The overall purpose of this trial is to confirm the efficacy of Memory and Attention Adaptation Training (MAAT), a cognitive-behavioral therapy (CBT) for treatment of chemotherapy-related cognitive dysfunction among (female or male) breast cancer survivors. This is a multi-center, multi-clinician randomized control trial (MAAT vs. supportive therapy attention control condition). This trial will also evaluate a sub-sample of survivors pre-and post treatment with functional magnetic resonance imaging (fMRI) in a working memory task to evaluate pre-to-post treatment brain activation patterns to elucidate underlying mechanisms of clinical therapeutic change.

The primary aim of this multi-site, multi-clinician randomized controlled trial is to determine if Memory and Attention Adaptation Training (MAAT), a cognitive-behavioral therapy (CBT) intervention, can improve self-reported and objectively measured cognitive functioning in breast cancer survivors who previously received chemotherapy. Breast cancer survivors (Stage I-III) who were treated with chemotherapy 1-5 years prior to enrollment and who have subjective cognitive complaints may be eligible for this study. After eligibility is confirmed, participants will complete baseline assessments of subjective and objective memory and attention functioning as well as behavioral rating scales, and will be randomized to MAAT or Supportive Therapy (ST; to control for therapist time and attention) for 8 weeks. Both treatments (MAAT and ST) will be delivered through videoconferencing using mobile (smartphone, laptop or other electronic device) in order to reduce survivor travel or time away from work or family. Data collection methods will include telephone- and web-administered measures of subjective and objective cognitive function, as well as various behavioral ratings. Outcome assessments will be conducted post-treatment and at 6-month follow-up. It is hypothesized that MAAT participants will have significantly improved scores of self-reported cognitive impairments and objective neurocognitive test scores (on verbal memory and processing speed) at post-treatment and 6-month follow-up compared to participants randomized to ST. In addition, willing and eligible participants will be asked to complete a functional MRI working memory task at baseline and post-treatment, to examine whether those who receive MAAT show greater increase in brain network activation than those who receive ST. This may advance understanding of the neural mechanisms underlying improvement of objective and self-reported cognitive function after chemotherapy. The sample size (n=100/group) will allow for a 10-15% drop out-rate and still provide 80% power to detect group differences using two (Group: MAAT vs. ST) by 3 (time: baseline, posttreatment, 6-month follow-up) ANCOVA at alpha=0.05. Potential baseline differences between MAAT and ST groups on primary outcome variables or other factors that may affect cognition (e.g., anxiety, fatigue or depression) will be evaluated as potential covariates, although such differences due to randomization are not anticipated.

Inclusion Criteria:

1. Diagnosis of stage I-III breast cancer
2. 1-5 years post-treatment and currently disease free
3. Treatment involved adjuvant or neoadjuvant chemotherapy
4. Report cognitive problems of memory and concentration attributed to chemotherapy with a score of 10 or below on the FACT-Cog Impact on Quality of Life Scale (a score ~1SD below pre-chemotherapy treatment norms; this criterion was used in our prior R21 study, ensures a clinically meaningful level of cognitive concerns,41 and discriminates high and low PCI scores in prior research42)
5. Able to speak and read English
6. Age >18
7. Able to provide IRB-approved written informed consent
8. Willing to use videoconferencing.

Exclusion Criteria:

1. Previous CNS radiation, intrathecal therapy, or CNS-involved surgery
2. Previous cancer history with the exception of non-melanoma skin cancer
3. Previous exposure to chemotherapy with another cancer or due to other medical condition (e.g., methotrexate exposure for treatment of rheumatoid arthritis)
4. Significant neurodevelopmental, neurobehavioral, or medical risk factors likely to affect cognitive functioning (e.g., history of neurological disorder or TBI of greater than mild severity, such as loss of consciousness >30 minutes, medical disorder that is unstable or likely to affect cognition such as metabolic disorder, heart attack or stroke, uncontrolled diabetes or endocrine dysfunction)
5. Currently meeting DSM-5 mental disorder criteria, including but not limited to neurodevelopmental, substance abuse, mood (e.g., Maj.Dep), anxiety, or psychotic disorders
6. Scoring 3 or below on the 6-item cognitive screen designed to detect severe memory disorders;43
7. Severe uncorrected sensory impairment (severe hearing or visual impairment)

NIH funded study - public database

We anticipate a completed data set in approximately December of 2025 and will make de-identified data available to qualified investigators for a period of 3 years after publication of primary results in a peer reviewed journal.

De-identified data sharing criteria include (for quality assurance): 1) Qualified researchers who have obtained IRB approval from their institution; 2) Sign a Data Use Agreement (DUA); 3) Agree to NIH, IRB policies and HIPAA requirements regarding privacy, data security and ethical practices; 4) The DUAs will ensure that data will be used only for the specific research purposes outlined in the DUA; 5) No personally identifiable or protected health information will be shared outside of University of Pittsburgh/Indiana University research staff who have a need to know this information for the purposes of the study; 6) Individual participant's data will not be disseminated; 7) Data access will be protected under security measures including encryption and password protection, and that the data will be destroyed or returned to the University of Pittsburgh/Indiana University study team after completion of relevant analyses. Collaborative analyses with project investigators are encouraged.