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Gender-affirming estrogen therapy and breast cancer treatment outcome

性别肯定雌激素治疗和乳腺癌治疗结果

基本信息

批准号：
10543116
负责人：
Yu Jing Jan Heng
金额：
$ 20.04万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-21 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10543116
关键词：
Adult Adverse effects Affect Age Animal Model Body Image Breast Breast Cancer Model Breast Cancer Risk Factor Breast Cancer Treatment C57BL/6 Mouse Cancer Prognosis Case Study Clinical Communities Crossbreeding Data Dependence Diagnosis Disease Estradiol Estrogen Receptors Estrogen Therapy Estrogen receptor negative Estrogen receptor positive Estrogens FVB/N Mouse Feminine Feminization Genetic Engineering Goals Gonadal Steroid Hormones Guidelines Healthcare Histology Hormone replacement therapy Hormones Immunocompetent Implant Individual Knowledge Link Malignant Neoplasms Malignant neoplasm of prostate Mammary Neoplasms Medical Medical Research Methods Modeling Morbidity - disease rate Mus Oral Administration Outcome Patient Care Personal Satisfaction Plasma Population Postmenopause Pre-Clinical Model Preparation Prevalence Publishing Reporting Research Risk Route Techniques Transplantation Treatment outcome Well in self Work Youth alpelisib assigned male at birth bone health cancer care cancer health disparity cancer risk cancer subtypes cancer therapy carcinogenesis cardiovascular health cis-female cis-male dosage emotional distress follow-up gender affirmation gender affirming hormone therapy improved male malignant breast neoplasm mortality mortality disparity mouse model neglect neoplastic cell pre-clinical receptor expression sex standard of care transfeminine transgender treatment strategy tumor tumor growth

项目摘要

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.

项目总结