Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience
Ga-Jing Kee, Ryan Ying-Cong Tan, Sultana Rehena, Joycelyn Jie-Xin Lee, Ma Wai-Wai Zaw, Wei-Xiang Lian, Joe Yeong, Su-Ming Tan, Swee-Ho Lim, Benita Kiat-Tee Tan, Yoon-Sim Yap, Rebecca Alexandra Dent, Fuh-Yong Wong, Guek-Eng Lee
Ga-Jing Kee, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Ryan Ying-Cong Tan, Joycelyn Jie-Xin Lee, Yoon-Sim Yap, Rebecca Alexandra Dent, Guek-Eng Lee, Division of Medical Oncology, National Cancer Centre, Singapore 169610, Singapore
Sultana Rehena, Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857, Singapore
Ma Wai-Wai Zaw, Department of Anaesthesiology, Singapore General Hospital, Singapore 169608, Singapore
Wei-Xiang Lian, Fuh-Yong Wong, Division of Radiation Oncology, National Cancer Centre, Singapore 169610, Singapore
Joe Yeong, Division of Pathology, Singapore General Hospital, Singapore 169608, Singapore
Su-Ming Tan, Division of Breast Surgery, Changi General Hospital, Singapore, 529889, Singapore
Su-Ming Tan, Swee-Ho Lim, Benita Kiat-Tee Tan, SingHealth Duke-NUS Breast Centre, Singapore 169610, Singapore
Swee-Ho Lim, Kandang Kerbau Breast Centre, Kandang Kerbau Women’s and Children’s Hospital, Singapore 229899, Singapore
Benita Kiat-Tee Tan, Department of Breast Surgery, Singapore General Hospital, Singapore 169608, Singapore
Author contributions: Kee GJ and Tan RYC designed research and wrote the paper; Zaw MWW, Kee GJ and Tan RYC collected data; Sultana R analyzed data; Lee JXJ, Lian WX, Yeong J, Tan SM, Lim SH, Tan BKT, Yap YS, Dent RA, Wong FH and Lee GE provided feedback on the paper.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Reviewer (IRB 2019/2419).
Informed consent statement: Informed consent was not required by the International Review Board (IRB 2019/2419) as our study did not require collection of personal/identifiable data from subjects or investigators.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at ryan.shea.tan.y.c@singhealth.com.sg.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ryan Ying-Cong Tan, MBBS, MRCP, Attending Doctor, Medical Oncologist, Division of Medical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore. ryan.shea.tan.y.c@singhealth.com.sg
Received: December 31, 2019
Peer-review started: December 31, 2019
First decision: March 15, 2020
Revised: April 16, 2020
Accepted: May 16, 2020
Article in press: May 16, 2020
Published online: May 24, 2020
ARTICLE HIGHLIGHTS
Research background
Invasive lobular carcinomas (ILC) represent about 5%-10% of breast cancer. Prevalence of overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer has been reported at 4.8%-5.1%. The clinicopathological characteristics of HER2 positive (HER2+) invasive ductal carcinomas are known to differ from that of HER2 negative (HER2-) invasive ductal carcinomas. However, there remains a paucity of research examining the characteristics of HER2+ as opposed to HER2- ILC, particularly in Asian populations.
Research motivation
This study compares the clinicopathological characteristics of HER2+ and HER2- ILC to assess the differences in survival probability between the two groups.
Research objectives
This study aims to investigate the prevalence and prognostic clinicopathological factors of HER2+ ILC in an Asian population.
Research methods
A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted. Demographic and clinical data were collected from medical records. We examined clinicopathological characteristics and survival in relation to HER2 status. Differences between HER2+ and HER2- ILC were tested using chi-squared test for categorical variables and Mann-Whitney U test for continuous variables. Overall survival (OS), disease-free survival (DFS) and breast cancer-specific overall survival (BCSS) were analyzed for HER2+ and HER2- status using Kaplan-Meier survival analysis and were tested using log-rank test. All statistical tests were two-sided and P < 0.05 was considered statistically significant.
Research results
Interestingly, although most ILC patients have HER2- tumours, our cohort reports a higher prevalence of HER2+ ILC (10.1%) as compared to some previous studies. The median survival time was 2.95 (interquartile range: 1.89-8.87) years and 4.16 (interquartile range: 1.84-8.32) years respectively for HER2+ and HER2- ILC patients (P = 0.315). Based on the multivariate analysis, significant negative prognostic factors were HER2+, age, ethnicity and Stage. HER2+ and Luminal B molecular subtypes also had also notably poorer OS compared to Luminal A subtype. Additional univariate and multivariate Cox proportional hazard regression analyses of BCSS and DFS demonstrated that HER2 positivity remained a significant negative prognostic factor for BCSS and DFS on both the univariate and multivariate analysis.
Research conclusions
In conclusion, our study demonstrates the prevalence of HER2+ ILC to be 10.1%. HER2+ ILC patients were more likely to have poorer prognostic features such as estrogen receptor negativity, progesterone receptor negativity and higher tumour grade. Lastly, patients with HER2+ ILC had poorer OS, BCSS and DFS compared to those with HER2- ILC.
Research perspectives
The findings from our study warrant further prospective studies to validate observation and investigate the benefit of various treatment modalities to improve outcomes in HER2+ ILC.
