Current Research


Chemotherapy-related cognitive impairment (CRCI) affects an estimated 60% of patients, negatively impacting quality of life. Currently, there is no established method for predicting which patients will develop CRCI.

This information could be practice-changing by assisting clinicians with treatment decision-making for individual patients. We have shown that the brain network (“connectome”) is significantly altered in patients with CRCI. Therefore, we measured the connectome is patients prior to any treatment and demonstrated that these connectome properties could be used in combination with machine learning to predict 1 year post-chemotherapy cognitive impairment with 100% accuracy.

The proposed project aims to test this preliminary prediction model in a new, larger sample with the overarching goal of validating its use for clinical practice. We will enroll 100 newly diagnosed patients with primary breast cancer scheduled for adjuvant chemotherapy who will be assessed prior to any radiation or chemotherapy treatment, 1 month after chemotherapy treatment and again 1 year later. We will also enroll 100 women with breast cancer who have completed chemotherapy treatment.

Additionally, we will enroll matched healthy female controls who will be assessed at yoked intervals. We will combine these data with retrospective data we obtained during a prior study for a total sample of 150 in each group. Data from healthy controls will be used to determine impairment status in patients with breast cancer and to provide a template of typical connectome organization for comparison.

We hypothesize that our machine learning model will accurately predict 1 year post- chemotherapy cognitive impairment and that it will be more accurate than a model that includes patient- related and medical variables alone. We will also examine longitudinal changes in connectome organization associated with impairment subtypes (i.e. persistent vs. late onset impairment) as well as changes in specific functional networks (e.g. default mode, salience, executive-attention and sensory- motor networks). This information will provide novel insights regarding the neural mechanisms of CRCI and may also help us refine our prediction models.

Status: Active But No Longer Recruiting at Stanford

Funded by the National Cancer Institute #R01CA226080-01A1

ProBC2: Prefrontal Cortex Abnormalities Associated With Breast Cancer Chemotherapy-2

Chemotherapy-related cognitive impairment (CRCI), or a decline in memory and other neurocognitive functions that occurs during and after chemotherapy, is associated with reduced quality of life and survival yet remains understudied. Research by our group and others has demonstrated that CRCI is linked to altered brain structure and function from pretreatment to post treatment with neurocognitive impairments being found 20+ years post-treatment. Additionally, breast cancer survivors treated with chemotherapy have accelerated brain aging phenotypes. We have also observed that patients may demonstrate unique trajectories of cognitive impairment that require further study.

Existing prospective studies of cancer and cognition have been limited to relatively short-term post- treatment follow-ups (e.g. 6-12 months), including our past prospective study (CA172145) investigating cognitive function and brain structure/function pre-surgery, 1-month post chemotherapy, and 1-year post chemotherapy. To better understand the long-term trajectory of neurocognitive outcomes in breast cancer survivors, we aim to expand our past prospective study to assess cohorts of women treated with chemotherapy, chemotherapy naïve patients, and healthy controls at yearly intervals for 5 additional years (up to 10 years).

Using non-invasive neuroimaging methods and standardized neuropsychological testing, we will measure long-term changes in neural connectivity, rather than specific regional changes, and cognitive outcomes. Finally, we will explore different trajectories or subtypes of impairment and their neural phenotypes.

By extending our knowledge of long-term neurobiological outcomes and different subtypes of cognitive impairments following breast cancer chemotherapy, the proposed project will significantly advance the understanding of chemotherapy-related cognitive impairments.

Public Health Relevance Statement:
During the last decade there has been progress in defining the neurocognitive changes associated with breast cancer from pretreatment to post treatment, but little is known about these changes after 3 years post treatment. It is possible that cancer-related cognitive impairments result from accelerated aging processes, so we need a better understanding of survivors’ neurocognitive changes beyond 3 years. To begin addressing these limitations, we aim to extend our current prospective study (CA172145), which longitudinally examines cognitive function and brain structure/function pre-surgery to 1-year post chemotherapy. In the proposed study, we will continue to assess our breast cancer cohort at yearly intervals for 5 additional years providing unique longitudinal data up to 10 years post-chemotherapy. The project will extend our knowledge on long-term neurocognitive outcomes following breast cancer chemotherapy

Status: Active and Recruiting

Funded by the National Cancer Institute #5R01CA172145-04