Introduction

Breast cancer (BC) is frequent with a poor prognosis in case of metastasis. The role of the environment has been poorly evaluated in its progression. We searched to assess whether a mixture of pollutants could be responsible of BC aggressiveness.

Methods

Patients undergoing surgery for their BC were prospectively included in the METAPOP cohort. Forty-two POPs were extracted, among them 17 dioxins (PCDD/F), 16 polychlorobiphenyls (PCB), 8 polybromodiphenylethers (PBDE) and 2,2′,4,4′,5,5′-hexabromobiphenyl (PBB153) were measured in the adipose tissue surrounding the tumor. BC aggressiveness was defined using tumor size and metastasis (distant or lymph nodes). Two complementary models were used to evaluate the impact of the mixture of pollutants: the BKMR (Bayesian Kernel machine regression) and WQS (weighted quantile sum regression) models. The WQS estimates the weight (positive or negative) of a certain chemical based on its quantile and the BKMR model applies a kernel-based approach to estimate posterior inclusion probabilities. The sub-group of patients with a body mass index (BMI) > 22 kg/ m² was also analyzed.

Results

Ninety-one patients were included. Of these, 38 patients presented a metastasis, and the mean tumor size was 25.4 mm. The mean BMI was 24.5 kg/m² (+/- 4.1). No statistical association was found in the general population. However, in patients with a BMI > 22 kg/ m², our mixture was positively associated with tumor size (OR: 9.73 95 %CI: 1.30–18.15) and metastasis (OR = 3.98 95 %CI = 1.09–17.53) using the WQS model. Moreover, using the BKMR model on chemical families, dioxin like chemicals and PCDD were associated with a higher risk of metastasis.

Discussion

These novel findings identified a mixture associated with breast cancer aggressiveness in patients with a BMI > 22 kg/ m².

中文翻译：

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持久性有机污染物混合物对乳腺癌侵袭性的影响

介绍

乳腺癌 (BC) 很常见，如果发生转移，预后很差。环境的作用在其发展过程中没有得到很好的评估。我们进行了搜索以评估污染物的混合物是否会导致 BC 侵略性。

方法

接受 BC 手术的患者被前瞻性地纳入 METAPOP 队列。提取42种持久性有机污染物，其中测得17种二恶英（PCDD/F）、16种多氯联苯（PCB）、8种多溴二苯醚（PBDE）和2,2',4,4',5,5'-六溴联苯（PBB153）在肿瘤周围的脂肪组织中。BC 侵袭性是使用肿瘤大小和转移（远处或淋巴结）来定义的。两个互补模型用于评估污染物混合物的影响：BKMR（贝叶斯核机器回归）和 WQS（加权分位数和回归）模型。WQS 根据其分位数估计某种化学物质的权重（正或负），而 BKMR 模型应用基于核的方法来估计后验包含概率。体重指数 (BMI) > 22 kg/m的患者亚组²也进行了分析。

结果

包括 91 名患者。其中，38 名患者出现转移，平均肿瘤大小为 25.4 毫米。平均 BMI 为 24.5 kg/m ² (+/- 4.1)。在一般人群中未发现统计关联。然而，在 BMI > 22 kg/m ²的患者中，我们的混合物与肿瘤大小 (OR: 9.73 95 %CI: 1.30–18.15) 和转移 (OR = 3.98 95 %CI = 1.09–17.53) 呈正相关WQS模型。此外，使用化学家族的 BKMR 模型，二恶英类化学物质和 PCDD 与更高的转移风险相关。

讨论

^{这些新发现确定了与 BMI > 22 kg/m 2}患者的乳腺癌侵袭性相关的混合物。