INSERM UMR-S 1124, 45 rue des Saints-Pères, 75006 Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Service de Chirurgie Cancérologique Gynécologique et du Sein, Paris, France; Université de Paris, 45 rue des Saints-Pères, 75006 Paris, France.
LABERCA, Oniris, INRA, Université Bretagne-Loire, 44307 Nantes, France.
Environ Int. 2019 Nov;132:105028. doi: 10.1016/j.envint.2019.105028. Epub 2019 Aug 2.
Breast cancer (BC) is a major public health concern with over 2 million new cases diagnosed and over 600,000 deaths in 2018 in women worldwide. When distant metastases are present at diagnosis, the 5-year survival rate is only 26%. Recent studies have suggested that persistent organic pollutants (POPs) that accumulate in adipose tissue (AT) can influence tumor phenotype and stimulate cellular processes important for metastasis such as invasion. We, therefore, tested the hypothesis that POP exposure is associated with BC metastasis.
We conducted an exploratory case-control study in which the concentrations of 49 POPs were measured in both AT and serum samples from BC patients, with or without lymph node metastasis, who underwent partial or total mastectomies, lymph node biopsies and sampling of the adipocytic tumor microenvironment. Adjusted, unconditional logistic models were used to study the associations between the POP concentrations and the risk of metastasis and other hallmarks of cancer aggressiveness.
2.3.7.8-TCDD concentrations in AT are positively associated with the risk of metastasis in 43 patients who have BMIs equal or higher than 25 kg/m2 (odds ratio: 4.48 (1.32-20.71)). Furthermore, the concentrations of 2.3.7.8-TCDD and two coplanar PCBs (77&169) in AT also were positively associated with the risk of lymph node metastasis and the tumor size.
Our study suggests that 2.3.7.8-TCDD and some PCBs contribute to the development of tumor metastasis and other hallmarks of cancer aggressiveness. While these results should be considered with caution, this is the first study to identify such potential risk factors. Larger longitudinal studies are necessary to confirm our results. Clinical Trial Protocol Record: 2013-A00663-42.
乳腺癌（BC）是一个重大的公共卫生关注点，全球范围内 2018 年新诊断出超过 200 万例病例，并有超过 60 万例死亡病例。当远处转移在诊断时出现时，5 年生存率仅为 26%。最近的研究表明，蓄积在脂肪组织（AT）中的持久性有机污染物（POPs）可以影响肿瘤表型并刺激对转移很重要的细胞过程，如侵袭。因此，我们检验了 POP 暴露与 BC 转移相关的假设。
我们进行了一项探索性病例对照研究，其中测量了 49 种 POPs 在乳腺癌患者的 AT 和血清样本中的浓度，这些患者接受了部分或全乳房切除术、淋巴结活检以及脂肪肿瘤微环境样本的采集，这些患者有或没有淋巴结转移。使用调整后的非条件逻辑模型研究了 POP 浓度与转移风险以及癌症侵袭性其他标志物之间的关联。
在 BMI 等于或高于 25kg/m2 的 43 名患者中，AT 中的 2.3.7.8-TCDD 浓度与转移风险呈正相关（比值比：4.48（1.32-20.71））。此外，AT 中的 2.3.7.8-TCDD 和两种共平面 PCB（77&169）的浓度也与淋巴结转移和肿瘤大小的风险呈正相关。
我们的研究表明，2.3.7.8-TCDD 和一些 PCB 有助于肿瘤转移和癌症侵袭性的其他标志物的发展。虽然这些结果应谨慎考虑，但这是首次确定此类潜在危险因素的研究。需要更大的纵向研究来证实我们的结果。临床试验方案记录：2013-A00663-42。
