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.

项目概要 我们的母公司 R21 拨款 (R21 CA267088) 旨在了解跨性别患者的风险和 乳腺癌 (BC) 期间持续进行性别肯定雌激素治疗 (ET) 的益处 跨性别个体在出生时被指定为男性，并且大多数寻求 ET 来确认自己的性别。 随着跨性别人口的增加，将会出现大量的女性身份。 跨性别者在未来 20 至 50 年内随着年龄的增长面临患癌症的风险。 诊断为 BC 的跨女性患者，是否可以继续治疗尚无临床指南 在 BC 治疗期间接受 ET，以及 ET 是否影响其 BC 预后。 对跨性别者停止使用性别确认激素是不可取的，因为 极大地影响他们的情绪健康和身体形象，并加剧他们诱发癌症的风险 为了解决情绪困扰的风险和益处的临床问题。 跨性别患者在 BC 治疗期间继续 ET，我们母公司 R21 的总体策略 的方法是使用三种 BC 小鼠模型——Pik3camut、Brca1mut 或 Tp53mut——来了解 我们将比较肿瘤生长率、乳腺组织学、 以及在 BC 期间继续和停止 ET 的雄性小鼠之间的治疗结果 使用 alpelisib（用于 Pik3camut 肿瘤）、olaparib（用于 Brca mut 肿瘤）或艾日布林（用于 第一年，我们完成了 Brca1mut 肿瘤和奥拉帕尼的实验。 第二年上半年，我们将重点完成 Tp53mut 的实验。 肿瘤来补充我们的 Brca1mut 研究结果，这将使我们能够获得总体概述。 ET 如何影响雌激素受体阴性 (ER-) BC 治疗 本补充提出了三种方法。 其他分子检测来解释我们对 Brca1mut 和 Tp53mut 肿瘤模型的发现：1) 使用质谱法测量肿瘤中的奥拉帕尼/艾日布林水平；2) 分析 ER-肿瘤 使用 RNASeq 识别性别和性激素相关的分子影响机制 BC 治疗结果；3) 评估性别和/或性激素对肿瘤的影响 总的来说，我们的工作将使用多重免疫荧光染色。 进行直接、即时的临床转化，为 ER-BC 治疗选择和决策提供信息 对于跨性别群体来说，我们的研究结果还将告诉我们为什么 BC 发生在男性身上。 比女性更具攻击性，从而改善了顺性别男性和女性的治疗策略 女性也患有 BC。