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The following is a summary of “Interaction between APOE Ɛ4 status, chemotherapy and endocrine therapy on cognitive functioning among breast cancer survivors: the CANTO-Cog longitudinal study,” published in the February 2025 issue of the Breast Cancer Research by Duivon et al.

The presence of the Apolipoprotein E ε4 (APOE4) genotype has been associated with an increased risk of cancer-related cognitive impairment; however, its interaction with specific breast cancer treatments remains uncertain. This longitudinal study investigates the relationship between APOE4 and cognitive function in women undergoing chemotherapy and/or endocrine therapy for breast cancer, aiming to determine whether APOE4 status influences cognitive decline over time.

A total of 334 women diagnosed with stage I–III breast cancer underwent cognitive assessments at four-time points: baseline (at diagnosis, prior to surgery), and at one, two, and four years post-diagnosis. APOE4 status was determined through blood sample genotyping, categorizing participants as either APOE4 carriers (APOE4+) or non-carriers (APOE4−). The cognitive domains evaluated included episodic memory, working memory, attention, processing speed, and executive function. Overall cognitive impairment was defined as impairment in at least two cognitive domains. Logistic and linear mixed models were utilized to assess the associations between APOE4 status and cognitive impairment over time, as well as potential interactions between APOE4 and CT or ET.

Among the 334 participants, 64 (19%) were APOE4 carriers. Treatment distribution included 117 (35%) patients receiving CT alone, 41 (12%) receiving ET alone, and 162 (49%) receiving a combination of CT and ET. The analysis revealed no significant association between APOE4 status and overall cognitive impairment, nor any significant interactions between APOE4 and CT or ET in relation to global cognitive function. However, at the four-year follow-up, patients with APOE4+ who received ET exhibited significantly lower attention performance compared to patients with APOE4− who did not receive ET. Additionally, patients with APOE4+ who were not treated with ET demonstrated lower episodic memory performance than their APOE4− counterparts who were also not treated with ET. These findings suggest that while APOE4 alone does not strongly predict overall cognitive impairment in patients with breast cancer, specific cognitive domains may be affected depending on ET exposure and APOE4 status.

In conclusion, APOE4 genotyping does not appear to be a reliable predictor of treatment-related cognitive impairment in women with breast cancer. These findings highlight the need for further research to identify alternative genetic or biological markers that may better predict cognitive decline associated with cancer therapies. Understanding these risk factors could help develop targeted interventions to mitigate cognitive dysfunction in patients with breast cancer receiving CT and ET.

Source: breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-025-01974-2