吸烟对复发性乳腺癌生物学变化的影响。

The effect of smoking on biological change of recurrent breast cancer.

机构信息

Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Department of Scientific and Linguistic Fundamentals of Nursing, Osaka City University Graduate School of Nursing, 1-5-17 Asahi-machi, Abeno-ku, Osaka, 545-0051, Japan.

出版信息

J Transl Med. 2020 Apr 5;18(1):153. doi: 10.1186/s12967-020-02307-x.

DOI:10.1186/s12967-020-02307-x

PMID:32248830

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7132886/

Abstract

BACKGROUND

The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence.

METHODS

This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined.

RESULTS

When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p = 0.024).

CONCLUSIONS

Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.

摘要

背景

乳腺癌患者的治疗选择在很大程度上依赖于癌症亚型。然而，这一过程因肿瘤生物学在复发时的变化而变得复杂。吸烟已被确定为乳腺癌的一个风险因素。通过血液循环输送的烟草成分对乳腺组织的直接影响以及随后的 DNA 损伤，被认为可以解释吸烟与乳腺癌发生之间的关联。组织培养和动物研究都支持这一假设，这些研究表明，相关的 DNA 损伤进一步改变乳腺癌细胞，表现为增殖能力增强和恶性转化。在这项研究中，我们旨在探讨复发时每个受体（雌激素受体[ER]、孕激素受体[PgR]和人表皮生长因子受体 2[HER2]）的变化与吸烟以及复发后的预后之间的关系。

方法

这项回顾性研究纳入了 989 名接受手术治疗后复发的原发性乳腺癌患者和 50 名 2007 年 12 月至 2018 年 3 月接受再生活检或手术的患者。使用免疫组织化学评估原发性和复发性病变中 ER、PgR 和 HER2 的表达，并检查这些表达模式与吸烟史（包年）的相关性。

结果

当评估复发性肿瘤中的 ER 时，分别有 3 例（6.0%）和 1 例（2.0%）患者出现阴性和阳性转换。当评估 PgR 时，15 例患者（30.0%）出现阴性转化。当评估 HER2 时，有 6 例患者（12.0%）出现阳性转换。因此，我们观察到 5 例复发性肿瘤患者的固有亚型发生了变化（10.0%）。尽管大多数临床因素与吸烟无关，但复发时 HER2 的阳性转换在吸烟者中比在非吸烟者中更为频繁（p=0.024）。