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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.
摘要：
在目前的研究中,我们评估了乳腺癌(ApoCa)中HER2低表型的患病率和分子特征及其与肿瘤浸润淋巴细胞(TIL)的关系.使用了64个充分表征的未治疗ApoCa的队列。根据国际TIL工作组的建议，使用苏木精和曙红整个幻灯片/扫描图像评估TIL分布。在HER2低ApoCa的子集中进行下一代测序(NGS)。所有患者都是女性,平均年龄62岁.43个癌是纯的大汗腺癌（PAC；ER-/AR），其余21例被归类为大分泌样癌(ALCs；ER+/-，AR+/-）。HER2/neu在20/43（47%）PAC和4/21（19%）ALC中呈阳性（IHC评分3+和/或FISH扩增）。ApoCa中HER2低表达(评分1+或2+无HER2扩增)的患病率为39%,PAC和ALC之间无显著差异(P=0.14);低HER2表型在三阴性PAC中比在ALC中更普遍(P<0.001).74%的ApoCa的TIL水平较低(≤10%)(中位数为5%，范围0%-50%)。ALC的TIL水平明显高于PAC（P=0.02）。HER2状态对TIL分布无影响(P=0.45)。HER2低ApoCa的基因组谱与ApoCa的其他亚型相似。ApoCa主要具有低TIL，尤其是PAC。ApoCa中HER2低表型的患病率很高，考虑到最近批准的抗体-药物缀合物（ADC）治疗HER2低乳腺癌的治疗方法，该方法应具有治疗和临床意义。
