Admin Suppl Gender-affirming estrogen therapy and breast cancer treatment outcome

行政补充性别肯定雌激素治疗和乳腺癌治疗结果

• 批准号: 10783533
• 负责人: Yu Jing Jan Heng
• 金额: $ 8.99万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10783533
• 关键词: Address; Affect; Age; Benefits and Risks; Biological Assay; Body Image; Breast; Breast Cancer Model; Breast Cancer Treatment; Cancer Prognosis; Clinical; Communities; Complement; Diagnosis; Estrogen Therapy; Estrogen receptor negative; Estrogen receptor positive; Female; Feminine; Gender; Goals; Gonadal Steroid Hormones; Grant; Guidelines; Histology; Immune; Immunofluorescence Immunologic; Individual; Knowledge; Mass Spectrum Analysis; Measures; Medical; Modeling; Molecular; Mus; Parents; Patient risk; Patients; Population; Stains; Treatment outcome; Well in self; Work; alpelisib; assigned male at birth; cancer risk; cancer therapy; carcinogenesis; cis-female; cis-male; clinical translation; emotional distress; experimental study; gender affirmation; gender affirming hormones; improved; male; malignant breast neoplasm; mouse model; transcriptome sequencing; transfeminine; transgender; treatment strategy; tumor; tumor growth

Project Summary Our parent R21 grant (R21 CA267088) was to understand transfeminine patients’ risks and benefits of continuing gender-affirming estrogen therapy (ET) during their breast cancer (BC) treatment. Transfeminine individuals are assigned male at birth and most pursue ET to affirm their feminine identity. As the transgender population increases, there will be a substantial number of transgender individuals at risk for cancer as they age within the next 20 to 50 years. For transfeminine patients diagnosed with BC, there is no clinical guideline whether they can continue receiving ET during BC treatment, and whether ET affects their BC prognosis. The discontinuation of gender-affirming hormones for a transgender individual is undesirable as it greatly affects their emotional well-being and body image, and compounds their cancer-induced emotional distress. In order to address the clinical question of the risks and benefits of transfeminine patients continuing ET during BC treatment, the overall strategy of our parent R21 was to use three mouse models of BC—Pik3camut, Brca1mut, or Tp53mut—to understand the effect of ET on BC treatment outcomes. 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). In Year 1, we completed the experiments for Brca1mut tumors and olaparib treatment. For the first half of Year 2, we will focus on completing experiments for Tp53mut tumors to complement our Brca1mut findings. This will allow us to obtain a general overview of how ET affects estrogen receptor negative (ER-) BC treatment. This supplement proposes three additional molecular assays to explain our findings for Brca1mut and Tp53mut tumor models: 1) to measure olaparib/eribulin levels in the tumors using mass spectrometry; 2) to profile ER- tumors using RNASeq to identify gender and sex-hormone related molecular mechanisms influencing BC treatment outcomes; and 3) assess the effect of gender and/or sex-hormone on tumor immune contexture using multiplex immunofluorescence staining. Collectively, our work will have direct and immediate clinical translation to inform ER- BC treatment options and decisions for the transfeminine community. Our findings will also inform us why BC occurring in males are more aggressive than in females, thus improving treatment strategies for cisgender men and women with BC as well.

项目摘要 我们的母公司R21赠款（R21 CA 267088）是为了了解变性患者的风险， 在乳腺癌（BC）期间继续性别肯定雌激素治疗（ET）的益处 治疗变性人在出生时被分配为男性，大多数人追求ET以确认他们的性别。 女性身份随着跨性别人口的增加，将有大量的 跨性别者在未来20至50年内随着年龄的增长而有患癌症的风险。为 诊断为BC的跨女性患者，没有临床指南，他们是否可以继续 在BC治疗期间接受ET，以及ET是否影响BC预后。的 对变性人停止使用性别确认激素是不可取的，因为它 极大地影响了他们的情绪健康和身体形象，并加剧了他们的癌症诱导 情绪困扰为了解决风险和受益的临床问题， 跨女性患者在BC治疗期间继续ET，我们的父母R21的总体策略 使用三种BC-Pik 3camut、Brca 1 mut或Tp 53 mut小鼠模型， ET对BC治疗结果的影响。我们将比较肿瘤生长率，乳腺组织学， 在BC期间继续和停止ET的雄性小鼠之间的治疗结果 用alpelisib（用于Pik 3camut肿瘤）、olaparib（用于Brca mut肿瘤）或eribulin（用于 TP 53 mut肿瘤）。在第一年，我们完成了Brca 1 mut肿瘤和奥拉帕尼的实验。 治疗在第二年的上半年，我们将专注于完成TP 53 mut的实验 肿瘤来补充我们的Brca 1 mut发现。这将使我们能够获得一个总体概述， ET如何影响雌激素受体阴性（ER-）BC治疗。本补充建议三 其他分子测定来解释我们对Brca 1 mut和Tp 53 mut肿瘤模型的发现：1） 使用质谱法测量肿瘤中奥拉帕尼/艾日布林水平; 2）分析ER-肿瘤 使用RNASeq鉴定性别和性激素相关的分子机制， BC治疗结果;以及3）评估性别和/或性激素对肿瘤的影响 使用多重免疫荧光染色进行免疫构造。我们的工作将 有直接和立即的临床翻译，以告知ER- BC治疗方案和决定 为变性人社区服务我们的研究结果还将告诉我们为什么BC发生在男性中， 比女性更具侵略性，从而改善了顺性别男性的治疗策略， 女性也有BC。