Current Research Projects
At this time, we are resuming our human subject research with increased safety precautions, in accordance with guidelines set forth by Stanford University. The safety of out participants is our number one priority in the COVID-19 Pandemic.
ProBC2: Prefrontal Cortex Abnormalities Associated With Breast Cancer Chemotherapy-2
Chemotherapy-related cognitive impairment (CRCI) is associated with reduced quality of life and survival making it a significant problem that remains understudied. Research by our group and others has demonstrated that CRCI is associated with altered brain structure and function from pretreatment to post treatment. There is significant overlap between chemotherapy actions and physiologic processes involved in aging. Neurocognitive have been found in patients up to 20+ years post- treatment and work by our group and others suggests an accelerated brain aging phenotype in breast cancer survivors treated with chemotherapy. We have also observed that patients may demonstrate unique trajectories of cognitive impairment that require further study.
Existing prospective, longitudinal studies of cancer and cognition, including our own, have been limited to relatively short-term post- treatment follow-ups (e.g. 6-12 months). 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, 1-month post chemotherapy, and 1-year post chemotherapy. We will continue 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, we will advance our original aims from the initial project to measure very long- term neurobiologic outcomes with an emphasis on the assessment of neural connectivity rather than specific regional changes. We will also examine very long-term cognitive outcomes as measured by standardized neuropsychological testing. Finally, we will explore different trajectories or subtypes of impairment and their neural phenotypes.
The proposed project will significantly advance the understanding of chemotherapy-related cognitive impairments by extending our knowledge on very long-term neurobiological outcomes along with the different subtypes of cognitive impairments and associated neural profiles following breast cancer chemotherapy.
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 how the neurocognitive changes beyond 1-3 years post treatment. It is possible that cancer related cognitive impairments result from accelerated aging processes, and if 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 competing renewal 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 proposed project will extend our knowledge on very long-term neurocognitive outcomes following breast cancer chemotherapy
Status: Recruiting participants who were in ProBC
Funded by the National Cancer Institute. #5R01CA172145-04
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: Recruiting New Participants
Funded by the National Cancer Institute #R01CA226080-01A1
MOSAIC: Management of Insomnia in Breast Cancer Patients
This research is designed to determine the efficacy of the BBT-I in comparison with the attention-matched behavioral control in reducing insomnia, fatigue, and cognitive difficulties in breast cancer patients. In addition, this study will examine the potential involvement of moderators (age, depression, anxiety, and hot flashes), specific behavioral mechanisms (maladaptive sleep behaviors, dysfunctional beliefs and attitudes), and physiological mechanisms (dysregulated circadian rhythms, disrupted wake-sleep cycles, and autonomic tone) as potential mediators of intervention-related changes in insomnia and the secondary outcomes of fatigue and cognitive difficulties.
To address these aims, 180 breast cancer patients with acute insomnia during chemotherapy treatment will be recruited and randomized to receive either BBT-I or a behavioral control focused on Healthy Eating Education.
Each intervention condition will consist of 2 face-to-face sessions + 4 phone calls, delivered over a period of six weeks. Assessments will include sleep diary, questionnaires, neuropsychological testing, actigraphy, heart rate variability measurement, and salivary cortisol collection at baseline, post-intervention, and 6- and 12 months follow ups.
By offering this intervention during chemotherapy when patients are just beginning to develop insomnia, we hope to alleviate and avoid the development of chronic insomnia in the survivorship phase.
Status: Not Recruiting
Funded by the National Cancer Institute. #5R01CA181659-02