HER2 抗体药物偶联物现在可以靶向采用人表皮生长因子受体 2 (HER2) 免疫组织化学 (IHC) 1 或 2 阴性原位杂交 (ISH)（HER2-低）的乳腺癌。我们着手比较匹配的原发性浸润性乳腺癌 (IBC) 和远处转移 (DM) 之间的 HER2 状态与临床病理相关性，特别关注 HER2-low。原发性 IBC 诊断为匹配 DM 的生物标志物研究和临床病理特征对2021年至2022年期间的情况进行了回顾性分析。根据 2023 年美国临床肿瘤学会/美国病理学家学院 (ASCO/CAP) 的 IHC (4B5) 和 ISH (IQFISH pharmDX) 指南评估 HER2 状态。双侧乳房初选被排除。重新评估 HER2 IHC 0 至 1。鉴定出 147 例伴有匹配 DM 的原发性 IBC 病例。对核心活检（n = 74）和切除术（n = 73）进行生物标记。一百二十六 (86%) 最初被归类为“HER2 阴性”；其中，67 例 (46%) 被重新分类为 HER2 低。 HER2阳性原发患者年龄较小（P = 0.01），微乳头状癌的发生率较高（P = 0.02）。与 HER2 0 相比，HER2 低原代的微乳头状癌 (P = 0.02) 和雌激素受体 (ER) 阳性 (P = 0.02) 的发生率也有所增加。 确定了 169 例匹配的 DM 病例（排除骨转移）（范围= 每个 IBC 一到七个转移灶）。最常见的转移部位是肝脏（169 例中的 50 例，30%）、肺（169 例中的 36 例；21%）、远处淋巴结（169 例中的 26 例，15%）； 138 例 DM 病例 (82%) 先前被分类为“HER2 阴性”，62 例 (37%) 被重新分类为 HER2 低。与 HER2 低原发灶一样，HER2 低转移灶经常呈 ER 阳性（62 例中有 52 例；84%）（P = 0.02）。脑转移瘤更常见 HER2 阳性（32 例中有 5 例；16%）（P = 0.04）。比较匹配的初选和 DM 中的 HER2 状态，62 例 (37%) 的 HER2 状态不一致。大多数变化发生在从 HER2-low 到 HER2 0（169 例中有 33 例，占 20%）、HER2 0 到 HER2-low（169 例中有 17 例，占 10%）以及 HER2-low 到阳性（169 例中有 10 例，占 6%）。所有 HER2-low 至 HER2 0 的变化均为 HER2 1 至 0。在 30 例多发 DM 部位患者（47 例）中，不同 DM 样本间 HER2 状态不一致的患者有 16 例（53%），主要是从 HER2-low 至 HER2 0 （47 例中的 16 例，34%）。之前的“HER2 阴性”初选和 DM 病例中很大一部分被重新分类为 HER2 低。 IBC 原发灶和转移灶之间以及不同 DM 部位之间的 HER2 状态不一致，证明了肿瘤异质性，并强调了在远处转移中重新检测 HER2 的必要性。© 2024 John Wiley

Breast cancer with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+ or 2+ with negative in-situ hybridisation (ISH) (HER2-low) can now be targeted by HER2 antibody drug conjugates. We set out to compare HER2 status between matched primary invasive breast carcinoma (IBC) and distant metastases (DM) with clinical-pathological correlation, with specific interest in HER2-low.Biomarker studies and clinical-pathological features of primary IBC with matched DM diagnosed between 2021 and 2022 were retrospectively analysed. HER2 status was assessed per 2023 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for IHC (4B5) and ISH (IQFISH pharmDX). Bilateral breast primaries were excluded. HER2 IHC 0 to 1+ were reassessed.One hundred and forty-seven cases of primary IBC with matched DM were identified. Biomarkers were performed on core biopsy (n = 74) and resection (n = 73). One hundred and twenty-six (86%) were initially classified as 'HER2-negative'; of these, 67 (46%) were reclassified as HER2-low. Patients with HER2-positive primaries were younger (P = 0.01) and had an increased incidence of micropapillary carcinoma (P = 0.02). HER2-low primaries also had an increased incidence of micropapillary carcinoma (P = 0.02) and oestrogen receptor (ER) positivity (P = 0.02) compared to HER2 0. One hundred and sixty-nine matched DM cases excluding bone metastasis were identified (range = one to seven metastases per IBC). The most common sites of metastases were liver (50 of 169, 30%), lung (36 of 169; 21%), distant lymph node (26 of 169, 15%); 138 DM cases (82%) were previously classified as 'HER2-negative', and 62 (37%) were reclassified as HER2-low. Like HER2-low primaries, HER2-low metastases were frequently ER-positive (52 of 62; 84%) (P = 0.02). Brain metastases were more frequently HER2-positive (five of 32; 16%) (P = 0.04). Comparing HER2 status in matched primaries and DM, HER2 status was discordant in 62 cases (37%). Most changes occurred from HER2-low to HER2 0 (33 of 169, 20%), HER2 0 to HER2-low (17 of 169, 10%) and HER2-low to positive (10 of 169, 6%). All HER2-low to HER2 0 changes were HER2 1+ to 0. In 30 patients with multiple DM sites (47 cases), HER2 status among different DM samples was discordant in 16 patients (53%), mainly from HER2-low to HER2 0 (16 of 47, 34%).A significant proportion of previous 'HER2-negative' primaries and DM cases were reclassified as HER2-low. Discordant HER2 status between IBC primary and metastasis and between different DM sites demonstrated tumour heterogeneity and highlights the need for HER2 retesting in distant metastasis.© 2024 John Wiley & Sons Ltd.