What happens next? The Long-Term Impact of Cancer Treatment on Memory and Affective Symptoms in Breast Cancer Survivors

Abstract

Breast cancer is the most frequently diagnosed cancer worldwide, with increasing survival rates heightening awareness of long-term treatment-related effects on cognitive and mental health. Memory impairments are among the most commonly reported and functionally impactful complaints in survivors. However, most memory research relies on laboratory-based tasks that may not capture the complexity of everyday episodic memory, which depends on hippocampal mechanisms supporting the encoding and retrieval of rich contextual information and may be vulnerable to chemotherapy-related neurotoxicity. This thesis examines the long-term impact of breast cancer treatment on cognitive and psychological functioning across four objectives: (1) reviewing mechanisms underlying episodic memory impairment following cancer treatment, (2) characterizing long-term psychological outcomes and their interrelationships, (3) assessing episodic memory using standard and ecologically valid measures over short delays, and (4) evaluating memory for complex naturalistic events using film-based stimuli over extended delays, focusing on central and peripheral details.

We recruited Canadian women aged 30-65 years with a history of breast cancer who were at least six months post-treatment and age-matched non-cancer controls. During the first session, participants provided demographic and health information, and completed online questionnaires assessing stress, depression, anxiety, fatigue, and sleep quality. In the second session, participants completed two cognitive tasks to assess episodic memory using a narrative recall and verbal paired associates task, and two questionnaires to assess cognitive workload and perceived episodic and semantic memory abilities. In the final two sessions, participants viewed 40 short film clips and were asked to recall 20 clips immediately after encoding and the remaining 20 after a 7-day delay.

Breast cancer survivors reported higher levels of stress, depression, anxiety, fatigue, and sleep disturbance than controls, with each factor being interrelated. Breast cancer survivors recalled fewer verbatim and gist details for the narrative recall task than non-cancer controls, with impairments in gist memory persisting during delayed recall. However, no memory deficits were evident on the paired associate task in breast cancer survivors. Breast cancer survivors reported greater cognitive effort during the story recall tasks, but no group differences emerged for the paired associate task. Survivors also reported greater cognitive effort during narrative tasks and greater subjective memory difficulties. In the film-based task, both groups showed comparable rates of forgetting over time; however, survivors recalled fewer central and peripheral details overall, with specific impairments for object-related and multimodal (spatial, auditory, and event-based) information.

The findings highlight the enduring cognitive and psychological sequelae of cancer treatment in breast cancer survivors, which may be partly influenced by the neurotoxic effects of chemotherapy on hippocampal functioning, a brain region critically involved in episodic memory. Although survivors performed similarly to non-cancer controls on standard neuropsychological memory measures, they demonstrated impairments on more complex, ecologically valid memory tasks, suggesting that traditional assessments may underestimate the everyday memory challenges experienced in survivorship. Furthermore, survivors exhibited difficulties recalling both gist-based and episodically rich details of naturalistic events, providing evidence of specific episodic memory vulnerabilities following treatment. Together, these findings support the need for comprehensive survivorship assessments incorporating ecologically valid cognitive measures alongside standard tests and subjective reports to better identify functional impairments and guide intervention strategies.