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

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.

Figure 1.

(A) Hematoxylin and eosin stain of a case of PAC (ER−/AR+) of the breast with low TIL expression (∼1%), as indicated by black arrows (10x); The same case exhibited 2+ HER2 expression by immunohistochemistry (20x); (B) A subsequent FISH assay revealed no HER2/neu gene amplification (HER2/CEP17 ratio ═ 1.13). PAC: Pure apocrine carcinoma; TIL: Tumor-infiltrating lymphocyte; FISH: Fluorescent in situ hybridization.

Figure 2.

A case of apocrine-like (ER+/AR+) HER2-low (score 1+) carcinoma with moderate (∼50%) TIL expression (Hematoxylin and eosin, 10x). TIL: Tumor-infiltrating lymphocyte.