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All Journal Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research
Widyanti Soewoto
Department of Oncology Surgery, Faculty of Medicine, Universitas Sebelas Maret/Dr. Moewardi Regional General Hospital, Surakarta, Indonesia
Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology Neuroscience

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Intracrine Dynamics of Luminal Breast Cancer: Correlating Intratumoral Estradiol with Estrogen Receptor Alpha Overexpression in an Advanced-Stage Cohort Erdiansyah Reza Lesmana; Widyanti Soewoto; Brian Wasita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 3 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i3.1542

Abstract

Background: In postmenopausal breast cancer, systemic serum estradiol levels often fail to reflect the biologically active concentrations within the tumor microenvironment, a phenomenon known as intracrineology. While the roles of estrogen receptor alpha (ERα) and beta (ERβ) are well-characterized, the specific relationship between local ligand concentration and receptor expression in advanced-stage malignancies remains under-investigated. This study investigates the correlation between intratumoral estradiol (E2) concentration and the expression of ER isoforms in Luminal A and Luminal B subtypes. Methods: A retrospective cross-sectional study was conducted on 56 tissue samples (38 Luminal A, 18 Luminal B) from patients at Dr. Moewardi Regional General Hospital, Indonesia. Pre-analytical variables were strictly controlled, ensuring cold ischemia time was less than one hour. Expressions of E2, ERα, and ERβ were quantified using immunohistochemistry and assessed via H-Scores. Due to non-normal data distribution, associations were analyzed using Spearman’s Rho and Generalized Linear Models (GLM) with a Gamma distribution and log-link function, coupled with bootstrapping to generate robust confidence intervals. Results: The cohort was characterized by advanced disease, with 85.7% of patients presenting with Stage III or IV breast cancer. Luminal A tumors exhibited significantly higher mean intratumoral E2 (91.58 versus 56.67; p = 0.038) and ERα expression (122.23 versus 109.72; p = 0.045) compared to Luminal B. A significant positive correlation was observed between tissue E2 and ERα (Rho = 0.347; p = 0.009). GLM analysis confirmed E2 as a significant predictor of ERα expression (p = 0.015), independent of age and stage. No significant correlation was found between E2 and ERβ (p = 0.113). Conclusion: Intratumoral estradiol is a significant positive correlate of ERα expression in luminal breast cancer, supporting the existence of a ligand-driven autocrine maintenance loop even in advanced stages. The lack of correlation with ERβ suggests divergent regulatory mechanisms. These findings reinforce the rationale for therapies targeting local aromatase activity.
Intracrine Dynamics of Luminal Breast Cancer: Correlating Intratumoral Estradiol with Estrogen Receptor Alpha Overexpression in an Advanced-Stage Cohort Erdiansyah Reza Lesmana; Widyanti Soewoto; Brian Wasita
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 3 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i3.1542

Abstract

Background: In postmenopausal breast cancer, systemic serum estradiol levels often fail to reflect the biologically active concentrations within the tumor microenvironment, a phenomenon known as intracrineology. While the roles of estrogen receptor alpha (ERα) and beta (ERβ) are well-characterized, the specific relationship between local ligand concentration and receptor expression in advanced-stage malignancies remains under-investigated. This study investigates the correlation between intratumoral estradiol (E2) concentration and the expression of ER isoforms in Luminal A and Luminal B subtypes. Methods: A retrospective cross-sectional study was conducted on 56 tissue samples (38 Luminal A, 18 Luminal B) from patients at Dr. Moewardi Regional General Hospital, Indonesia. Pre-analytical variables were strictly controlled, ensuring cold ischemia time was less than one hour. Expressions of E2, ERα, and ERβ were quantified using immunohistochemistry and assessed via H-Scores. Due to non-normal data distribution, associations were analyzed using Spearman’s Rho and Generalized Linear Models (GLM) with a Gamma distribution and log-link function, coupled with bootstrapping to generate robust confidence intervals. Results: The cohort was characterized by advanced disease, with 85.7% of patients presenting with Stage III or IV breast cancer. Luminal A tumors exhibited significantly higher mean intratumoral E2 (91.58 versus 56.67; p = 0.038) and ERα expression (122.23 versus 109.72; p = 0.045) compared to Luminal B. A significant positive correlation was observed between tissue E2 and ERα (Rho = 0.347; p = 0.009). GLM analysis confirmed E2 as a significant predictor of ERα expression (p = 0.015), independent of age and stage. No significant correlation was found between E2 and ERβ (p = 0.113). Conclusion: Intratumoral estradiol is a significant positive correlate of ERα expression in luminal breast cancer, supporting the existence of a ligand-driven autocrine maintenance loop even in advanced stages. The lack of correlation with ERβ suggests divergent regulatory mechanisms. These findings reinforce the rationale for therapies targeting local aromatase activity.
Co-Authors Brian Wasita Erdiansyah Reza Lesmana