Immunohistochemistry-Based Molecular Subtype Distribution of Invasive Breast Cancer and Its Clinicopathological Correlates in a Bangladeshi Cohort
Abstract
Background/Context: Breast cancer is the second most common cancer worldwide, with approximately 2.3 million new cases annually. In Bangladesh, the disease predominantly affects premenopausal women and often presents at an advanced stage. The distribution of molecular subtypes which determine treatment strategies and prognosis has not been comprehensively characterized in large-scale single institution studies from Bangladesh.
Objective: To determine the prevalence and distribution of molecular subtypes of invasive breast carcinoma using immunohistochemical (IHC) surrogate markers according to St. Gallen criteria, and to evaluate their associations with clinicopathological parameters in a Bangladeshi cohort.
Materials and Methods: This cross-sectional observational study enrolled 107 consecutive patients with histopathologically confirmed invasive breast carcinoma at the Department of Pathology, TMSS Medical College, Bogura, Bangladesh, from January 2024 to December 2024. IHC was performed for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 using standardized protocols with ASCO/CAP guidelines for HER2 and the Allred scoring system for hormone receptors. Tumours were classified into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and triple-negative breast cancer (TNBC)) per St. Gallen subgroup definitions. Clinicopathological associations were assessed using chi-square or Fisher’s exact test (p < 0.05).
Results: The mean patient age was 45.4 ± 10.6 years, with 67.3% of patients in the 31–50 years age group. TNBC was the most prevalent subtype (33/107, 30.8%), followed by Luminal A (28/107, 26.2%), HER2-enriched (23/107, 21.5%), Luminal B (18/107, 16.8%) and Luminal B (HER2-positive) tumours (5/107, 4.7%). Statistically significant associations were identified between molecular subtype and histological grade (p = 0.004) and lymph node metastasis (p = 0.035). Grade III tumours were predominantly TNBC (52.2%), while Luminal A predominated in Grade I (50%). HER2 enriched subtype was the most frequent among cases with extensive nodal involvement (N3a, 60%).
Conclusions: This study reveals a distinctive molecular landscape of breast cancer in Bangladesh, characterised by a high prevalence of TNBC exceeding global rates. The significant associations between molecular subtypes and tumour grade and nodal status validate the St. Gallen IHC classification for clinical practice in resource-limited settings. These findings underscore the urgent need for robust chemotherapy infrastructure, access to HER2-targeted therapies, and enhanced early detection programmes. approximately 666,000 deaths (6.9% of global cancer
deaths) annually." Despite moderate improvements in
survival attributable to advances in carly detection and
systemic therapies, breast cancer continues to claim an
unacceptably high number of lives, owing largely to its
heterogeneous biological behaviour, variable treatment
responsiveness, and differential access to care
worldwide.
Keywords
Immunohistochemistry
Molecular subtypes
Triple-negative breast cancer
Estrogen receptor
HER2 protein
Ki-67 antigen
Bangladesh
Introduction
Breast cancer is the most prevalent malignancy among
women worldwide and represents a major global
health burden. According to GLOBOCAN 2022
estimates, female breast cancer is the second leading cause of cancer incidence globally, with approximately
2.3 million new cases accounting for 11.6% of ail
cancer diagnoses. The disease ranks fourth in
cancerrelated mortality, responsible for