Body composition and breast cancer survival: immune and metabolic biomarkers in breast tumors - Disparities Supplement

身体成分和乳腺癌生存：乳腺肿瘤中的免疫和代谢生物标志物 - Disparities Supplement

• 批准号: 10712034
• 负责人: Elizabeth Marjorie Cespedes Feliciano
• 金额: $ 23万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712034
• 关键词: Address; Adipose tissue; Administrative Supplement; Biological Markers; Black race; Body Composition; Body fat; Body mass index; Breast; Breast Cancer Patient; CD8-Positive T-Lymphocytes; Cancer Prognosis; Cell Proliferation; Collaborations; Data; Disease; Disparity; Drug or chemical Tissue Distribution; Eligibility Determination; Epidemiology; Ethnic Origin; FRAP1 gene; Gene Expression; Genes; Goals; High Prevalence; Hormonal; Hormone Receptor; Immune; Impairment; Infrastructure; Integrated Health Care Systems; Intervention; Link; Malignant Neoplasms; Mammary Neoplasms; Measures; Medical; Medical Oncology; Metabolic; Metabolic Pathway; Metabolic dysfunction; Molecular; Neighborhoods; Not Hispanic or Latino; Obesity; Outcome; PIK3CG gene; Pathology; Pathway interactions; Patient Care; Patients; Physiological; Pre-Clinical Model; Race; Research; Research Personnel; Retrieval; Risk; Risk Factors; Role; Sampling; Series; Socioeconomic Status; Specimen; T-Lymphocyte; Tumor Biology; Tumor Immunity; Visceral; Waist-Hip Ratio; Woman; Work; analysis pipeline; black women; breast cancer survival; cancer care; cancer health disparity; cancer therapy; cohort; comorbidity; disparity reduction; ethnic disparity; ethnic diversity; exhaust; exhaustion; experience; follow-up; hormone receptor-negative; human data; lifestyle intervention; malignant breast neoplasm; modifiable risk; molecular subtypes; mortality; parent grant; racial difference; racial disparity; racial diversity; study population; subcutaneous; survival prediction; therapy resistant; tumor; tumor microenvironment; tumor progression

ABSTRACT This Supplement to R01CA251589 “Body composition and breast cancer survival: immune and metabolic biomarkers in breast tumors” responds to the PAR-22-114 “Administrative Supplements to Support Cancer Disparity Collaborative Research.” The long-term goal is to reduce the disproportionate burden of breast cancer mortality experienced by non-Hispanic black (NHB) women by understanding the role of a key, modifiable risk factor: excess adiposity. Preclinical models indicate that excess adiposity impairs anti-tumor immunity and alters metabolic and cell proliferation pathways to promote cancer progression. Given the markedly higher prevalence of obesity (body mass index [BMI] >30-kg/m2) in NHB vs. vs. non-Hispanic white (NHW) women, obesity is assumed to contribute to disparities in survival. Yet, BMI does not consistently predict survival after breast cancer in NHB women or in women hormone receptor negative breast tumors, which are more common in NHB women. Preliminary studies suggest that more specific measures of adipose tissue distribution outperform BMI to predict breast cancer survival. Given racial differences in adipose tissue distribution at a given BMI, there is a need to study body composition to elucidate the role of adiposity in generating racial disparities. This administrative supplement establishes a new collaboration between a cancer disparities expert and a study team with expertise in epidemiology, tumor biology and breast medical oncology. The parent grant seeks to understand how systemic factors such as patient body composition impact the local breast tumor microenvironment and therefore breast cancer survival. With this administrative supplement, we expand those aims to include a disparities focus by comparing NHB vs. NHW women. We will expand representation of tumors from NHB women in our study, and conduct a series of analyses focused on racial disparities. Specifically, we will examine: racial differences in the distribution of visceral v. subcutaneous adiposity and in associations of these adipose tissue depots with survival (Aim 1); racial differences in the associations of each adipose tissue depot with expression of immune and metabolic genes in the breast tumor microenvironment (Aim 2); and racial differences in the associations of immune and metabolic genes in the breast TME with survival (Aim 3). Potential harms of excess adiposity may be mitigated through both medical and lifestyle interventions; thus, understanding the role of adiposity in generating racial disparities in breast cancer is a high priority not only for research but patient care.

