Department of Clinical Sciences & Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
PLoS One. 2020 Aug 10;15(8):e0236516. doi: 10.1371/journal.pone.0236516. eCollection 2020.
Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors.
乳腺癌是全球女性癌症相关死亡的最常见原因。鉴定可靠的预后指标和治疗靶点对于改善患者预后至关重要。伴侣动物的癌症通常与人类癌症非常相似，通过比较方法来鉴定预后标志物可以改善跨物种的临床护理。猫乳腺肿瘤（FMT）是人类三阴性乳腺癌（TNBC）的极侵袭性模型，切除后局部和远处复发率很高。尽管大多数 FMT 的临床行为具有侵袭性，但目前的预后指标不足以准确预测预后，与人类患者相似。鉴于乳腺肿瘤的显著异质性，最近人们关注鉴定普遍存在的肿瘤允许性基质特征，这些特征可以预测生物学行为，并提供治疗靶点以改善预后。与人类和犬科患者一样，胶原蛋白特征似乎在指导猫科患者乳腺肿瘤行为方面发挥着关键作用。我们发现，患有 FMT 的患者胶原更密集，纤维更长、更厚、更直，肿瘤-基质边界更不明显，其预后更差，与临床变量分级和手术切缘无关。最重要的是，包括胶原参数在内可以提高临床模型的预测能力。因此，我们的数据表明，物种间基质微环境的相似性可能使该模型能够预测预后，并在肿瘤基质中开发新的治疗靶点，从而使具有侵袭性乳腺肿瘤的兽医和人类患者受益。
