HER2 Low Expression in Primary Male Breast Cancer

Katleen Nobbe; Melanie Erices-Leclercq; Frank Foerster; Robert Förster; Stephan E Baldus; Christian Rudlowski; Lars Schröder; Sabine Lubig

doi:10.2147/BCTT.S450682

HER2 Low Expression in Primary Male Breast Cancer

Breast Cancer (Dove Med Press). 2024 Mar 28:16:141-148. doi: 10.2147/BCTT.S450682. eCollection 2024.

Authors

Katleen Nobbe¹, Melanie Erices-Leclercq¹, Frank Foerster^{2

3}, Robert Förster⁴, Stephan E Baldus⁵, Christian Rudlowski^{1

6}, Lars Schröder⁷, Sabine Lubig¹

Affiliations

¹ Breast Unit, Lutheran Hospital Bergisch Gladbach, Bergisch Gladbach, Germany.
² Department of Economical Sciences, University of Applied Sciences, Zwickau, Germany.
³ Outpatient Department of Gynaecological Oncology and Palliative Care, Chemnitz, Germany.
⁴ Institute for Radiation Oncology, Cantonal Hospital Winterthur, Winterthur, Switzerland.
⁵ Institute for Pathology, Cytology and Molecular Pathology, Bergisch Gladbach, Germany.
⁶ Department of Gynecology, University Hospital Bonn, Bonn, Germany.
⁷ Department of Gynaecology and Obstetrics, Ketteler Krankenhaus, Offenbach, Germany.

Abstract

Purpose: The introduction of HER2-targeting antibody drug conjugates (ADCs) offers new treatment options for female breast cancer patients (FBC) expressing low levels of HER2 (HER2 low). No evidence was found that HER2 low describes a new FBC subtype. There is a lack of studies determining the impact of HER2 low in male breast cancer (MBC). In this study, we evaluate the prevalence of HER2 low in primary MBC and correlate the results with patient characteristics.

Patients and methods: In this study, histological specimens were obtained from 120 male patients diagnosed and treated for primary invasive breast cancer from 1995 to 2022 at Breast Cancer Units in Bergisch Gladbach, Chemnitz, and Zwickau, Germany. HER2 immunostaining and in situ hybridization were performed by central pathology and evaluated based on the ASCO/CAP guidelines. The correlation of expression of HER2 low with tumor biological characteristics and patient outcomes was investigated.

Results: Out of all cases, four patients (3.3%) showed HER2 positivity (3+), 39 (32.5%) patients were classified as HER2 low, 7 (5.8%) were HER2 2+ (no amplification), 32 (26.7%) were HER2 1+, and 77 (64.2%) were classified as HER2 zero. Out of 77 HER2 zero cases, 47 tumors (61.0%) showed incomplete staining, with <10% of tumor cells classified as HER2 ultralow. No statistical correlation between HER2 low and tumor biological characteristics and patients' survival was found.

Conclusion: Our findings show a notable, albeit lower, prevalence of HER2 low expression in primary MBC. However, tumors expressing HER2 low do not show specific tumor biological features to define a new breast cancer subtype in MBC. Our results suggest that a significant number of MBC patients could benefit from ADCs, as shown in FBC. Further studies are required to better understand HER2 low breast cancer, both generally and in MBC.

Keywords: HER2 low; male breast cancer; prognosis; survival.

Grants and funding

This work was supported by the German Cancer Foundation Grant Number 70-3157. The authors declare that no other support was received during the preparation of this article.