New prospective magnetic resonance imaging (MRI) research demonstrates elevated neurotoxicity risks in patients with cardiac dysfunction related to neoadjuvant chemotherapy (NAC) for invasive breast cancer (BC).
For the study, recently published in Academic Radiology, researchers reviewed heart and brain MRI parameters prior to and after the use of six to eight rounds of NAC for 85 patients with invasive breast cancer. The cohort was comprised of 18 patients with cancer therapy-related cardiac dysfunction (CTRCD) and 67 patients with cardiac dysfunction unrelated to NAC, according to the study.
After NAC treatment, the researchers found that patients with CTRCD had significantly greater median changes in:
• left ventricular ejection fraction (LVEF) (-12.231 vs. -1.076);
• left ventricular end-systolic volume (LVESV) (3.1 vs. 0.350); and
• left ventricular stroke volume (LVSV) (-18.310 vs. -2.818).
Employing a composite cardiotoxicity factor (FAC) to represent cardiac dysfunction severity, the study authors pointed out that worse FAC in the CTRCD cohort was associated with significantly greater median changes in total brain volume (TBV) (-0.792), gray matter volume (GMV) (-0.752) and white matter volume (WMV) (-0.773).
“In BC patients with CTRCD, a notable correlation exists between the FAC and changes in brain structure. These findings suggest that cardiotoxicity and related neurotoxicity can occur simultaneously, particularly in BC patients with CTRCD,” noted lead study author Xunrong Luo, MS, who is affiliated with the Department of Radiology at Chongqing University Cancer Hospital and the School of Medicine at Chongqing University in Chongqing, China, and colleagues.
Three Key Takeaways
• CTRCD signals higher neurotoxicity risk. Breast cancer patients who develop cancer therapy–related cardiac dysfunction (CTRCD) after neoadjuvant chemotherapy show significantly greater declines in cardiac function (e.g., LVEF, LVSV) and concurrent reductions in brain volumes, suggesting a linked heart–brain toxicity pathway.
• Cardiac dysfunction severity correlates with brain atrophy. A higher composite cardiotoxicity score (FAC) was associated with greater loss of total brain volume, gray matter, and white matter, supporting a possible dose-response relationship between cardiotoxicity and neurostructural changes.
• MRI detects parallel cardiac and cerebral changes post-NAC. Prospective imaging demonstrated that measurable deterioration in cardiac parameters after NAC occurs alongside quantifiable reductions in brain structure on MRI, reinforcing the value of combined heart–brain imaging to identify patients at higher risk for treatment-related toxicity.
The researchers noted that their study findings parallel previous research demonstrating correlations between reduced LVEF and decreased TBV and WMV in this patient population.
“Based on this, we propose that cancer cell-derived endotoxins remodel the tumor microenvironment, leading to systemic inflammation, which in turn drives cardiac dysfunction. This cardiac dysfunction may result in cerebral hypoperfusion, which may induce hemodynamic instability that ultimately manifests as structural brain damage and atrophy. Taken together, these findings suggest that some BC patients may have insufficient cardiac reserve before treatment, which can affect brain perfusion,” posited Luo and colleagues.
(Editor’s note: For related content, see “Post-NAC Breast MRI Without Calcifications Associated with 65 Percent Higher Likelihood of Pathologic Complete Response,” “New Research Assesses the Impact of Pre-Op MRI on Breast Cancer Recurrence” and “Multimodal AI Model with mpMRI Radiomics Improves Long-Term Post-NAC Survival Prediction.”)
In regard to study limitations, the authors acknowledged the small cohort of patients with CTRCD (18), the single-center design and the lack of external validation. The researchers also conceded that possible impacts of myocardial fibrosis and atrial fibrillation upon brain MRI findings were not evaluated.
