Background: The anti-tumor response of the immune system is pivotal for treating triple-negative breast cancer (TNBC), particularly as targeted therapies are limited. However, the impact of immune-modulating factors such as the application of granulocyte-stimulating factors (G-CSFs) or infections, including febrile neutropenia, prophylactic or therapeutical application of oral antibiotics (OABs), and the need for intravenous antibiotics (IABs), on survival outcomes remains unclear. Methods: 1583 patients with early-stage TNBC enrolled in the SUCCESS A or C study underwent primary surgery, adjuvant chemotherapy, and radiotherapy if indicated. All patients had Eastern Cooperative Oncology Group (ECOG) status ≤ 2. The effects of G-CSF, OAB, and IAB application on overall survival (OS), invasive disease-free survival (iDFS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were assessed. Results: Only IAB treatment was significantly associated with decreased survival in univariable analyses (OS:p= 0.003; iDFS:p= 0.036; BCSS:p= 0.011; DDFS:p= 0.044), while G-CSF and OAB administration were not. Adjusted multivariable Cox regressions including febrile neutropenia and dose reduction/shift, ECOG, age of patients, and other clinicopathological parameters confirmed a significant negative effect of IABs on OS (p= 0.020), BCSS (p= 0.018), and DDFS (p= 0.044). Conclusions: In summary, IABs during adjuvant chemotherapy seems to be a risk factor for inferior OS, BCSS, and DDFS in TNBC patients, possibly by affecting microbiome-related immune response modulation. Hence, preventive measures to avoid the need for IABs should be considered in these patients.
背景：免疫系统的抗肿瘤反应对治疗三阴性乳腺癌（TNBC）至关重要，尤其是在靶向治疗手段有限的情况下。然而，免疫调节因素（如粒细胞集落刺激因子（G-CSF）的应用或感染事件，包括发热性中性粒细胞减少症、预防性或治疗性口服抗生素（OAB）的使用，以及静脉抗生素（IAB）的应用需求）对生存结局的影响尚不明确。方法：本研究纳入SUCCESS A或C试验中1583例早期TNBC患者，所有患者均接受根治性手术、辅助化疗及必要的放疗，且美国东部肿瘤协作组（ECOG）体能状态评分≤2。评估G-CSF、OAB及IAB应用对总生存期（OS）、无浸润性疾病生存期（iDFS）、乳腺癌特异性生存期（BCSS）和无远处转移生存期（DDFS）的影响。结果：单变量分析显示，仅IAB治疗与生存率下降显著相关（OS：p=0.003；iDFS：p=0.036；BCSS：p=0.011；DDFS：p=0.044），而G-CSF和OAB的使用则无显著关联。经校正发热性中性粒细胞减少症、剂量调整/方案转换、ECOG评分、患者年龄及其他临床病理参数的多变量Cox回归分析证实，IAB对OS（p=0.020）、BCSS（p=0.018）和DDFS（p=0.044）具有显著负面影响。结论：综上所述，辅助化疗期间使用IAB可能是TNBC患者OS、BCSS和DDFS降低的风险因素，其机制可能与影响微生物组相关的免疫调节有关。因此，应考虑采取预防措施以避免此类患者对IAB的需求。
肿瘤(癌症)患者之家