Connectome analysis of brain functional network alterations in breast cancer survivors with and without chemotherapy

Treatment modalities for breast cancer, the leading cause of cancer-related deaths in women worldwide, include surgery, radiotherapy, adjuvant chemotherapy, targeted therapy, and hormonal therapy. The advancement in medical technology has facilitated substantial reduction in breast cancer mortality. However, patients may experience cognitive impairment after chemotherapy. This phenomenon called chemotherapy-induced cognitive impairment (i.e., "chemobrain") is common among breast cancer survivors. However, cognitive function deficits may exist before chemotherapy initiation. This study examined the functional network alterations in breast survivors by using resting-state functional magnetic resonance imaging (fMRI).

We recruited 172 female participants and separated them into three groups: C+ (57 breast cancer survivors who had finished 3-12-month-long chemotherapy), C- (45 breast cancer survivors who had not undergone chemotherapy), and HC (70 participants with no breast cancer history). We analyzed mean fractional amplitudes of low-frequency fluctuation and graph theoretical topologies from resting-state fMRI and applied network-based analysis to portray functional changes among the three groups.

Among the three groups, the C- group demonstrated hyperactivity in the prefrontal cortex, bilateral middle temporal gyrus, right inferior temporal gyrus and right angular gyrus. Only the left caudate demonstrated significantly more hypoactivity in the C- group than in the C+ group. Graph theoretical analysis demonstrated that the brains of the C+ group became inclined toward regular networks and the brains of the C- group became inclined toward random networks.

Subtle alterations were noted in the brain activity and networks of our cancer survivors. Moreover, functional network disruptions occurred regardless of chemotherapeutic agent administration.