The Association between Molecular Subtypes of Breast Cancer with Histological Grade and Lymph Node Metastases in Indonesian Woman

Objective: Breast carcinoma is a heterogeneous disease which is rich in diversity. Molecular subtypes of breast cancer, histological grade and lymph node metastases are strong prognostic and predictive factors. In Indonesia, only a limited number of studies have investigated the correlation between molecular subtypes with histological grade and lymph node metastases. Methods: We analyzed 247 invasive breast carcinoma cases from the Anatomic Pathology Installation of Dr. Sardjito General Hospital Yogyakarta between 2012-2015. The slides were stained for estrogen receptors (ER), progesterone receptors (PR), HER2, Ki-67 and CK5/6 for classification into breast cancer subtypes (BCS). Histological grade using the Nottingham system and lymph node status were obtained from anatomic pathology records. The association between histological grade and lymph node status with BCS was examined with Chi-square tests. Results: The immunohistochemical features of 247 cases of women with invasive breast carcinoma were examined. There were 102 (41.3%) patients with Luminal A, 34 (13.8%) patients with Luminal B, 48 (19.4%) patients with HER2-positive, and 63 (25.5%) patients with triple negative breast cancer (TNBC). There were 148 (59.9%) patients with negative lymph node status and 99 (40.1%) with positive status. Among 63 TNBC cases, 37 (58.7%) patients were positive for CK5/6 staining (basal-like). Statistically, there were significant differences between histological grade and subtypes (p=0.013). However, no significant differences were found for lymph node metastases (p=0.540). Conclusion: Among subtypes, Luminal A has the highest frequency, followed by TNBC, HER2-positive and Luminal B. Histological grade was associated with molecular subtypes of breast carcinoma in Yogyakarta. Grade I was associated with Luminal A, while Grade III was associated with Luminal B, HER2 and TNBC subtypes.