Proliferative epithelial changes in tumour adjacent tissue in Sri Lankan women with breast carcinoma: do morphological changes support molecular models of breast carcinogenesis?

BACKGROUND: The multistep molecular model of breast carcinogenesis is based on the oestrogen receptor(ER) status of the tumour. Its two main arms comprise ER-positive and ER-negative breast carcinomas(BCa), which are associated with Nottingham grade(NG) of the tumour and different proliferative epithelial changes. According to the model, columnar cell lesions(CCL), lobular carcinoma in-situ(LCIS) and atypical ductal hyperplasia(ADH), low-grade ductal carcinoma in-situ (LG-DCIS) are associated with low grade ER-positive tumours and microglandular adenosis (MGA), pleomorphic LCIS(PLCIS), high-grade DCIS(HG-DCIS) are associated with ER-negative high grade tumours. This study aims to describe the association between proliferative epithelial changes in breast tissue adjacent to tumour, in relation to the ER status and NG of the tumour. METHODS: This descriptive cross-sectional study included 420, wide local excision and mastectomy specimens of BCa from National Hospital of Sri Lanka, between 2017-2019. The histopathological features of the tumour and proliferative epithelial changes in tumour adjacent tissue within 10 mm distance from the tumour-host interface were evaluated independently by two pathologists. The ER, PR(Progesterone receptor) and HER2 status assessed by immunohistochemistry(IHC) was reviewed. The associations between above epithelial lesions and ER status and NG{categorised as low grade (NG1 and NG2) and high grade (NG3)} of the tumour were analyzed. RESULTS: ER positive BCa showed significant associations with CCH (p = 0.04), FEA (p = 0.035) and LGDCIS (p < 0.001). Although PLCIS was more frequent in ER positive tumours, the association did not attain statistical significance. ER negative BCa showed a significant association with HGDCIS (p = 0.016). CCLs as a whole (p = 0.005) and also CCC (p = 0.006) and FEA (p = 0.048) and LGDCIS (p < 0.001) showed significant associations with low NG tumours. High NG tumours showed a significant association with HGDCIS (p < 0.001). Microglandular adenosis was not identified in our study population. CONCLUSION: These morphological findings support the multistep molecular based pathogenetic pathways of breast carcinoma in the studied setting in South Asia. Identification of these proliferative epithelial components in a core biopsy that is negative for BCa, should prompt for close clinicoradiological correlation, and if necessary re-biopsy of women suspected of harbouring a BCa.

Androgen receptor expression in a Sri Lankan patient cohort with early breast carcinoma.

BACKGROUND: Androgen receptor (AR) expression is emerging as a prognostic biomarker in breast carcinoma (BCa). The study aimed to determine the prevalence of AR expression by immunohistochemical analysis among a cohort of Sri Lankan women with early BCa and to evaluate its association with clinicopathological features including immunohistochemical molecular subtype and early survival. METHOD: We studied the clinical and pathological features and immunohistochemical profile of 141 women undergoing primary surgery for early BCa, followed by standard adjuvant therapy. AR status was assessed by immunohistochemistry in all cases. Overall survival (OS) and disease-free survival (DFS) was determined. The relationship between AR expression and clinical and pathological parameters and immunohistochemical molecular subtype was analyzed using Student T test and chi-square tests. Cox regression analysis was used to analyze the prognostic impact of AR expression. RESULTS: AR expression was seen in 40.8%(95%CI 33.10-49.07%) of the BCa study cohort. None of the clinical data studied showed a significant association with the AR status(p > 0.05). Ductal carcinoma in situ(p = 0.003), oestrogen receptor (ER) (p = 0.001) and progesterone receptor (PR) (p = 0.001) positivity and luminal IHC molecular subtype(p = 0.016) were significantly associated with AR-positive status. AR-negative status was significantly associated with tumour necrosis > 50%(p = 0.031), moderate to extensive lymphocytic infiltrate at the tumour margin(p = 0.025) and basal triple negative breast carcinoma(p = 0.016). The mean duration of patient follow-up was 46.70(95% CI 46.495-46.905) months (3.89 years). On univariate analysis, AR-positivity was associated with better OS among ER-positive tumours(p = 0.047), specifically in postmenopausal women (p = 0.030). In ER-negative tumours, AR positivity was associated with worse DFS (p = 0.036). On multivariate analysis, TNM stage and ER/AR status were predictive of survival. ER-positive/AR-positive (ER+/AR+) tumours demonstrated better OS than ER-positive/AR-negative (ER+/AR-) tumours(p = 0.015). ER-negative/AR-positive (ER-/AR+) tumours (p = 0.014) had a worse DFS than ER-negative/AR-negative (ER-/AR-) tumours. CONCLUSIONS: AR prevalence obtained was low. AR positivity was associated with positivity for ER and PR. On multivariate analysis, apart from TNM stage only ER/AR status were predictive of OS and DFS, with concordant expression of ER/AR demonstrating a better, early survival.