Mustapha Abubakar, Thomas U Ahearn, Maire A Duggan, Scott Lawrence, Ernest K Adjei, Joe-Nat Clegg-Lamptey, Joel Yarney, Beatrice Wiafe-Addai, Baffour Awuah, Seth Wiafe, Kofi Nyarko, Francis S Aitpillah, Daniel Ansong, Stephen M Hewitt, Louise A Brinton, Jonine D Figueroa, Montserrat Garcia-Closas, Lawrence Edusei, Nicolas Titiloye
{"title":"诊断前宿主因素对撒哈拉以南非洲妇女乳腺癌基质微环境形成的贡献。","authors":"Mustapha Abubakar, Thomas U Ahearn, Maire A Duggan, Scott Lawrence, Ernest K Adjei, Joe-Nat Clegg-Lamptey, Joel Yarney, Beatrice Wiafe-Addai, Baffour Awuah, Seth Wiafe, Kofi Nyarko, Francis S Aitpillah, Daniel Ansong, Stephen M Hewitt, Louise A Brinton, Jonine D Figueroa, Montserrat Garcia-Closas, Lawrence Edusei, Nicolas Titiloye","doi":"10.1158/1055-9965.EPI-24-0390","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The stromal microenvironment (SME) is integral to breast cancer biology, impacting metastatic proclivity and treatment response. Emerging data indicate that host factors may impact the SME, but the relationship between prediagnostic host factors and SME phenotype remains poorly characterized, particularly among women of African ancestry.</p><p><strong>Methods: </strong>We conducted a case-only analysis involving 792 patients with breast cancer (17-84 years) from the Ghana Breast Health Study. High-accuracy machine-learning algorithms were applied to standard H&E-stained images to characterize SME phenotypes [including percent tumor-associated connective tissue stroma, Ta-CTS (%); tumor-associated stromal cellular density, Ta-SCD (%)]. Associations between prediagnostic host factors and SME phenotypes were assessed in multivariable linear regression models.</p><p><strong>Results: </strong>Decreasing Ta-CTS and increasing Ta-SCD were associated with aggressive, mostly high-grade tumors (P-value < 0.001). Several prediagnostic host factors were associated with Ta-SCD independently of tumor characteristics. Compared with nulliparous women, parous women had higher levels of Ta-SCD [mean (standard deviation, SD) = 31.3% (7.6%) vs. 28.9% (7.1%); P-value = 0.01]. Similarly, women with a positive family history of breast cancer had higher levels of Ta-SCD than those without family history [mean (SD) = 33.0% (7.5%)] vs. 30.9% (7.6%); P-value = 0.03]. Conversely, increasing body size was associated with decreasing Ta-SCD [mean (SD) = 31.6% (7.4%), 31.4% (7.3%), and 30.1% (8.0%) for slight, average, and large body sizes, respectively; P-value = 0.005].</p><p><strong>Conclusions: </strong>Epidemiological risk factors were associated with varying degrees of stromal cellularity in tumors, independently of clinicopathological characteristics.</p><p><strong>Impact: </strong>The findings raise the possibility that epidemiological risk factors may partly influence tumor biology via the stromal microenvironment. See related In the Spotlight, p. 459.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":"462-473"},"PeriodicalIF":3.7000,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966112/pdf/","citationCount":"0","resultStr":"{\"title\":\"Contribution of Prediagnostic Host Factors to Shaping the Stromal Microenvironment of Breast Cancer among Sub-Saharan African Women.\",\"authors\":\"Mustapha Abubakar, Thomas U Ahearn, Maire A Duggan, Scott Lawrence, Ernest K Adjei, Joe-Nat Clegg-Lamptey, Joel Yarney, Beatrice Wiafe-Addai, Baffour Awuah, Seth Wiafe, Kofi Nyarko, Francis S Aitpillah, Daniel Ansong, Stephen M Hewitt, Louise A Brinton, Jonine D Figueroa, Montserrat Garcia-Closas, Lawrence Edusei, Nicolas Titiloye\",\"doi\":\"10.1158/1055-9965.EPI-24-0390\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The stromal microenvironment (SME) is integral to breast cancer biology, impacting metastatic proclivity and treatment response. Emerging data indicate that host factors may impact the SME, but the relationship between prediagnostic host factors and SME phenotype remains poorly characterized, particularly among women of African ancestry.</p><p><strong>Methods: </strong>We conducted a case-only analysis involving 792 patients with breast cancer (17-84 years) from the Ghana Breast Health Study. High-accuracy machine-learning algorithms were applied to standard H&E-stained images to characterize SME phenotypes [including percent tumor-associated connective tissue stroma, Ta-CTS (%); tumor-associated stromal cellular density, Ta-SCD (%)]. Associations between prediagnostic host factors and SME phenotypes were assessed in multivariable linear regression models.