Xinyi Qu¹, Noel Chia¹, Puay Hoon Tan^2,3, Wong Fuh Yong⁴, Phyu Nitar⁵, Mihir Gudi²

¹Department of Pathology, National University Hospital, Singapore 

²Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore 

³Luma Medical Centre, Royal Square Medical Centre, Singapore

⁴Division of Radiation Oncology, National Cancer Centre, Singapore 

⁵Department of Cancer Informatics, National Cancer Centre Singapore, Singapore 

 

Background: HER2-negative breast cancers comprise approximately 50% of breast cancers and include HER2-low, -ultra low and -null subcategories. These tumors showed good response to trastuzumab deruxtecan in the DESTINY-Breast04 trial and DESTINY-Breast06 data showed similar response in HER2-low and -ultra low groups. This study investigates the incidence of HER2-positive, -low, -ultra low and -null tumors and correlation with clinicopathologic parameters in Singapore.

 

Design: This retrospective cohort study included 7809 patients with invasive breast cancer and HER2 IHC and ISH results. The variables analyzed include 5-year overall survival, pCR, age, race, multifocality, histologic type, grade, stage, and hormone receptor, lymph node and metastasis status.

 

Results: 28.3% of the patients had HER2-low, 9.3% had HER2-ultra low, 35% had HER2-null and 27.3% had HER2-positive tumors. The HER2-negative groups more commonly showed special histologic type, lower grade and stage, positive hormone receptor, negative lymph nodes, lower metastasis rate and lower pCR rate. The overall survival was slightly higher for HER2-low and -ultra low tumors (p=0.001).

 

Conclusion: In Singapore, HER2-low and -ultra low tumors comprise 37.6% of breast cancers and have a more favorable 5-year overall survival than HER2-positive and -null tumors. Further investigation is needed to determine whether the HER2-negative subcategories are truly distinct.

 

Statement of contribution: The corresponding author contributed to the literature review, data interpretation and discussion sections of the paper.