# Biologic and Patient Variation Affecting Breast Cancer Treatment Efficacy

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $7,953

## Abstract

Aside from non-melanoma skin cancer, breast carcinoma is the most commonly diagnosed malignancy among
women, with approximately 1.7 million new diagnoses annually worldwide. Over the past decades there have
been substantial improvements in the 5-year survival rates for women diagnosed with breast cancer, however
the long-term risk of breast cancer recurrence remains high (20–40% over approximately 20 years). There is a
dearth of information regarding the epidemiology of breast cancer recurrence, and a need to identify modifiable
patient and tumor characteristics that affect the risk of breast cancer recurrence. Premenopausal women
diagnosed with estrogen receptor positive breast cancer are prescribed tamoxifen for up to ten years to prevent
breast cancer recurrence. Previous studies suggest that patient adherence is low, yet the impact among
premenopausal women has not yet been evaluated. Resistance to tamoxifen therapy may arise from increased
intratumoral expression of estrogen-related metabolites. Biomarkers that are predictive of tamoxifen resistance
would identify patients amenable to additional therapies to prevent recurrence. The overarching goal of this
research proposal is to evaluate biomarkers, patient characteristics, and treatment-related factors that help
explain the variation in effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence. To
address this goal, this project will leverage resources from the Danish healthcare registry system, which includes
nearly complete high-quality data with information on breast cancer recurrence. Aim 1a will describe the trends
in breast cancer recurrence over the past 35 years and aim 1b will estimate the population-level effect of the
introduction of three biomarker-driven adjuvant therapies—tamoxifen, aromatase inhibitors, and trastuzumab—
on breast cancer recurrence risk using summary level data from the Danish Cancer Registry. These aims will
describe the trends in breast cancer recurrence over time, using Poisson regression and will estimate the
population-level causal effect of the introductions of tamoxifen, aromatase inhibitors, and trastuzumab as well
as any major changes in guidelines to the indication for each adjuvant therapy. This aim will use the newly
developed trend-in-trend analytic method to estimate the population-level impact of the introduction of each
adjuvant therapy. Aim 2 will investigate the impact of adherence to endocrine therapy on breast cancer
recurrence in an exclusively premenopausal cohort. Aim 3 will evaluate the effect of two enzymes, 17β-
hydroxysteroid dehydrogenase 1 and 2, that regulate the intratumoral concentration of estrogen-related
metabolites as markers of tamoxifen resistance in an exclusively premenopausal cohort. The results from this
proposed research project will provide insight into the epidemiology of breast cancer recurrence. Furthermore, it
will lead to improved understanding of the effect of patient adherence to adju...

## Key facts

- **NIH application ID:** 9934860
- **Project number:** 5F31CA239566-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lindsay Jane Collin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $7,953
- **Award type:** 5
- **Project period:** 2019-05-08 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934860

## Citation

> US National Institutes of Health, RePORTER application 9934860, Biologic and Patient Variation Affecting Breast Cancer Treatment Efficacy (5F31CA239566-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934860. Licensed CC0.

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