Correlation of RANK and RANKL with mammographic density in primary breast cancer patients

• Published in: Archives of gynecology and obstetrics Vol. 310; no. 2; pp. 1223 - 1233
• Main Authors: Wunderle, Marius, Heindl, Felix, Behrens, Annika S., Häberle, Lothar, Hack, Carolin C., Heusinger, Katharina, Huebner, Hanna, Gass, Paul, Ruebner, Matthias, Schulz-Wendtland, Rüdiger, Erber, Ramona, Hartmann, Arndt, Beckmann, Matthias W., Dougall, William C., Press, Michael F., Fasching, Peter A., Emons, Julius
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2024; Springer Nature B.V
• Subjects: Adult; Aged; Breast - diagnostic imaging; Breast - metabolism; Breast - pathology; Breast cancer; Breast Density; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Case-Control Studies; Endocrinology; Female; Gynecologic Oncology; Gynecology; Human Genetics; Humans; Immunohistochemistry; Medicine; Medicine & Public Health; Middle Aged; Obstetrics/Perinatology/Midwifery; RANK Ligand - analysis; RANK Ligand - metabolism; Receptor Activator of Nuclear Factor-kappa B - metabolism; Tissue Array Analysis; Tumors; Immunohistochemistry; Mammographic density; Breast cancer; RANKL expression; RANK expression
• ISSN: 1432-0711; 0932-0067; 1432-0711
• DOI: 10.1007/s00404-024-07495-1

Purpose
The receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) have been shown to promote proliferation of the breast and breast carcinogenesis. The objective of this analysis was to investigate whether tumor-specific RANK and RANKL expression in patients with primary breast cancer is associated with high percentage mammographic density (PMD), which is a known breast cancer risk factor.
Methods
Immunohistochemical staining of RANK and RANKL was performed in tissue microarrays (TMAs) from primary breast cancer samples of the Bavarian Breast Cancer Cases and Controls (BBCC) study. For RANK and RANKL expression, histochemical scores (H scores) with a cut-off value of > 0 vs 0 were established. PMD was measured in the contralateral, non-diseased breast. Linear regression models with PMD as outcome were calculated using common predictors of PMD (age at breast cancer diagnosis, body mass index (BMI) and parity) and RANK and RANKL H scores. Additionally, Spearman rank correlations (ρ) between PMD and RANK and RANKL H score were performed.
Results
In the final cohort of 412 patients, breast cancer-specific RANK and RANKL expression was not associated with PMD (
P
 = 0.68). There was no correlation between PMD and RANK H score (Spearman’s ρ = 0.01,
P
 = 0.87) or RANKL H score (Spearman’s ρ = 0.04,
P
 = 0.41). RANK expression was highest in triple-negative tumors, followed by HER2-positive, luminal B-like and luminal A-like tumors, while no subtype-specific expression of RANKL was found.
Conclusion
Results do not provide evidence for an association of RANK and RANKL expression in primary breast cancer with PMD.