# Impact of aging on progression and prevention of mammary preneoplasia and cancer

> **NIH NIH UH3** · GEORGETOWN UNIVERSITY · 2020 · $150,000

## Abstract

The research plan will test the overall hypothesis that “Advanced age impacts the experimental outcomes of
the animal model used to study a disease that, in humans, has aging as a major risk factor” (RFA-AG-16-020).
Breast cancer is an age-related cancer in women. We will utilize inducible genetically engineered mouse
models (GEMMs) of mammary epithelial cell-targeted Estrogen Receptor (ER) alpha (Esr1) and Aromatase
(CYP19A1A) over-expression to test the study-specific hypothesis: “Induction of ER alpha and/or aromatase
over-expression in mammary epithelial cells of older aged mice impacts development of mammary
preneoplasia and cancer following induction and/or alters the probability of response to preventive agents
tamoxifen and/or letrozole.” The GEMM to be used parallel human breast cancer progression because
increased ERα and Aromatase expression in the human breast also are associated with development of
preneoplastic ductal hyperplasia, ductal carcinoma in situ, and invasive cancer in women. Specific Aims: 1.
Does the age at which Esr1 or CYP19A1 expression is initiated influence development of mammary
preneoplasia and cancer? Characterize disease development when mice are aged to 12, 18 or 24 months
before induction of Esr1 or CYP19A1 overexpression. 2. Does the age at which Esr1 or CYP19A1 expression
is initiated influence the probability of resistance or response to breast cancer preventives tamoxifen and
letrozole? Characterize response to tamoxifen and letrozole administered at age 18 months after six months
exposure to transgene expression. 3. Evaluate whether or not older mice with delayed Esr1 and/or CYP19A1
transgene induction are better models for human breast preneoplasia and cancer development and/or therapy
study. Significance of the study is that it is a first examination of whether or not the impact ER alpha or
aromatase over-expression is different in older as compared to younger animals and/or whether older animals
respond differentially to intervention with an antihormonal agent such as tamoxifen or letrozole. At present the
majority of women who develop breast cancer are older however preclinical studies and many clinical studies
have not included older subjects. Pathogenesis and therapeutic response are potentially impacted by age and
identification of relevant factors could improve risk assessment and intervention in older women. Expected
results include definition of the impact age on disease and intervention in the models studied, development of
protocols for other investigators who wish to use the same or similar models for studying the impact of aging
on disease pathogenesis or therapy, and information that will aid in understanding why breast cancer incidence
increases with age and insight into its possible prevention.

## Key facts

- **NIH application ID:** 9980299
- **Project number:** 5UH3CA213388-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Priscilla A. Furth
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $150,000
- **Award type:** 5
- **Project period:** 2016-09-16 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980299

## Citation

> US National Institutes of Health, RePORTER application 9980299, Impact of aging on progression and prevention of mammary preneoplasia and cancer (5UH3CA213388-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980299. Licensed CC0.

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