摘要 R 01 CA 251589“身体组成和乳腺癌生存：免疫和代谢”的补充 乳腺肿瘤中的生物标志物”对PAR-22-114“支持癌症的行政补充”的回应 差异合作研究”。长期目标是减少乳腺癌不成比例的负担 非西班牙裔黑人（NHB）妇女经历的癌症死亡率， 可改变的危险因素：过度肥胖。 临床前模型表明，过度肥胖损害抗肿瘤免疫，改变代谢和细胞 增殖途径来促进癌症进展。鉴于肥胖症（身体）的患病率明显较高， 体重指数[BMI] >30-kg/m2），肥胖被假定为 造成生存的不平等。然而，在NHB中，BMI并不能始终预测乳腺癌后的生存率 女性或女性激素受体阴性乳腺肿瘤，这在NHB女性中更常见。 初步研究表明，脂肪组织分布的更具体的措施优于BMI， 预测乳腺癌的存活率。考虑到在给定BMI下脂肪组织分布的种族差异， 需要研究身体成分，以阐明肥胖在产生种族差异中的作用。 这一行政补充建立了癌症差异专家和 研究团队拥有流行病学、肿瘤生物学和乳腺肿瘤医学方面的专业知识。家长补助金旨在 了解患者身体成分等全身因素如何影响局部乳腺肿瘤 微环境和乳腺癌存活率之间的关系。有了这个行政补充，我们扩大了那些 旨在通过比较NHB与NHW妇女来关注差异。我们将扩大代表性 NHB妇女的肿瘤，并进行了一系列的分析，重点是种族差异。 具体来说，我们将研究：内脏与皮下脂肪分布的种族差异， 这些脂肪组织库与生存率的关系（目标1）;每种脂肪组织库与生存率的关系的种族差异 乳腺肿瘤微环境中表达免疫和代谢基因的脂肪组织贮库 (Aim 2）;和免疫和代谢基因在乳腺TME中的关联的种族差异， 生存（目标3）。过度肥胖的潜在危害可以通过医疗和生活方式来减轻 因此，了解肥胖在乳腺癌中产生种族差异的作用是一个很高的目标。 不仅是研究，也是病人护理。

项目成果

Adipose tissue radiodensity and mortality among patients with nonmetastatic breast cancer.

• DOI: 10.1016/j.clnu.2022.09.016
• 发表时间: 2022-12
• 期刊: CLINICAL NUTRITION
• 影响因子: 6.3
• 作者: Cheng, En;Caan, Bette J.;Chen, Wendy Y.;Irwin, Melinda L.;Prado, Carla M.;Feliciano, Elizabeth M. Cespedes
• 通讯作者: Feliciano, Elizabeth M. Cespedes

Adiposity and cancer survival: a systematic review and meta-analysis.

• DOI: 10.1007/s10552-022-01613-7
• 发表时间: 2022-10
• 期刊: Cancer causes & control : CCC
• 作者: Cheng E;Kirley J;Cespedes Feliciano EM;Caan BJ
• 通讯作者: Caan BJ

Metabolic abnormalities and survival among patients with non-metastatic breast cancer.

• DOI: 10.1186/s12885-022-10430-9
• 发表时间: 2022-12-29
• 期刊: BMC cancer
• 影响因子: 3.8

Plant-Based Dietary Patterns and Breast Cancer Recurrence and Survival in the Pathways Study.

• DOI: 10.3390/nu13103374
• 发表时间: 2021-09-25
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: Anyene IC;Ergas IJ;Kwan ML;Roh JM;Ambrosone CB;Kushi LH;Cespedes Feliciano EM
• 通讯作者: Cespedes Feliciano EM

Diet Quality and Breast Cancer Recurrence and Survival: The Pathways Study.

• DOI: 10.1093/jncics/pkab019
• 发表时间: 2021-04
• 期刊: JNCI cancer spectrum
• 影响因子: 4.4
• 作者: Ergas IJ;Cespedes Feliciano EM;Bradshaw PT;Roh JM;Kwan ML;Cadenhead J;Santiago-Torres M;Troeschel AN;Laraia B;Madsen K;Kushi LH
• 通讯作者: Kushi LH