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.

抽象的 R01CA251589“身体成分和乳腺癌生存：免疫和代谢”的补充 乳腺肿瘤的生物标志物”响应 PAR-22-114“支持癌症的行政补充剂 差异合作研究。”长期目标是减轻乳房不成比例的负担 通过了解关键的作用，了解非西班牙裔黑人 (NHB) 女性经历的癌症死亡率， 可改变的危险因素：过度肥胖。 临床前模型表明，过度肥胖会损害抗肿瘤免疫并改变代谢和细胞 促进癌症进展的增殖途径。鉴于肥胖症患病率明显较高（身体 NHB 与非西班牙裔白人 (NHW) 女性的质量指数 [BMI] >30-kg/m2）相比，肥胖被认为是 造成生存差异。然而，BMI 并不能始终如一地预测 NHB 乳腺癌患者的生存率 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，更具体的脂肪组织分布测量指标优于 BMI 预测乳腺癌的生存率。鉴于特定 BMI 下脂肪组织分布的种族差异，存在 需要研究身体成分，以阐明肥胖在产生种族差异中的作用。 该行政补充在癌症差异专家和癌症专家之间建立了新的合作 研究团队拥有流行病学、肿瘤生物学和乳腺肿瘤医学专业知识。家长补助金寻求 了解患者身体成分等全身因素如何影响局部乳腺肿瘤 微环境和乳腺癌的生存。通过此行政补充，我们扩大了这些 旨在通过比较 NHB 与 NHW 女性来关注差异。我们将扩大代表性 我们的研究中研究了来自 NHB 女性的肿瘤，并针对种族差异进行了一系列分析。 具体来说，我们将检查： 内脏脂肪与皮下脂肪分布的种族差异以及 这些脂肪组织库与生存的关联（目标 1）；每个协会的种族差异 乳腺肿瘤微环境中表达免疫和代谢基因的脂肪组织库 （目标 2）；乳腺 TME 中免疫和代谢基因关联的种族差异 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 干预措施；因此，了解肥胖在乳腺癌种族差异中的作用是一个非常重要的任务。 不仅优先考虑研究，而且优先考虑患者护理。

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