Contribution of Prediagnostic Host Factors to Shaping the Stromal Microenvironment of Breast Cancer among Sub-Saharan African Women.
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ICR Authors
Authors
Abubakar, M
Ahearn, TU
Duggan, MA
Lawrence, S
Adjei, EK
Clegg-Lamptey, J-N
Yarney, J
Wiafe-Addai, B
Awuah, B
Wiafe, S
Nyarko, K
Aitpillah, FS
Ansong, D
Hewitt, SM
Brinton, LA
Figueroa, JD
Garcia-Closas, M
Edusei, L
Titiloye, N
Ghana Breast Health Study Team,
Ahearn, TU
Duggan, MA
Lawrence, S
Adjei, EK
Clegg-Lamptey, J-N
Yarney, J
Wiafe-Addai, B
Awuah, B
Wiafe, S
Nyarko, K
Aitpillah, FS
Ansong, D
Hewitt, SM
Brinton, LA
Figueroa, JD
Garcia-Closas, M
Edusei, L
Titiloye, N
Ghana Breast Health Study Team,
Document Type
Journal Article
Date
2025-04-03
Date Accepted
2024-07-01
Abstract
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.
Citation
Cancer Epidemiology, Biomarkers and Prevention, 2024, pp. OF1 - OF12
Source Title
Cancer Epidemiology, Biomarkers and Prevention
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
1055-9965
eISSN
1538-7755
Collections
Research Team
Integrative Cancer Epidem