Predictive Value of Excision Repair Cross Complementation Group 1 (ERCC1) by Immunohistochemistry for Determining Neoadjuvant Chemotherapy Response in Triple‐Negative Breast Cancers
Authors: Hashmi Atif Ali , Ajaz Yumna , Sajjad Muhsana , Zia Fazail , Irfan Muhammad , Abu Bakar Syed Muhammad , Khan Erum Yousuf , Faridi Naveen 
Published: February 2025

Introduction: Triple‐negative breast cancers (TNBCs) constitute a significant proportion of breast cancers in Pakistan. Owing to the lack of expression of hormone (estrogen/progesterone) receptor and human epidermal growth factor receptor 2 (HER2neu), treatment options for TNBCs are limited. Therefore, it is important to identify markers that predict response to chemotherapy in these patients. Previous studies have demonstrated that the excision repair cross complementation group 1 (ERCC1) protein can successfully augur the response to chemotherapy in cancer; however, data related to TNBCs, particularly in Pakistan, are limited. Therefore, in this study, we evaluated the role of ERCC1 in predicting the response to neoadjuvant chemotherapy in patients with TNBCs.

Methods: This cross‐sectional study was conducted at the Liaquat National Hospital, Histopathology Department, between January 2019 and June 2023. A total of 132 biopsy‐proven cases of breast cancer that were negative for estrogen receptor (ER), progesterone receptor (PR), and HER/2neu and were administered neoadjuvant chemotherapy before surgery were included in the study. ERCC1 immunohistochemical (IHC) staining was performed on prechemotherapy needle biopsies. The results were scored semiquantitatively by assessing the average intensity on a scale of 0–3 (0, no staining; 1, weak nuclear staining; 2, intermediate nuclear staining; and 3, strong nuclear staining) and the proportion of tumor cells showing positive nuclear staining. The intensity and proportion scores were then multiplied to give a score that was divided by 100 to give an overall score, and scores equal to or higher than 1.0 were considered positive. Neoadjuvant chemotherapy response was categorized as pathological complete response (pCR) when no residual invasive breast carcinoma was found on the postneoadjuvant chemotherapy excision specimen and as pathological partial response (pPR) when residual cancer cells were present in admixed chemotherapy‐related changes. The residual cancer burden (RCB) was calculated using the MD Anderson RCB calculator. The association between ERCC1 expression and the chemotherapy response/RCB class was determined.

Results: We found that 90.9% (n = 120) of TNBC cases expressed ERCC1, whereas pCR was noted in 24 (18.2%) cases. A significant association was observed between ERCC1 expression and pCR. Cases with negative ERCC1 expression had a significantly higher frequency of pCR (66.7%) than those with positive ERCC1 expression (13.3%). Additionally, the ERCC1‐positive group showed a higher frequency of RCB classes II (36.7%) and III (43.3%) than the ERCC1‐negative group (RCB II: 25%; RCB III: 0%). Moreover, positive ERCC1 expression was associated with higher nodal (N) stage.

Conclusion: In this study, we established the role of negative ERCC1 expression in predicting the response to chemotherapy in neoadjuvant TNBC. Therefore, ERCC1 can be used as a predictive marker to stratify patients who will benefit from neoadjuvant therapy. Moreover, we also noted an association between ERCC1 expression and nodal metastasis; however, more large‐scale studies are needed to establish its role as a prognostic biomarker in TNBC.