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
基本信息
- 批准号:10783533
- 负责人:
- 金额:$ 8.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AddressAffectAgeBenefits and RisksBiological AssayBody ImageBreastBreast Cancer ModelBreast Cancer TreatmentCancer PrognosisClinicalCommunitiesComplementDiagnosisEstrogen TherapyEstrogen receptor negativeEstrogen receptor positiveFemaleFeminineGenderGoalsGonadal Steroid HormonesGrantGuidelinesHistologyImmuneImmunofluorescence ImmunologicIndividualKnowledgeMass Spectrum AnalysisMeasuresMedicalModelingMolecularMusParentsPatient riskPatientsPopulationStainsTreatment outcomeWell in selfWorkalpelisibassigned male at birthcancer riskcancer therapycarcinogenesiscis-femalecis-maleclinical translationemotional distressexperimental studygender affirmationgender affirming hormonesimprovedmalemalignant breast neoplasmmouse modeltranscriptome sequencingtransfemininetransgendertreatment strategytumortumor growth
项目摘要
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 CA267088)是为了了解变性女性患者的风险和
乳腺癌(BC)期间继续性别肯定雌激素治疗(ET)的好处
治疗。变性女性在出生时被指定为男性,大多数人追求ET来确认他们的
女性身份。随着变性人人口的增加,将有相当数量的
跨性别者在未来20到50年内随着年龄的增长而面临患癌症的风险。为
被诊断为BC的变性患者,他们是否能继续下去没有临床指南
在BC治疗期间接受ET治疗,以及ET是否影响BC的预后。这个
对于变性人来说,停止使用性别肯定激素是不可取的,因为它
极大地影响他们的情绪健康和身体形象,并加剧他们的癌症诱因
精神上的痛苦。为了解决临床上的风险和益处问题,
变性患者在BC治疗期间继续ET,我们父母R21的总体策略
是使用三种BC小鼠模型-Pik3camut、Brca1mut或Tp53mut-来理解
ET对BC治疗结局的影响。我们将比较肿瘤生长速度,乳腺组织学,
以及在BC期间继续和停止ET的雄鼠之间的治疗结果
使用alpelisib(对于Pik3camut肿瘤)、olaparib(对于BRCA mut肿瘤)或eribuin(对于
Tp53抑制肿瘤)。在第一年,我们完成了Brca1mut肿瘤和奥拉帕利的实验
治疗。在第二年的上半年,我们将专注于完成Tp53mut的实验
肿瘤来补充我们的Brca1mut发现。这将使我们能够大致了解
ET如何影响雌激素受体阴性(ER-)BC治疗。本副刊提出三点建议
额外的分子分析来解释我们对Brca1mut和Tp53mut肿瘤模型的发现:1)到
用质谱仪测定肿瘤中奥拉帕利布/淫羊藿苷的水平;2)对ER-肿瘤进行轮廓分析
利用RNAseq鉴定性别和性激素相关的影响分子机制
BC治疗结果;以及3)评估性别和/或性激素对肿瘤的影响
免疫环境采用多重免疫荧光染色。总体而言,我们的工作将
有直接和即时的临床翻译,以告知ER-BC治疗选项和决定
对于变性女性群体来说。我们的发现也将告诉我们为什么在男性中发生BC
比女性更具攻击性,从而改进了对顺性男性和
患有不列颠哥伦比亚省的女性也是。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Yu Jing Jan Heng其他文献
Yu Jing Jan Heng的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Yu Jing Jan Heng', 18)}}的其他基金
Gender-Affirming Testosterone Therapy on Breast Cancer Risk and Treatment Outcomes
性别肯定睾酮疗法对乳腺癌风险和治疗结果的影响
- 批准号:
10912193 - 财政年份:2023
- 资助金额:
$ 8.99万 - 项目类别:
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
- 批准号:
10543116 - 财政年份:2021
- 资助金额:
$ 8.99万 - 项目类别:
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
- 批准号:
10350731 - 财政年份:2021
- 资助金额:
$ 8.99万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 8.99万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 8.99万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 8.99万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 8.99万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 8.99万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 8.99万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 8.99万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 8.99万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 8.99万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 8.99万 - 项目类别:
Miscellaneous Programs