Oniris, Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, Animal cancers, Models for Research in Comparative Oncology (AMaROC), Site de la Chantrerie, Route de Gachet, CS40706, 44307, Nantes, France.
CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.
Breast Cancer Res Treat. 2018 Jan;167(2):459-468. doi: 10.1007/s10549-017-4542-8. Epub 2017 Oct 23.
Relevant animal models of human breast cancer are currently needed, especially for the aggressive triple-negative breast cancer subtype. Recent studies and our results (Part 1) indicate that spontaneous canine invasive mammary carcinomas (CMCs) resemble human breast cancer by clinics and pathology as well as behavior and prognostic indicators. We hypothesized that the current molecular classifications of human breast cancer, used for therapeutic decision, could be relevant to dogs.
Three hundred and fifty female dogs with spontaneous CMC and a 2-year follow-up were retrospectively included. By immunohistochemistry, CMCs were classified according to Nielsen (Clin Cancer Res 10:5367-5374, 2004) and Blows (PlosOne doi: 10.1371/journal.pmed.1000279, 2010) into the subtypes of human breast cancer.
Four immunophenotypes were defined either according to Nielsen classification (luminal A 14.3%, luminal B 9.4%, triple-negative basal-like 58.6%, and triple-negative nonbasal-like 17.7% CMCs); or to Blows classification (luminal 1-: 11.4%, luminal 1+: 12.3%, Core basal phenotype: 58.6%, and five-negative phenotype: 17.7%). No HER2-overexpressing CMC as defined by a 3 + immunohistochemical score was observed in our cohort. By univariate and multivariate analyses, both immunophenotypical classifications applied to CMCs showed strong prognostic significance: luminal A or luminal 1+ CMCs showed a significantly longer disease-free interval (HR = 0.46), Overall (HR = 0.47), and Specific Survival (HR = 0.56) compared to triple-negative carcinomas, after adjustment for stage.
In our cohort, triple-negative CMCs largely predominated (76%), were much more prevalent than in human beings, and showed an aggressive natural behavior after mastectomy. Dogs are thus potent valuable spontaneous models to test new therapeutic strategies for this particular subtype of breast cancer.
目前需要人类乳腺癌的相关动物模型，特别是对于侵袭性三阴性乳腺癌亚型。最近的研究和我们的结果（第一部分）表明，自发性犬浸润性乳腺肿瘤（CMCs）在临床和病理学、行为和预后指标方面与人类乳腺癌相似。我们假设，目前用于治疗决策的人类乳腺癌分子分类可能与狗有关。
回顾性纳入 355 只患有自发性 CMC 并随访 2 年的雌性狗。通过免疫组织化学，根据尼尔森（Clin Cancer Res 10:5367-5374, 2004）和布洛斯（PlosOne doi: 10.1371/journal.pmed.1000279, 2010）将 CMC 分类为人类乳腺癌的亚型。
根据尼尔森分类（luminal A 14.3%、luminal B 9.4%、三阴性基底样 58.6%和三阴性非基底样 17.7% CMCs）或布洛斯分类（luminal 1-：11.4%、luminal 1+：12.3%、核心基底表型：58.6%和五阴性表型：17.7%），定义了四种免疫表型。在我们的队列中，没有观察到由 3+免疫组织化学评分定义的 HER2 过表达 CMC。通过单变量和多变量分析，应用于 CMCs 的两种免疫表型分类均显示出强烈的预后意义：与三阴性癌相比，luminal A 或 luminal 1+ CMCs 的无病间隔（HR=0.46）、总生存期（HR=0.47）和特异性生存期（HR=0.56）显著延长，调整分期后。
在我们的队列中，三阴性 CMCs 占很大比例（76%），比人类更为常见，并且在乳房切除术后表现出侵袭性自然行为。因此，狗是测试这种特殊乳腺癌亚型新治疗策略的有力自发模型。
