primary breast cancer has not been historically associated with neurological problems, a growing body of evidence suggests that women with primary breast cancer may be at high risk for altered brain structure and function. These neurobiologic abnormalities may be associated with neurocognitive deficits, but their specific causes remain unclear.12,13

Abnormal brain structure and function have been associated with chemotherapy, but similar changes have been demonstrated prior to patients receiving adjuvant chemotherapy, suggesting a complex mix of risk factors.12,14,15 A  2011 article by Kesler and colleagues evaluated prefrontal cortex and executive functioning in women with primary breast cancer.16 It was found that the women in the study with breast cancer — those that had not received chemotherapy (n=19), and those that received chemotherapy (n=25) — demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls (n=18). In addition, women with primary breast cancer that received chemotherapy demonstrated significantly reduced left caudal lateral prefrontal cortex activation, increased perseverative errors, and reduced processing speed compared with the other two groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. These findings suggest neurologic impairment associated with primary breast cancer, regardless of whether the patient has received treatment.

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In a recently published clinical trial, Phillips and colleagues reported that cognitive deficits are present in women with breast cancer who received radiotherapy.17 Women with Stage 0–2 breast cancer treated with chemotherapy plus radiotherapy (n=62) or radiotherapy alone (n=67) completed neurological assessments at six months after completing therapy and 36 months following that. Women with no history of breast cancer (n=184) served as the control group and were evaluated at similar intervals. Cognitive performances were assessed with a battery of tests that evaluated overall intellectual ability, attention, executive functioning, nonverbal memory, processing speed, and verbal memory. Women receiving chemotherapy plus radiotherapy, and those women receiving radiotherapy alone, did poorly on cognitive-performance tests that evaluated processing speed and executive functioning at six months and three years post treatment compared to those women that did not have breast cancer. An additional analysis found that hormonal therapy did not affect cognitive performance over time. The results from this trial suggest that the memory loss normally associated with chemotherapy may also be associated with radiotherapy, and healthcare providers should discuss these effects with their patients, as well.