# Gender-affirming estrogen therapy and breast cancer treatment outcome

> **NIH NIH R21** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $245,438

## Abstract

Project Summary
Our overall objectives in this proposal are to establish a cross-sex mouse model for breast cancer (BC) and
develop BC treatment strategies for transfeminine individuals receiving estrogen therapy (ET). Transfeminine
individuals are assigned male at birth and a majority of them pursue ET to affirm their feminine identity.
Exposing the male body to extremely high exogenous estrogen over extended periods in order to achieve
levels comparable to cisgender women raises concerns about the adverse effects of ET. ET is essential for
their wellbeing but it remains unclear how ET modulates their lifetime breast cancer (BC) risk and, if they are
diagnosed with BC, how ET affects their BC prognosis. Other groups have established cross-sex hormone
treatment mouse models to investigate the impact of gender affirming hormone therapy on bone and
cardiovascular health. There is no animal model to investigate the link between cross-sex hormone
treatment and cancer. This proposal will develop a cross-sex mouse model of feminization to determine the
extent which ET affects BC treatment outcomes. We will transplant three types of breast tumors—Pik3camut,
Brca1mut, or Tp53mut—into male mice receiving ET. We will compare tumor growth rates, breast histology, and
treatment outcomes between male mice that continue and discontinue ET during BC treatment with alpelisib
(for Pik3camut tumors), olaparib (for Brca mut tumors), or eribulin (for Tp53mut tumors). Our long-term goal is to
establish BC treatment strategies for the transgender community. Our preclinical model can be utlilized to
develop strategies to treat other BC subtypes as well as other hormone- dependent malignancies such as
prostate cancer. Our work will not only have implications in reducing transgender cancer disparities; our
findings will contribute to our understanding of sex hormone dependencies in BC thus improving treatment
strategies for cisgender men and women with BC as well.

## Key facts

- **NIH application ID:** 10350731
- **Project number:** 1R21CA267088-01
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Yu Jing Jan Heng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $245,438
- **Award type:** 1
- **Project period:** 2021-12-21 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350731

## Citation

> US National Institutes of Health, RePORTER application 10350731, Gender-affirming estrogen therapy and breast cancer treatment outcome (1R21CA267088-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10350731. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*