</p><p><strong>Results: </strong>Decreasing Ta-CTS and increasing Ta-SCD were associated with aggressive, mostly high-grade tumors (P-value < 0.001). Several prediagnostic host factors were associated with Ta-SCD independently of tumor characteristics. Compared with nulliparous women, parous women had higher levels of Ta-SCD [mean (standard deviation, SD) = 31.3% (7.6%) vs. 28.9% (7.1%); P-value = 0.01]. Similarly, women with a positive family history of breast cancer had higher levels of Ta-SCD than those without family history [mean (SD) = 33.0% (7.5%)] vs. 30.9% (7.6%); P-value = 0.03]. Conversely, increasing body size was associated with decreasing Ta-SCD [mean (SD) = 31.6% (7.4%), 31.4% (7.3%), and 30.1% (8.0%) for slight, average, and large body sizes, respectively; P-value = 0.005].</p><p><strong>Conclusions: </strong>Epidemiological risk factors were associated with varying degrees of stromal cellularity in tumors, independently of clinicopathological characteristics.</p><p><strong>Impact: </strong>The findings raise the possibility that epidemiological risk factors may partly influence tumor biology via the stromal microenvironment. See related In the Spotlight, p. 459.</p>\",\"PeriodicalId\":9458,\"journal\":{\"name\":\"Cancer Epidemiology Biomarkers & Prevention\",\"volume\":\" \",\"pages\":\"462-473\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-04-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966112/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Epidemiology Biomarkers & Prevention\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1055-9965.EPI-24-0390\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Epidemiology Biomarkers & Prevention","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1055-9965.EPI-24-0390","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：基质微环境（SME）是乳腺癌（BC）生物学不可或缺的组成部分，影响转移倾向和治疗反应。新出现的数据表明，宿主因素可能会对 SME 产生影响，但诊断前宿主因素与 SME 表型之间的关系尚不明确，尤其是在非洲裔女性中：我们对加纳乳腺健康研究（GBHS）中的 792 名 BC 患者（17-84 岁）进行了病例分析。高精度机器学习算法应用于标准 H&E 染色图像，以描述 SME 表型（包括肿瘤相关结缔组织基质百分比，Ta-CTS (%) 和肿瘤相关基质细胞密度，Ta-SCD (%)）。在多变量线性回归模型中评估了诊断前宿主因素与SME表型之间的关系：结果：Ta-CTS的降低和Ta-SCD的升高与侵袭性肿瘤（主要是高级别肿瘤）有关（p-value）：流行病学风险因素与肿瘤不同程度的基质细胞性相关，与临床病理学特征无关：影响：研究结果提出了一种可能性，即流行病学风险因素可能会通过 SME 对肿瘤生物学产生部分影响。
Contribution of Prediagnostic Host Factors to Shaping the Stromal Microenvironment of Breast Cancer among Sub-Saharan African Women.
Background: The stromal microenvironment (SME) is integral to breast cancer biology, impacting metastatic proclivity and treatment response. Emerging data indicate that host factors may impact the SME, but the relationship between prediagnostic host factors and SME phenotype remains poorly characterized, particularly among women of African ancestry.
Methods: We conducted a case-only analysis involving 792 patients with breast cancer (17-84 years) from the Ghana Breast Health Study. High-accuracy machine-learning algorithms were applied to standard H&E-stained images to characterize SME phenotypes [including percent tumor-associated connective tissue stroma, Ta-CTS (%); tumor-associated stromal cellular density, Ta-SCD (%)]. Associations between prediagnostic host factors and SME phenotypes were assessed in multivariable linear regression models.
Results: Decreasing Ta-CTS and increasing Ta-SCD were associated with aggressive, mostly high-grade tumors (P-value < 0.001). Several prediagnostic host factors were associated with Ta-SCD independently of tumor characteristics. Compared with nulliparous women, parous women had higher levels of Ta-SCD [mean (standard deviation, SD) = 31.3% (7.6%) vs. 28.9% (7.1%); P-value = 0.01]. Similarly, women with a positive family history of breast cancer had higher levels of Ta-SCD than those without family history [mean (SD) = 33.0% (7.5%)] vs. 30.9% (7.6%); P-value = 0.03]. Conversely, increasing body size was associated with decreasing Ta-SCD [mean (SD) = 31.6% (7.4%), 31.4% (7.3%), and 30.1% (8.0%) for slight, average, and large body sizes, respectively; P-value = 0.005].
Conclusions: Epidemiological risk factors were associated with varying degrees of stromal cellularity in tumors, independently of clinicopathological characteristics.
Impact: The findings raise the possibility that epidemiological risk factors may partly influence tumor biology via the stromal microenvironment. See related In the Spotlight, p. 459.
期刊介绍：
Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
