Analysis of terminal duct lobular unit involution in luminal, her-2enriched and triple negative breast cancer subtypes
Date of Award
Master of Medicine (MMed)
Dr. Shahin Sayed
Dr. Zahir Moloo
Dr. Rose Ndumia
Pathology (East Africa)
Introduction: The terminal duct lobular unit (TDLU) of the breast is the most common origin of most breast cancers (BC). With increasing age and menopause, physiologic involution of TDLU occurs with a reduction in both the number and size of the lobules. Reduced TDLU involution is associated with a higher mammographic breast density (MBD) which by itself is a strong breast cancer risk factor. Recent studies have shown that TDLU involution is associated with a reduced risk of breast cancer and involution also differs with molecular subtypes of BC.
Studies have shown that the etiology, pathogenesis and prognosis of the three main subtypes of breast cancer (Luminal, HER 2- Enriched and Triple Negative) are different but the understanding of the corresponding association with TDLU involution is limited particularly in non-European populations.
Objectives: The aim of this study was to compare TDLU involution variables between Luminal and Triple Negative subtypes of breast cancer and the association between TDLU involution variables with mammographic density and specific demographic data in an understudied African population.
Methodology: This was a retrospective laboratory based cross-sectional study conducted at the Pathology department of the Aga Khan University Hospital, Nairobi.
The study population included all women with pathologically confirmed Breast Cancer with accompanying definitive surgery specimens (lumpectomy/ mastectomy) and normal breast tissue blocks, diagnosed at the Pathology Department of the Aga Khan University Hospital, Nairobi between January 2012 and December 2019. Formalin fixed paraffin embedded (FFPE) blocks representing normal breast were retrieved from the archives and Hematoxylin and Eosin stained sections cut at 4um. Visual TDLU count was performed and both mean and highest TDLU counts were recorded per case. The mammographic breast density was also recorded based on the BI-RADS lexicon. v
Data Analysis: Patient and tumor characteristics were recorded as categorical data and summarized using frequencies and percentages.
Kruskall-Wallis test was used to determine if there was a statistical difference between the visual TDLU counts (mean and highest) across the three tumor subtypes and mammographic densities.
Multivariate analysis such as logistic regression models were used to identify associations between visual TDLU counts and patient and tumor characteristics.
Results: A total of 189 cases were selected for the study. TDLU count was shown to decrease with increasing age and BMI with the decline being more pronounced prior to age 50. TDLU count was also higher for pre-menopausal women compared to post-menopausal women. There was no association between mammographic density, ER, PR, HER-2 status, tumor grade or molecular subtype of breast cancer.
Conclusion: Our results show that TDLU counts are significantly associated with increasing age, menopause and increasing BMI but we found no association between TDLU count with molecular subtype of breast cancer and mammographic density.
With our analyses being limited by our sample size, we recommend a larger study with quantitative measures of TDLU involution and mammographic density to be conducted in future to further explore these associations of TDLU involution in relation to patient and tumor characteristics.
Kiwinga, J. N. (2020). Analysis of terminal duct lobular unit involution in luminal, her-2enriched and triple negative breast cancer subtypes (Unpublished master's dissertation). Aga Khan University, East Africa.