New research on TILs and HER2 status in apocrine breast cancer published in Biomolecules and Biomedicine

‍As published in Biomolecules and Biomedicine Vol. 24 No. 2 (2024)

The assessment of tumor-infiltrating lymphocytes in invasive apocrine carcinoma of the breast in relation to the HER2 status

• Zoran Gatalica Reference Medicine, Phoenix, Arizona, USA; The University of Oklahoma Health Sciences Center, Oklahoma, USA
• Nataliya Kuzmova Reference Medicine, Phoenix, Arizona, USA https://orcid.org/0009-0009-9357-6239
• Inga Rose Reference Medicine, Phoenix, Arizona, USA https://orcid.org/0009-0003-7447-8007
• Monika Ulamec Ljudevit Jurak Clinical Department of Pathology and Cytology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia; Department of Pathology and Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb, Croatia https://orcid.org/0000-0002-4843-8154
• Melita Peric-Balja Oncological Pathology Department, Ljudevit Jurak Clinical Department of Pathology and Cytology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia https://orcid.org/0000-0002-4871-9677
• Faruk Skenderi Department of Pathology, Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina
• Semir Vranic College of Medicine, QU Health, Qatar University, Doha, Qatar

Abstract

In the current study, we assessed the prevalence and molecular features of HER2-low phenotype in the apocrine carcinomas of the breast (ApoCa) and its relationship with tumor-infiltrating lymphocytes (TILs). A cohort of 64 well-characterized therapy-naïve ApoCa was used. The TIL distribution was assessed using the hematoxylin and eosin whole slide/scanned images following the international TILs working group recommendations. Next-generation sequencing (NGS) was performed in a subset of HER2-low ApoCa. All patients were women, with a mean age of 62 years. Forty-three carcinomas were pure apocrine carcinoma (PAC; ER−/AR+), and the remaining 21 were classified as apocrine-like carcinomas (ALCs; ER+/−, AR+/−). HER2/neu was positive (score 3+ by IHC and/or amplified by FISH) in 20/43 (47%) PAC and 4/21 (19%) ALC. The prevalence of HER2-low expression (scores 1+ or 2+ without HER2 amplification) in ApoCa was 39% without significant differences between PAC and ALC (P = 0.14); however, the HER2-low phenotype was more prevalent in triple-negative PAC than in ALC (P < 0.001). Levels of TILs were low (≤10%) in 74% of ApoCa (median 5%, range 0%–50%). TIL levels were significantly higher in ALC than in PAC (P = 0.02). HER2 status had no impact on TIL distribution (P = 0.45). The genomic profile of HER2-low ApoCa was similar to other subtypes of ApoCa. ApoCa has predominantly low TIL, particularly PAC. The prevalence of the HER2-low phenotype in ApoCa is high, which should have therapeutic and clinical implications given the recently approved therapies with antibody–drug conjugates (ADCs) for HER2-low breast cancers.

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