Predictive Value of Excision Repair Cross Complementation Group 1 (ERCC1) by Immunohistochemistry for Determining Neoadjuvant Chemotherapy Response in Triple-Negative Breast Cancers

IF 1.9 4区 医学 Q3 OBSTETRICS & GYNECOLOGY
Breast Journal Pub Date : 2025-02-17 DOI:10.1155/tbj/8410670
Atif Ali Hashmi, Yumna Ajaz, Muhsana Sajjad, Fazail Zia, Muhammad Irfan, Syed Muhammad Abu Bakar, Erum Yousuf Khan, Naveen Faridi
{"title":"Predictive Value of Excision Repair Cross Complementation Group 1 (ERCC1) by Immunohistochemistry for Determining Neoadjuvant Chemotherapy Response in Triple-Negative Breast Cancers","authors":"Atif Ali Hashmi,&nbsp;Yumna Ajaz,&nbsp;Muhsana Sajjad,&nbsp;Fazail Zia,&nbsp;Muhammad Irfan,&nbsp;Syed Muhammad Abu Bakar,&nbsp;Erum Yousuf Khan,&nbsp;Naveen Faridi","doi":"10.1155/tbj/8410670","DOIUrl":null,"url":null,"abstract":"<div>\n <p><b>Introduction:</b> 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.</p>\n <p><b>Methods:</b> 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.</p>\n <p><b>Results:</b> We found that 90.9% (<i>n</i> = 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.</p>\n <p><b>Conclusion:</b> 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.</p>\n </div>","PeriodicalId":56326,"journal":{"name":"Breast Journal","volume":"2025 1","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/tbj/8410670","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Journal","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/tbj/8410670","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

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.

Abstract Image

免疫组织化学检测切除修复交叉互补组1 (ERCC1)对三阴性乳腺癌新辅助化疗反应的预测价值
简介:三阴性乳腺癌(tnbc)在巴基斯坦的乳腺癌中占很大比例。由于缺乏激素(雌激素/孕酮)受体和人表皮生长因子受体2 (HER2neu)的表达,tnbc的治疗选择有限。因此,确定预测这些患者化疗反应的标志物是很重要的。先前的研究表明,切除修复交叉互补组1 (ERCC1)蛋白可以成功地预示癌症对化疗的反应;但是,有关tnbc的数据,特别是在巴基斯坦,是有限的。因此,在本研究中,我们评估了ERCC1在预测tnbc患者对新辅助化疗反应中的作用。方法:本横断面研究于2019年1月至2023年6月在Liaquat国家医院组织病理学部进行。本研究共纳入132例活检证实的乳腺癌患者,均为雌激素受体(ER)、孕激素受体(PR)、HER/2neu阴性,术前接受新辅助化疗。化疗前穿刺活检行ERCC1免疫组化(IHC)染色。对结果进行半定量评分,以0 - 3分评定平均强度(0,不染色;1、弱核染色;2、中间核染色;(3)强核染色)和核染色阳性的肿瘤细胞比例。然后将强度分数和比例分数相乘得到一个分数,除以100得到总分,分数等于或大于1.0被认为是积极的。当新辅助化疗切除标本上未发现浸润性乳腺癌残留时,新辅助化疗反应被归类为病理完全缓解(pCR),当混合化疗相关改变中存在残留癌细胞时,被归类为病理部分缓解(pPR)。残余癌负担(RCB)采用MD Anderson RCB计算器计算。确定了ERCC1表达与化疗反应/RCB分类之间的关系。结果:我们发现90.9% (n = 120)的TNBC病例表达ERCC1,而pCR在24例(18.2%)的TNBC病例中检测到。ERCC1表达与pCR之间存在显著相关性。ERCC1阴性表达组的pCR频率(66.7%)明显高于ERCC1阳性表达组(13.3%)。此外,ercc1阳性组出现RCB II类(36.7%)和III类(43.3%)的频率高于ercc1阴性组(RCB II: 25%;RCB iii: 0%)。此外,ERCC1阳性表达与较高的淋巴结(N)分期相关。结论:在本研究中,我们建立了ERCC1阴性表达在预测新辅助TNBC化疗反应中的作用。因此,ERCC1可以作为一种预测指标,对新辅助治疗中受益的患者进行分层。此外,我们还注意到ERCC1表达与淋巴结转移之间的关联;然而,需要更多的大规模研究来确定其作为TNBC预后生物标志物的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Breast Journal
Breast Journal 医学-妇产科学
CiteScore
4.00
自引率
0.00%
发文量
47
审稿时长
4-8 weeks
期刊介绍: The Breast Journal is the first comprehensive, multidisciplinary source devoted exclusively to all facets of research, diagnosis, and treatment of breast disease. The Breast Journal encompasses the latest news and technologies from the many medical specialties concerned with breast disease care in order to address the disease within the context of an integrated breast health care. This editorial philosophy recognizes the special social, sexual, and psychological considerations that distinguish cancer, and breast cancer in particular, from other serious diseases. Topics specifically within the scope of The Breast Journal include: Risk Factors Prevention Early Detection Diagnosis and Therapy Psychological Issues Quality of Life Biology of Breast Cancer.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信