# A longitudinal, nationally representative study of cognition-related effects of breast cancer and its treatment

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $339,008

## Abstract

ABSTRACT
More breast cancer patients are treated with anti-estrogen agents, such as aromatase inhibitors (AIs), than
with any treatment other than surgery. Due to their effectiveness, recent guidelines for postmenopausal women
advise extending AI therapy to 10-years duration. Therefore, exposure to AIs among the more than 3.5 million
breast cancer survivors will soon increase. A major concern of breast cancer survivors is therapy-induced
cognitive dysfunction. About 75% of women suffer cancer-related cognitive impairment during chemotherapy
treatment, which persists for months to years. There are theoretical and empirical reasons to believe that
cognitive impairment may also occur with estrogen deprivation. Surprisingly, there are few empirical human
studies of AI effects on cognition; none with cognition measured pre-cancer. Leveraging 18 years of data from
the Health and Retirement Studies―a nationally-representative, longitudinal survey augmented by Medicare
medical and pharmaceutical claims, we propose a longitudinal study designed to: (1) Characterize breast
cancer survivors’ cognitive functioning post-initiation of adjuvant AI therapy over a 60-month period using a
validated neuropsychological measure and compare their performance to those of (i) women with incident
breast cancer who did not receive AI therapy and (ii) non-cancer controls. Cross-sectional analyses
corresponding to roughly one-, three-, and five years post-AI therapy initiation will provide estimates of early
and late effects of AIs; (2) Contrast the longitudinal trajectory of cognitive functioning preceding and following
cancer diagnosis and treatment among women treated with an AI to those of (i) cancer survivors who did not
receive AI therapy and (ii) cancer-free controls, over an 18-year span. We anticipate a gradual decline in
cognitive functioning among cancer-free women over the study period. The AI group, however, is expected to
exhibit a steeper downward slope after AI initiation, indicating an adverse AI effect on cognition above and
beyond normal cognitive aging; and (3) Quantify the tradeoff between overall and disease-free life years and
cognitive functioning among women with incident breast cancer undergoing different adjuvant therapies. Using
findings from Aim 2 combined with parameter estimates from analyses of time to disease recurrence and time
to death, we will calculate overall and disease-free life years by cognitive functioning for various scenarios of
patients’ sociodemographic characteristics and cancer treatment(s). Results from these analyses will provide
rigorous evidence regarding the potentially adverse effects of AI exposure on cognition that may serve as the
basis for clinical interventions. They will also generate population-level estimates of survival and cognitive
decline attributable to AI and other cancer-treatments (beyond normal cognitive aging) that could be used to
better inform patients about “real world” tradeoffs of different breast...

## Key facts

- **NIH application ID:** 10900593
- **Project number:** 5R01CA264326-03
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Ann B Nattinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $339,008
- **Award type:** 5
- **Project period:** 2022-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900593

## Citation

> US National Institutes of Health, RePORTER application 10900593, A longitudinal, nationally representative study of cognition-related effects of breast cancer and its treatment (5R01CA264326-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10900593. Licensed CC0.

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