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. 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. 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). 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.

中文翻译：

---

吸烟对复发性乳腺癌生物学变化的影响。

乳腺癌患者的治疗选择主要取决于癌症亚型。然而，该过程由于复发时肿瘤生物学的改变而变得复杂。吸烟已被确定为乳腺癌的危险因素。已经提出了通过血液循环传递的烟草成分对乳腺组织的直接作用以及随后的DNA损伤，以解释吸烟与乳腺癌癌变之间的关系。组织培养和动物研究均支持这种假设，表明相关的DNA损伤进一步改变了乳腺癌细胞，如增生能力和恶性转化所表明。在这项研究中，我们旨在探讨雌激素受体（ER），孕激素受体（PgR），与人表皮生长因子受体2（HER2）的每个受体在复发时，以及吸烟与复发后的预后有关。这项回顾性研究包括989例原发性乳腺癌患者，这些患者在手术后复发，并从2007年12月至2018年3月进行了50例进行了再生活检或手术的患者。研究了这些表达方式与吸烟史（包装年）的相关性。在复发性肿瘤中评估ER时，分别在3名（6.0％）和1名患者（2.0％）中发现了阴性和阳性转化。当评估PgR时，在15例患者中发现了负转化（30.0％）。在评估HER2时，有6例患者（12.0％）被确认为阳性转化。因此，我们观察到5例复发性肿瘤患者的内在亚型发生了改变（10.0％）。尽管大多数临床因素与吸烟无关，但吸烟者中HER2阳性转化率显着高于非吸烟者（p = 0.024）。乳腺癌复发期间的生物学变化应给予认真的临床考虑，因为它们会影响复发后的治疗。我们的结果表明，吸烟可能会导致复发性乳腺肿瘤中HER2表达增加。乳腺癌复发期间的生物学变化应给予认真的临床考虑，因为它们会影响复发后的治疗。我们的结果表明，吸烟可能会导致复发性乳腺肿瘤中HER2表达增加。乳腺癌复发期间的生物学变化应给予认真的临床考虑，因为它们会影响复发后的治疗。我们的结果表明，吸烟可能会导致复发性乳腺肿瘤中HER2表达增加。