4396

Altered topological organization and functional brain connectome in breast cancer patients with fear of cancer recurrence

Tianye Lin¹, Yihe Zhang², Yening Zhang³, Yang Yang³, Lili Tang³, and Yingshi Sun³
¹Radiology, Peking University Cancer Hospital & Institute, Beijing, China, ²Beijing University of Posts and Telecommunications, Beijing, China, ³Peking University Cancer Hospital & Institute, Beijing, China

Synopsis

Keywords: Functional Connectivity, fMRI (resting state)

Motivation: Fear of cancer recurrence (FCR) is a common psychological condition in breast cancer patients.

Goal(s): To reveal the FCR neural mechanism on the whole-brain connectome network level.

Approach: We collected resting-state functional MRI from 43 breast cancer patients and 40 healthy controls (HCs).

Results: Graph theory analyses revealed a decreased clustering coefficient in breast cancer patients compared to healthy control subjects. Breast cancer patients showed lower FCS in hub regions of DMN and higher FCS in frontoparietal, DMN, dorsal attention and primary somatomotor networks. Among the hyperconnected regions, the left inferior frontal operculum (IFO) showed a significant positive correlation with FCRI-severity.

Impact: Our study indicated that breast cancer patients have a more random-like functional network. FCS in some specific brain regions of breast cancer patients such as left IFO was associated with FCR severity.

Background

Breast cancer surpassed lung cancer to become the most commonly diagnosed cancer worldwide in 2020[1]. The survival rate and life span of breast cancer patients also extended. Consequently, in the management of breast cancer, the aim is to preserve quality of life with prolonged life expectancy. Fear of cancer recurrence (FCR), defined as ‘the fear or worry that the cancer will return or progress in the same organ or in another part of the body’ [2, 3], is a common emotional disturbance in breast cancer patients and has negative effects on patients’ quality of life[4]. Using rs-fMRI, many studies have shown altered brain network topology[5] and network functional connectivity[6] in chemotherapy-treated breast cancer patients. To date, only two studies using rs-fMRI assessed the association of FCR and neural disruption in patients with cancer[7] [8]. They focused on regional spontaneous brain activity(i.e. amplitude of low-frequency fluctuations (ALFF), regional homogeneity(ReHo) and voxel-mirrored homotopic connectivity (VMHC)). However, we still lack evidence of FCR neural mechanism on the whole-brain connectome network level. In this study, we employed rs-fMRI seed-based voxel-wise functional connectivity analysis and graph theory analysis to compare the brain connectome and topological organization in non-metastatic breast cancer patients and healthy control subjects. Furthermore, we also explored the relationships between the brain network indicators and FCR in breast cancer patients.

Methods

We collected resting-state functional MRI on a 3.0T uMRI 790 scanner using a 32 channels head coil from 43 breast cancer patients and 40 healthy controls (HCs). The rs-fMRI data were obtained by a gradient-echo planar imaging sequence, repetition time (TR)= 700 ms, echo time (TE) = 30 ms, flip Angle (FA) = 52°, field of view (FOV) = 210x210 mm, voxel size = 2.5x2.5x2.5mm, matrix = 84x84, multi-layer excitation acceleration: 7 times, scan time: 8min22s. FCR was evaluated for all patients using a self-report scale FCRI and a shorter form subscale FCRI-severity[9, 10]. A higher score indicates higher levels of FCR. We calculated global network metrics include small world property, gamma, lambda, clustering coefficient and characteristic path length and their relationship with FCR. We conducted whole-brain voxel-wise functional connectivity strength (FCS) analysis followed by seed-based functional connectivity (FC) analysis. Non-parametric permutation statistical tests were utilized to identify brain regions with altered connectivity in breast cancer patients. We also calculated the correlation between brain functions (i.e., FCS and FC) and FCR scores (i.e., FCRI and FCRI-severity).

Results

Graph theory analyses revealed a decreased clustering coefficient in breast cancer patients compared to healthy control subjects (Figure 1, P=0.04), but no global network metrics were associated with FCR. Breast cancer patients showed lower FCS regions in right inferior frontal orbital, right superior frontal gyrus, right cuneus and precuneus, right angular, left inferior parietal, left rectus and left calcarine, many of these are hub regions of DMN (Figure 2). Breast cancer patients showed higher FCS in both high-order function (frontoparietal, default mode and dorsal attention systems) and primary somatomotor networks (Figure 2). The FCRI and FCRI-severity related FCS clusters in breast cancer patients had similar spatial distributions (Figure 3, Figure 4). Among the hyperconnected regions in breast cancer, the left inferior frontal operculum (IFO) showed a significant positive correlation with FCRI-severity.

Conclusions and discussion

Our study indicated that breast cancer patients have a more random-like functional network. FCS in some specific brain regions of breast cancer patients such as left IFO was associated with FCR severity. The IFO has been implicated in various aspects of emotion processing. A meta-analysis study showed that the IFO and the anterior insula were activated by both pain-related and non-pain related fear [11]. Moreover, panic disorder patients showed prolonged fear activation in the left IFO and right insula during fear extinction recall compared to healthy controls [12]. These findings provided insights into neural mechanism of FCR in breast cancer patients on brain connectome level.

Acknowledgements

No acknowledgement found.

References

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[7] Zhou J, Feng P, Lu X, Han X, Yang Y, Song J, et al. Do Future Limitation Perspective in Cancer Patients Predict Fear of Cancer Recurrence, Mental Distress, and the Ventromedial Prefrontal Cortex Activity? Front Psychol. 2018;9:420.

[8] Peng L, Hu X, Xu C, Xu Y, Lai H, Yang Y, et al. Altered regional homogeneity and homotopic connectivity in Chinese breast cancer survivors with fear of cancer recurrence: A resting-state fMRI study. J Psychosom Res. 2023;173:111454.

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[11] Biggs EE, Timmers I, Meulders A, Vlaeyen JWS, Goebel R, Kaas AL. The neural correlates of pain-related fear: A meta-analysis comparing fear conditioning studies using painful and non-painful stimuli. Neurosci Biobehav Rev. 2020;119:52-65.

[12] Schwarzmeier H, Kleint NI, Wittchen HU, Strohle A, Hamm AO, Lueken U. Characterizing the nature of emotional-associative learning deficits in panic disorder: An fMRI study on fear conditioning, extinction training and recall. Eur Neuropsychopharmacol. 2019;29:306-18

Figures

Figure 1. Group difference of global network metrics. Values for each metric were scaled to range 0 to 1. Significant group difference feature was marked with *, P values were not corrected for multiple comparison. BC, breast cancer group. HC, healthy control group. Among all global network metrics, breast cancer subjects showed lower clustering coefficient than healthy control subjects (P=0.04).

Figure 2. Significantly altered FCS clusters in brains with breast cancer. BC, breast cancer group. HC, healthy control group. Significance P values for all FCS clusters were <0.001 after FDR correction.

Figure 3. Significant correlated FCS clusters with FCRI-severity score. Each dot represents a subject, dashed lines indicate the confidence interval of the regression. Significance levels of correlation results were Bonferroni corrected for multiple comparisons.

Figure 4. Significant correlated FCS clusters with FCRI score. Each dot represents a subject, dashed lines indicate the confidence interval of the regression. Significance levels of correlation results were corrected for multiple comparisons by standard of False Discovery Rate.

Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)

4396

DOI: https://doi.org/10.58530/2024/4396