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体重指数与乳腺癌免疫组化亚型之间的关联。

The association between body mass index and immunohistochemical subtypes in breast cancer.

作者信息

Sahin Suleyman, Erdem Gokmen U, Karatas Fatih, Aytekin Aydin, Sever Ali R, Ozisik Yavuz, Altundag Kadri

机构信息

Department of Medical Oncology, Diskapi Training and Research Hospital, Ankara, Turkey.

Department of Medical Oncology, Numune Training and Research Hospital, Ankara, Turkey.

出版信息

Breast. 2017 Apr;32:227-236. doi: 10.1016/j.breast.2016.09.019. Epub 2016 Oct 15.

Abstract

BACKGROUND

Body mass index (BMI) is defined as a poor prognostic factor in patients with breast cancer (BC). However, there are controversial results regarding the various effects of BMI on BC, hence the exact pathophysiology of the relation between obesity and BC is still under debate, and remains unclear. This paper aims to investigate the association between BMI at presentation and BC subtypes defined according to the immunohistochemical classification in both premenopausal and postmenopausal patients with BC.

PATIENTS AND METHODS

This study is a retrospective and explorative analysis of the 3767 female BC patients from a single center. All patients' BMI at the time of initial diagnosis and tumor demographics were recorded. BMI was stratified into 3 groups as normal-weighted (BMI <25 kg/m), over-weighted (BMI = 25-29.9 kg/m), and obese (BMI ≥30 kg/m). Immunohistochemical classification of the tumors was categorized into 4 groups as follows; luminal-like, HER2/luminal-like, HER2-like, and triple-negative according to the ER/PR and HER2 status. Distribution of Immunohistochemical subtypes, tumor characteristics, and overall survival (OS) analysis were evaluated according to the BMI groups in both premenopausal and postmenopausal patients.

RESULTS

Median BMI of premenopausal and postmenopausal patients was 25.5 (kg/m) and 28.8 (kg/m), respectively (P < 0.001). In parallel with the increasing age, patients were more obese at diagnosis in both premenopausal (P < 0.001) and postmenopausal period (P < 0.001). Triple-negative subtype was significantly more frequent in premenopausal patients with BMI ≥30 kg/m compared to BMI <30 kg/m (P = 0.007). Additionally, premenopausal patients with BMI ≥30 kg/m had less common luminal-like subtype (P = 0.033) and more frequently presented with higher tumor stage (P = 0.012) and tumor grade (P = 0.004) compared to patients with BMI <25 kg/m. On the other hand, premenopausal patients with BMI <25 kg/m had significantly more ER-positive tumors (P < 0.001) and lower stages of disease (P = 0.01) compared to their counterparts with BMI ≥25 kg/m. Premenopausal obese patients with triple-negative (P = 0.001) and luminal-like subtype (P = 0.002) had significantly shorter OS duration compared to overweight counterparts. HER2/luminal-like subtype was found to be significantly greater in postmenopausal overweight patients (P = 0.005). However, BMI had no any other significant effect on survival and immunohistochemical subtypes in postmenopausal patients. Multivariate analysis revealed that triple-negative subtype, grade III tumor, BMI ≥30 kg/m, T3-4 (P < 0.001), nodal involvement, metastatic disease, and lymphovascular involvement were significantly associated with poorer OS.

CONCLUSION

Our data indicated that BMI was an independent factor in patients with BC, with an association indicating a decreased incidence for luminal-like subtype and increased incidence for triple-negative subtype among premenopausal patients. However, this significance was not found in postmenopausal patients. Accordingly, a plausible etiological heterogeneity in BC might play a role among immunohistochemical subtypes in every life stage of women.

摘要

背景

体重指数(BMI)被定义为乳腺癌(BC)患者的不良预后因素。然而,关于BMI对BC的各种影响存在争议性结果,因此肥胖与BC之间关系的确切病理生理学仍在争论中,尚不清楚。本文旨在研究绝经前和绝经后BC患者就诊时的BMI与根据免疫组织化学分类定义的BC亚型之间的关联。

患者与方法

本研究是对来自单一中心的3767例女性BC患者进行的回顾性探索性分析。记录了所有患者初次诊断时的BMI和肿瘤特征。BMI分为3组:正常体重(BMI<25kg/m²)、超重(BMI=25-29.9kg/m²)和肥胖(BMI≥30kg/m²)。根据ER/PR和HER2状态,将肿瘤的免疫组织化学分类分为4组:管腔样、HER2/管腔样、HER2样和三阴性。根据绝经前和绝经后患者的BMI组评估免疫组织化学亚型的分布、肿瘤特征和总生存期(OS)分析。

结果

绝经前和绝经后患者的中位BMI分别为25.5(kg/m²)和28.8(kg/m²)(P<0.001)。随着年龄的增长,绝经前(P<0.001)和绝经后(P<0.001)患者在诊断时更肥胖。与BMI<30kg/m²的绝经前患者相比,BMI≥30kg/m²的绝经前患者中三阴性亚型明显更常见(P=0.007)。此外,与BMI<25kg/m²的患者相比,BMI≥30kg/m²的绝经前患者管腔样亚型较少见(P=0.033),且肿瘤分期较高(P=0.012)和肿瘤分级较高(P=0.004)的情况更常见。另一方面,与BMI≥25kg/m²的患者相比,BMI<25kg/m²的绝经前患者ER阳性肿瘤明显更多(P<0.001),疾病分期更低(P=0.01)。与超重的绝经前肥胖患者相比,三阴性(P=0.001)和管腔样亚型(P=0.002)的绝经前肥胖患者的OS持续时间明显更短。在绝经后超重患者中发现HER2/管腔样亚型明显更多(P=0.005)。然而,BMI对绝经后患者的生存和免疫组织化学亚型没有任何其他显著影响。多因素分析显示,三阴性亚型、III级肿瘤、BMI≥30kg/m²、T3-4(P<0.001)、淋巴结受累情况、转移性疾病和淋巴管受累与较差的OS显著相关。

结论

我们的数据表明,BMI是BC患者的一个独立因素,在绝经前患者中,其与管腔样亚型发病率降低和三阴性亚型发病率增加相关。然而,在绝经后患者中未发现这种显著性。因此,BC中可能存在的病因异质性可能在女性每个生命阶段的免疫组织化学亚型中起作用。

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