Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy; Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy.
Unit of Population Epidemiology, Division and Department of Primary Care Medicine, 1205 Geneva University Hospitals, Geneva, Switzerland; Department of Oncology, Geneva University Hospitals, 1205 Geneva, Switzerland.
Eur J Cancer. 2023 May;185:119-130. doi: 10.1016/j.ejca.2023.02.028. Epub 2023 Mar 8.
Invasive lobular carcinoma (ILC) has unique clinical-biological features. Phenotypical differences between primary tumours (PTs) and metastases (M) have been described for invasive ductal carcinoma, but data on ILC are limited.
We retrospectively analysed patients with recurrent ILC from our institution from 2013 to 2020. We evaluated the discordance of the oestrogen receptor (ER), progesterone receptor (PgR) and HER2 between PT and M, to understand prognostic and therapeutic implications.
Thirteen percent (n = 91) of all patients had ILC. We observed 15%, 44% and 5% of ER, PgR and HER2 status discordance between PT and M. ER/PgR discordance was related to receptor loss and HER2 mainly due to gain. PT presented a luminal-like phenotype (93%); 6% and 1% were triple-negative (TNBC) and HER2-positive. In M, there was an increase in TNBC (16%) and HER2-positive (5%). Metastasis-free survival and overall survival (OS) were different according to clinical phenotype, with poorer prognosis for HER2+ and TNBC (p < 0.001); OS after metastatic progression did not differ across phenotypes (p = 0.079). In luminal-like ILC (n = 85) at diagnosis, we found that OS after relapse was poorer in patients experiencing a phenotype switch to TNBC but improved in patients with HER2 gain (p = 0.0028). Poorer survival was reported in patients with a PgR and/or ER expression loss of ≥25%. There was HER2-low enrichment in M1 (from 37% to 58%): this change was not associated with OS (p > 0.05).
Our results suggest that phenotype switch after metastatic progression may be associated with patients' outcomes. Tumour biopsy in recurrent ILC could drive treatment decision-making, with prognostic implications.
浸润性小叶癌(ILC)具有独特的临床生物学特征。已经描述了原发性肿瘤(PT)和转移灶(M)之间浸润性导管癌的表型差异,但关于 ILC 的数据有限。
我们回顾性分析了 2013 年至 2020 年期间我院复发 ILC 患者的资料。我们评估了 PT 和 M 之间雌激素受体(ER)、孕激素受体(PgR)和 HER2 的不一致性,以了解其预后和治疗意义。
所有患者中有 13%(n=91)患有 ILC。我们观察到 15%、44%和 5%的 ER、PgR 和 HER2 状态在 PT 和 M 之间存在不一致。ER/PgR 不一致与受体丢失有关,而 HER2 主要由于获得而导致不一致。PT 表现为腔型表型(93%);6%和 1%为三阴性(TNBC)和 HER2 阳性。在 M 中,TNBC(16%)和 HER2 阳性(5%)的比例增加。无复发生存和总生存(OS)根据临床表型而不同,HER2+和 TNBC 的预后较差(p<0.001);转移进展后的 OS 不因表型而异(p=0.079)。在诊断时为腔型 ILC(n=85)中,我们发现复发后发生表型向 TNBC 转变的患者 OS 较差,但 HER2 获得的患者 OS 改善(p=0.0028)。PgR 和/或 ER 表达损失≥25%的患者生存率较差。M1 中存在 HER2 低表达富集(从 37%到 58%):这种变化与 OS 无关(p>0.05)。
我们的结果表明,转移进展后的表型转变可能与患者的预后相关。在复发的 ILC 中进行肿瘤活检可以指导治疗决策,并具有预后意义。