Contribution of Prediagnostic Host Factors to Shaping the Stromal Microenvironment of Breast Cancer among Sub-Saharan African Women.

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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,

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

Research Team

Integrative Cancer Epidem

Notes