In the manuscript, we discovered that 4.13% of TNBC patients had DM at the time of diagnosis. Among DM patients, 3.07% had multiple metastases. The most metastatic sites were bone (24.46%, 251/1026) followed by lung (23.78%, 244/1026). Multivariate cox analysis indicated that age, high tumor grade, T, N and marital status were significant risk elements for DM. It is consistent with previous studies of other tumors [18–20]. In addition, T stage, insurance status, marital status, surgery treatment, chemotherapy, location and number of metastases were confirmed to be associated with the diagnosis of DM patients. Moreover, only TNBC was included in this study, which is more convincing to think that this data is the only representative of TNBC. Last but not least, with the rapid improvement in the understanding and diagnosis of the disease, earlier TNBC or smaller breast lumps will be detected in clinical practice.
There have also been previous studies on distant metastasis in BC patients. A retrospective study collected and analyzed information from 2033 BC patients from 2012 to 2014 and showed that high tumor grade, T, and N were significant risk factors for DM . Another study identified 1173 BC liver metastases from the SEER database. Classification, marital status, surgery, radiotherapy, chemotherapy, tumor size and tumor subtypes were identified as risk factors for liver metastases from BC . These conclusions are similar to our results. But only a few studies have focused on the triple negative subtype and combined metastatic pattern based on a larger sample size. In our study, 36.94% (379/1,026) of metastatic patients had multiple metastases. In addition, compared with patients with a single metastasis, patients with multiple metastases had a poorer survival advantage, and the more metastases there were, the worse the prognosis was (Table 4, 5). Furthermore, diverse combination of metastatic sites represented different prognosis.
Our results indicated that patients with DM have a significantly poor prognosis. Besides, the greater the number of metastases, the worse the prognosis. Hence, we further to identify the risk factors of DM and metastasis in patients with prognostic factors is very essential. In primary bladder cancer, high pathological grade, N and T were positively correlated with bone metastasis . Another meta-analysis showed that poor tumor differentiation was related to the risk of metastasis in cutaneous squamous cell carcinoma . In DM patients, the results of multi-COX analysis indicated that tumor grade, age at first diagnosis, T, N, marital status and surgical treatment were the significant influence affecting the OS. This is in line with what many previous studies have confirmed. In a BC study based on Asian female patients, age, grade, TNM stage, and chemotherapy have been shown to be associated with BC long-term survival . Another SEER database study found that race, age, grade, molecular subtype, surgery, brain and liver metastases were independently associated with BC specific survival .
However, there remain several limitations in our study that should not be ignored. First, we failed to get more information from SEER database, including lymphatic or vascular invasion, multifocality, the sequence and specific arrangement of multiple metastases and even molecular biomarkers. Secondly, the database lacked several important clinical information, including LDH, hemoglobin, neutrophil count, platelet count, etc. If we include these, we can improve the comprehensiveness of analysis and conclusion. Furthermore, limitations include a lack of information on rare subtypes of TNBC that may alter treatment, such as metaplasia, adenoid cystic, and acrosine subtypes. Last but not least, the main population for this study is Americans, and whether the results applied to other populations was questionable.