UCLA

Cognitive impairment during and after treatments for breast cancer, referred to as cancer-related cognitive impairment (CRCI), is one of the most common and troublesome consequences of the cancer experience. Women report experiencing difficulties with memory, multi-tasking, and keeping up with the demands of what used to be cognitively manageable tasks. Over the last several decades, both pre-clinical and clinical research have provided empirical evidence supporting an association between the cancer experience and cognitive problems; however, several gaps in the literature remain. First, the study of CRCI has primarily focused on the influence of adjuvant therapies given that women often complain of cognitive disturbances following chemotherapy, referring to the experience as “chemo-brain.” However, longitudinal investigations into the onset and maintenance of CRCI have identified pre-chemotherapy cognitive impairment that cannot be explained by presumed cytotoxic effects. These pre-systemic therapy cognitive problems could potentially be driven by breast cancer surgery, the primary treatment for solid tumor cancers. Although breast cancer surgery is included in almost every conceptual model of CRCI, few studies have examined the association between different surgery types and cognitive problems over time. Second, the prevailing biological mechanistic theory linking the cancer experience with cognitive problems is increases in peripheral inflammation resulting in neuroinflammation. However, a paucity of studies have examined associations between inflammation and CRCI, even fewer have investigated this relationship longitudinally, and only one study to our knowledge that has interrogated within-subject associations. Third, most studies have examined mean levels of cognitive problems over time, which masks heterogeneity. Therefore, investigations into distinct group-based trajectories of cognitive problems over time in breast cancer survivorship are required. This approach will also enable the identification of various clinical, psychological, and biological risk factors for elevated cognitive problems throughout survivorship. Thus, this dissertation comprises three different studies of breast cancer-related cognitive impairment. Study 1, “Surgery-Chemo-Brain?” The role of surgery in cancer-related cognitive impairment in breast cancer survivors,” assessed the associations between different surgery types and perceived and objective cognitive problems over time. Study 2, “The role of peripheral inflammation in cancer-related cognitive problems,” assessed between- and within-subjects associations between inflammation and perceived and objective cognitive problems longitudinally. Study 3 “Trajectories of perceived and objective breast cancer-related cognitive problems,” characterized group-based trajectories of perceived cognitive problems as well as identified clinical, psychological, and biological risk factors for group membership. We used rich biobehavioral data from one or both of two longitudinal observational cohort studies of breast cancer survivors, the RISE and Mind-Body Studies, to conduct these studies. Together, these studies further our understanding of clinical drivers of, biological mechanisms of, and risk factors for trajectories of CRCI.