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

摘要 R01CA251589《身体成分与乳腺癌生存：免疫和代谢》的补充 乳腺癌中的生物标记物对PAR-22-114支持癌症的药物补充的反应 差异合作研究。长期目标是减轻不成比例的乳房负担 非西班牙裔黑人(NHB)女性经历的癌症死亡率通过了解关键因素的作用， 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。鉴于肥胖率明显较高(身体 体重指数[BMI]和30公斤/平方米)在NHB与非西班牙裔白人(NHW)女性中，肥胖被认为是 造成生存差距的因素。然而，体重指数并不能始终如一地预测NHB患者乳腺癌后的存活率 女性或女性激素受体阴性的乳腺肿瘤，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指标优于BMI 预测乳腺癌的存活率。考虑到特定体重指数下脂肪组织分布的种族差异， 需要研究身体成分，以阐明肥胖在造成种族差异中的作用。 这一行政副刊建立了癌症差异专家和 具有流行病学、肿瘤生物学和乳腺内科肿瘤学专业知识的研究团队。家长拨款寻求 了解患者身体成分等全身因素对局部乳腺肿瘤的影响 微环境对乳腺癌存活率的影响。通过此管理补充，我们扩展了 旨在通过比较NHB和NHW女性来关注差异。我们将扩大其代表权。 我们研究了来自NHB妇女的肿瘤，并进行了一系列侧重于种族差异的分析。 具体地说，我们将检查：内脏与皮下肥胖症分布的种族差异 这些脂肪组织储存库与存活率的关联(目标1)；每种关联的种族差异 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)；以及乳房TME中免疫和代谢基因的种族差异与 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缓解 干预；因此，了解肥胖症在造成乳腺癌种族差异中的作用是很高的 不仅是研究的重点，也是病人护理的优先事项。

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.