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.

项目概要我们在该提案中的总体目标是建立乳腺癌（BC）和乳腺癌的跨性别小鼠模型为接受雌激素治疗 (ET) 的跨女性个体制定 BC 治疗策略。个体在出生时就被指定为男性，其中大多数人追求 ET 来确认自己的女性身份。让男性身体长时间接触极高的外源性雌激素，以达到与顺性别女性相当的水平引起了人们对 ET 的不利影响的担忧。他们的健康状况，但目前尚不清楚 ET 如何调节他们终生患乳腺癌 (BC) 的风险，以及如果他们诊断为 BC，ET 如何影响他们的 BC 预后其他小组已经确定了跨性别激素。治疗小鼠模型，研究性别肯定激素治疗对骨骼和骨骼的影响心血管健康尚无动物模型来研究跨性别激素之间的联系。该提案将开发一种女性化的跨性别小鼠模型，以确定 ET 影响 BC 治疗结果的程度我们将移植三种类型的乳腺肿瘤——Pik3camut、 Brca1mut 或 Tp53mut——进入接受 ET 的雄性小鼠中，我们将比较肿瘤生长率、乳腺组织学和在用 alpelisib 进行 BC 治疗期间继续和停止 ET 的雄性小鼠之间的治疗结果（针对 Pik3camut 肿瘤）、奥拉帕尼（针对 Brca mut 肿瘤）或艾日布林（针对 Tp53mut 肿瘤）我们的长期目标是我们的临床前模型可用于为跨性别群体制定 BC 治疗策略。制定治疗其他 BC 亚型以及其他激素依赖性恶性肿瘤的策略，例如我们的工作不仅会减少跨性别癌症的差异；研究结果将有助于我们了解 BC 性激素依赖性，从而改善治疗也适用于患有 BC 的顺性别男性和女性的策略。