Triple-Negative Metaplastic Breast Carcinoma: Association of Epidermal Growth Factor Receptor Expression With Prognostic Parameters and Clinical Outcome

Abstract

IntroductionMetaplastic breast carcinoma (MBC) is one of the rare special subtypes of breast carcinoma associated with poor prognostic features compared with invasive ductal carcinoma. Moreover, therapeutic options are limited in MBC owing to frequent triple-negative profiles of these tumors. Epidermal growth factor receptor (EGFR) is a proto-oncogene that is overexpressed in many human cancers, and is a potential therapeutic target. Therefore, in this study, we evaluated the expression of EGFR in MBC by immunohistochemistry, and its association with clinicopathological and prognostic parameters. MethodsWe conducted a retrospective observational study in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, over a period of seven years. A total of 61 cases with a histopathological diagnosis of MBC were included in the study. All slides were reviewed by histopathologists for diagnostic confirmation. Histopathological parameters, such as tumor size, grade, and nodal metastasis, were recorded. The representative tissue blocks were also retrieved and immunohistochemical studies were performed for cytokeratin 5/6 (CK5/6), Ki67, and EGFR. ResultsThe mean age of the patients was 44.48 ± 13.01 years. The mean tumor size was 5.72 ± 2.72 cm, with most of the cases belonging to tumor (T)-stage T3. Axillary metastasis was present in 57.4% cases, and the perinodal extension was present in 11.5% cases. Most tumors were grade III (85.2%), with a mean Ki67 index of 39.67% ± 20.38%. Most of the cases were nonbasal (83.6%), owing to the absent CK5/6 expression. Tumor recurrence was noted in 14.8% cases, with a median follow-up of 43 (13-83) months and median disease-free survival of 36 (12-60) months. Positive EGFR expression was noted in 52.5% cases. A significant association of EGFR expression was noted with tumor grade, mean Ki67 index, axillary metastasis, and nodal (N)-stage. Cases with positive EGFR expression were found to have higher grade (grade III), with higher Ki67 index, higher frequency of axillary metastasis, and higher N-stage. Moreover, cases with positive EGFR expression had lower disease-free survival compared to cases with negative EGFR expression. ConclusionWe found that a significant proportion of triple-negative MBC expressed EGFR. Moreover, EGFR overexpression was associated with poor pathological parameters and lower disease-free survival. Therefore, EGFR can be considered a potential prognostic biomarker and therapeutic target in triple-negative MBC; however, the correlation between gene amplification and protein overexpression is required to better uncover the role of EGFR as a therapeutic target.

Epidermal Growth Factor Receptor Overexpression in Triple Negative Breast Cancer

“…These results were similar to our research hence EGFR overexpression can be used as a prognostic tool to predict the invasive nature of the tumor which can lead to poor prognosis. 12 Contrary to the high expression of EGFR in our study another regional study concluded that EGFR overexpression was observed in only 2.7% of the cases with TNBC which may be due to underlying genetic alterations. 13 In our study the mean age of the patients diagnosed with TNBC was 46.27 ± 3.75 years as compared to 46.26 ± 12.22 years in an observational study conducted in Pakistan.…”

Mutant Phenotype p53 Immunohistochemical Expression Is Associated With Poor Prognostic Parameters and Disease-Free Survival in Triple-Negative Metaplastic Breast Carcinoma

“…Hematoxylin and eosin (H&E)-stained slides of all cases were retrieved and diagnoses were reviewed. Moreover, ER, PR and HER2/neu immunohistochemical studies were performed to confirm the triple-negative status, as described in previous studies [6][7][8][9][10]. Cytokeratin 5/6 (CK5/6) was performed to subtype triple-negative MBCs into basal and non-basal subtypes.…”