Chemotherapy and The Brain: Breast Cancer Treatment Alters Brain Networks

A study followed women with breast cancer and showed that chemotherapy causes changes in brain connections, affecting areas linked to emotions and cognition. These changes appear early in treatment and become even stronger over time, which helps to explain the difficulties with memory, attention and reasoning that many patients face. The research reinforces the importance of taking care of mental health during and after cancer treatment.

Treatment of breast cancer with chemotherapy is essential to combat the disease, but it can have side effects that go beyond the body, also affecting brain function. One of these effects is the so-called "cancer-related cognitive impairment" (CRCI), a condition that can impair memory, attention and the ability to think clearly.

Understanding how these changes in the brain develop over the course of treatment is essential to improving the quality of life of these patients.

This study aimed to observe how chemotherapy changes brain connections over time in women with breast cancer.

The study followed 55 women diagnosed with breast cancer who had undergone chemotherapy before surgery (a treatment called neoadjuvant chemotherapy, or NAC). Participants underwent functional magnetic resonance imaging (fMRI) scans and clinical evaluations at three time points:

1. Before starting chemotherapy (TP1)

   
   

2. After the first cycle of treatment (TP2, about 30 days later)

   
   

3. At the end of chemotherapy (TP3, about 140 days later).

In addition, two groups of healthy women of similar ages also underwent the same tests, so that results could be compared.

Connectomes

The imaging tests used allowed them to observe how different regions of the brain communicate with each other, forming networks of connections, known as connectomes.

Using tools from graph theory (a way of mapping networks and understanding their organization), the researchers analyzed changes in these brain networks over time. In addition, they related these changes to emotional and cognitive performance tests performed by the participants.

The results showed that, soon after the start of chemotherapy, the patients' brains began to show signs of reorganization: there was an increase in the overall efficiency of the brain's communication networks and a decrease in the "path" that information needs to travel to be transmitted between brain regions, changes that were especially visible in areas associated with emotions and motor control (such as the fronto-limbic system and the cerebellar cortex).

These changes not only persisted until the end of treatment, but also intensified. The changes in the connectomes also correlated with the worsening of emotional and cognitive symptoms reported by the patients.

It is important to note that these changes did not occur in the groups of healthy women, and at the beginning of the study, before chemotherapy, there were no differences between the brains of the patients and the healthy women. This indicates that the observed changes actually emerged during treatment.

In summary, the study shows that neoadjuvant chemotherapy causes significant changes in the brain connections of breast cancer patients, changes that continue to evolve throughout treatment and are associated with the cognitive difficulties that many of these women face.

These findings help to better understand the effects of chemotherapy on the brain and reinforce the importance of seeking strategies to protect mental health during and after treatment.

READ MORE:

Altered Brain Functional Networks in Patients With Breast Cancer After Different Cycles of Neoadjuvant Chemotherapy

Jing Yang, Yongchun Deng, Daihong Liu, Yixin Hu, Yu Tang, Xiaoyu Zhou, Yong Tan, Jing Zhang, Jiang Liu, Chengfang Wang, Xiaohua Zeng, Jiuquan Zhang

Journal of Magnetic Resonance Imaging. First published: 09 April 2025 

https://doi.org/10.1002/jmri.29772

Abstract:

Cancer-related cognitive impairment (CRCI) impacts breast cancer (BC) patients' quality of life after chemotherapy. While recent studies have explored its neural correlates, single time-point designs cannot capture how these changes evolve over time. To investigate changes in the brain connectome of BC patients at several time points during neoadjuvant chemotherapy (NAC). 55 participants with BC underwent clinical assessments and fMRI at baseline (TP1), the first cycle of NAC (TP2, 30 days later), and the end (TP3, 140 days later). Two matched female healthy control (HCs, n = 20 and n = 18) groups received the same assessments. rs-fMRI (gradient-echo EPI) and 3D T1-weighted magnetization-prepared rapid gradient echo sequence at 3.0 T. Brain functional networks were analyzed using graph theory approaches. We analyzed changes in brain connectome metrics and explored the relationship between these changes and clinical scales (including emotion and cognitive test). Patients were divided into subgroups according to clinical classification, chemotherapy regimen, and menopausal status. Longitudinal analysis was performed at three time points for each subgroup. An independent sample t-test for patient-HC comparison at TP1. Analysis of variance and paired t-test for longitudinal changes. Regression analysis for relations between network measurements changes and clinical symptom scores changes. Significance was defined as p < 0.05. Post-NAC, BC patients showed increased global efficiency (TP2-TP1 = 0.087, TP3-TP1 = 0.078), decreased characteristic path length (TP2-TP1 = −0.413, TP3-TP1 = −0.312), and altered nodal centralities mainly in the frontal-limbic system and cerebellar cortex. These abnormalities expanded with chemotherapy progression significantly (TP2 vs. TP3). Topological parameters changes were also correlated with clinical scales changes significantly. No differences were found within or between HC groups (p = 0.490–0.989) or BC subgroups (p = 0.053–0.988) at TP1. NAC affects the brain functional connectome of BC patients at TP2, and these changes persist and further intensify at TP3.