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; 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 我们的父母R21赠款（R21 CA267088）是要了解transfeminine患者的风险和 继续性别疗法雌激素疗法（ET）的好处（BC） 治疗。妇女的个体在出生时被分配男性，大多数人追求ET遭受他们的痛苦 女性身份。随着跨性别人口的增加，将有大量 跨性别者在接下来的20至50年内患有癌症风险。为了 经过诊断为卑诗省的转身女性患者，没有临床指南是否可以继续 在卑诗省治疗期间接受ET，以及ET是否影响其BC预后。这 跨性别者的性别表达激素的中断是不受欢迎的 极大地影响了他们的情感健康和身体形象，并使他们的癌症引起 情绪困扰。为了解决临床问题的风险和利益 transfeminine患者在卑诗省治疗期间继续ET，这是我们父母R21的总体策略 是要使用BC的三种鼠标模型 - PIK3CAMUT，BRCA1MUT或TP53MUT ET对BC治疗结果的影响。我们将比较肿瘤生长速率，乳房组织学， 以及在卑诗省继续前进和终止ET的雄性小鼠之间的治疗结果 用Alpelisib（用于PIK3Camut肿瘤），Olaparib（用于BRCA MUT肿瘤）或eribulin（用于 TP53MUT肿瘤）。在第一年，我们完成了BRCA1MUT肿瘤和Olaparib的实验 治疗。在第二年的上半年，我们将专注于完成TP53MUT的实验 肿瘤以完成我们的BRCA1MUT发现。这将使我们获得一般概述 ET如何影响雌激素受体阴性（ER-）BC治疗。这项补充提案三个 其他分子测定方法来解释我们对BRCA1MUT和TP53MUT肿瘤模型的发现：1） 使用质谱法测量肿瘤中olaparib/eribulin水平； 2）剖析肿瘤 使用RNASEQ鉴定性别和性激素相关的分子机制影响 BC治疗结果； 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的免疫环境。总的来说，我们的工作将 具有直接和立即的临床翻译，以告知ER-BC治疗选择和决策 对于跨女性社区。我们的发现还将告知我们为什么卑诗省发生在男性中 比女性更具侵略性 卑诗省的妇女。