Metaplastic breast cancer is a kind of heterogenous breast cancer, which is relatively rare in clinical practice. Despite several studies have found risk factors related to the clinical outcomes of MBC patients[9-11], there is no recognized prognostic factors to predict the prognosis of MBC. Paul Wright et al.[12] found that for patients with positive or negative hormone receptors, there was no significant difference in the 5-year survival rate of MBC, which indicated that the status of hormone receptors could not be considered as a prognostic factor of MBC. Additionally, previous study demonstrated that the subtype of MBC could be an independent predictor of its prognosis[3]. Several studies revealed that the prognosis of MBC patients with larger tumor and lymph node metastasis are generally poor[9, 13]. In recent years, some studies have also focused on the relationship between gene signatures and prognosis of MBC patients, such as the high expression of RPL39[11] and the mutation of the colony stimulating factor 1 receptor (CSF1R)[14], all of which can indicate poor prognosis.
However, single prognostic factors play a limited role in predicting individual survival probability. Nomograms are graphical display of mathematical models for predicting cancer risk, prevention and therapeutic outcomes, which becomes increasingly popular clinical decision aids thanks to their ability to deal with complex problems in a systematic and unbiased manner[15-17]. It has been revealed that nomograms exhibited more excellent prediction precision and prognostic value in diverse malignancies than the existing tumor system[18, 19]To construct a prognostic nomogram, we conducted univariate and multivariate analyses to find clinical characteristics that correlated with the OS and CSS of MBC patients on the basis of a large data set from the SEER database. We demonstrated that several clinicopathological characteristics were independent prognostic factors for OS, including age, grade, TNM stage, T stage, N stage, surg_prim_site, chemotherapy and radiotherapy. Furthermore, age, TNM stage, T stage, N stage, chemotherapy and radiotherapy were identified as independent prognostic factors for OS via multivariate analysis. In addition, grade, TNM stage, T stage, N stage, surg_prim_site and radiotherapy were found to be associated with CSS via univariate analysis, and further multivariate analysis confirmed that TNM stage, T stage, N stage and radiotherapy were independent prognostic factors for CSS of MBC patients. The nomograms established in this study showed favorable discrimination and calibration for 3-year and 5-year OS and CSS of MBC patients and offered a more accurate and personalized clinical tool for prognosis evaluation of MBC patients.
Prognostic studies have given conflicting results regarding factors associated with prognosis and survival [20-30]. In the present study, we critically evaluated the prognostic value of various factors based on a large cases of MBC recorded on the SEER. The clinical significance of age, TNM stage, T stage, N stage, chemotherapy, radiotherapy in MBC patients were highlighted in nomogram models. The result demonstrated that half of patients were older then 60 years, who suffered worst survival and poor OS. Of note, age showed no significant influence on CSS. Patients with older age generally accompanied a higher-risk histological phenotype[31], which has been considered as an independent risk factor and may eventually result in lower survival [31]. In these patients, surgical resection of the primary site is the mainstay of therapy with mastectomy more than lumpectomy, which was consistent with previous study[35]In addition, we found that chemotherapy is an independent prognostic factor for OS in MBC patients. Although it is correlated with CSS in univariate analysis, it is not an independent prognostic factor for CSS. It may result from the worse response to chemotherapy regimens in MBC[21, 25, 27, 36, 37]. Previous studies have concluded that radiotherapy was able to improve the survival of patients with MBC [8, 28, 38], and our data also demonstrated that radiation was independently prognostic factors associated with survival probability of patients with MBC. Moreover, radiotherapy was revealed to be able to reduce the risk of local recurrence[39]. T stage represents the tumor size and extrathyroidal extension, and our results demonstrated that T4 has an impact on OS and CSS in MBC patients, which was in line with previous population-based study of MBC [8]. LNM has been identified as a key prognostic indicator for a variety of malignancies, and the number of LNM has been included into the N-staging. Previous studies reported that lymph node status was significantly correlated with survival endpoints in patients with MBC [8]
There were several potential shortcomings in this study. First, retrospective data retrieved from the same database was used in the generation and validation of the nomogram models, which may lead to the risk of potential selection bias. Therefore, it would be more reliable to validate the nomograms in another dataset. Second, in this study, we only included two endpoints: 3- and 5-year survival. However, the assessment of recurrence risk is considered as a more meaningful endpoint than OS or CSS because of the rare specific mortality of MBC, which was not performed in this study owing to the lack of data with respect to recurrence in SEER database. Moreover, several other crucial prognostic factors, such as RET mutation status and calcitonin doubling times, were also unavailable in the SEER database