# Integrative subtyping to improve therapeutic options for metastatic hormone receptor-positive breast cancer

> **NIH NIH K08** · STANFORD UNIVERSITY · 2023 · $225,518

## Abstract

Project Summary/Abstract
This is an application for a K08 Award to Dr Jennifer Caswell-Jin, an Instructor and breast oncologist at
Stanford University establishing a career in translational breast cancer genomic research. The Award will
support her career development by providing training in clinical trials, biomarker development, and
bioinformatic analysis of multi-omic data under the expert mentorship of Dr Christina Curtis, computational and
cancer systems biologist, and Dr George Sledge, breast cancer clinical trialist and translational researcher.
The proposed research focuses on the major public health problem of metastatic breast cancer, estimated to
affect over 150,000 women and to cause over 40,000 deaths each year in the United States. Hormone
receptor-positive (HR+) breast cancer is the most common subtype. Eight “integrative” subtypes of HR+ breast
cancer have been identified based on the integration of genome-wide copy number and expression information
in early-stage breast tumors. Four integrative subtypes, together comprising one-quarter of all HR+ early-stage
breast cancers, exhibit a very high risk of distant metastasis; each of these subtypes is characterized by a
distinct area of the genome that exhibits concomitant copy number gain and overexpression. The studies in
this proposal will examine for the first time how integrative subtypes behave after metastasis, with the driving
hypothesis that they may derive benefit from personalized therapeutic approaches. Aim 1 is to investigate the
biology and impact of integrative subtypes in metastatic HR+ breast cancer. We will develop novel approaches
to assess integrative subtypes and will learn whether they change across metastasis, whether they are
associated with timing of metastasis, and whether they have differential lengths of response to standard
therapies. Aim 2 is to evaluate the effects of a novel combination of targeted therapy in two integrative
subtypes of metastatic breast cancer. We will perform a clinical trial that tests a targeted therapeutic approach
in tumors classifying as one of two of the four high-risk integrative subtypes. Because these two subtypes are
defined by focal areas of genomic alteration involving either the fibroblast growth factor receptor ligand (FGF3;
integrative subtype 2) or the fibroblast growth factor receptor (FGFR1; integrative subtype 6), we hypothesize
that these tumors may benefit from FGFR inhibition. Participants in this trial will receive standard endocrine
therapy in combination with CDK4/6 inhibition, as well as an investigational agent that inhibits the fibroblast
growth factor receptor pathway. We will also perform tumor biopsies before and during treatment to evaluate
for changes that occur with this combination targeted therapy approach. Successful completion of the
proposed studies will lay the groundwork for continued efforts to develop a precision oncology approach for
metastatic HR+ breast cancer, with next steps to be propos...

## Key facts

- **NIH application ID:** 10676801
- **Project number:** 5K08CA252457-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jennifer Caswell-Jin
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $225,518
- **Award type:** 5
- **Project period:** 2020-09-03 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10676801

## Citation

> US National Institutes of Health, RePORTER application 10676801, Integrative subtyping to improve therapeutic options for metastatic hormone receptor-positive breast cancer (5K08CA252457-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10676801. Licensed CC0.

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