In this era of individualized therapy, accurate prediction of prognosis in patients with BCLM is very important for clinicians to make treatment options and communicate effectively with patients and family members. In the present study, we described sociodemographic and clinicopathological parameters in patients with lung metastases. In addition, we constructed variable factors related to the prognosis of lung metastases and verified nomograms to precisely predict the prognosis of BCLM patients.
Lung metastasis is one of the common sites of metastatic breast cancer (MBC). Patients with lung metastases are all classified in stage IV based on AJCC TNM staging system, which could not supply individualized prognostic information for clinicians and patients. Therefore, there is an increasing need for developing effective models to predict the prognosis of BCLM patients. Previously, Xiao et al. proposed that the prognosis of patients with BCLM may be related to age, subtype, pathological grade, number of metastatic sites, and marital status. However, this study neither included the influence of treatment methods nor proposed a prognostic nomogram related to survival. (16) Here, treatment methods, including chemotherapy, surgery, and neoadjuvant therapy, were screened in our study, and a survival model was also proposed based on the relevant factors.
Nomogram was constructed by performing univariate and multivariate COX regression analyses on the prognostic factors (age, race, marital status, years of diagnosis, laterality, primary site, tumor size, histopathology, grade, tumor stage, nodal stage, metastatic stage, clinical stage, and Immunohistochemical type) of the breast cancer database (ICD-0-3) in SEER. NRI and IDI suggest that our nomograms better identify unfavorable OS compared with traditional TNM staging. The calibration curve was constructed and showed great agreement in predicted survival probability and actual of BCLM by the good alignment of 1-, 2-, and 3-year survival rates with ideal (K = 1).
The nomogram can completely reflect the individual differences of patients because it quantifies the risk non-invasively and quantitatively on a macro scale, which makes the nomogram have better performance in predicting OS than the traditional TNM staging. The accuracy of models is in direct proportion to their complexity, and we try to make a balance between comprehensiveness and clinical usefulness. Therefore, we selected 13 prognostic factors with clinical importance and a small time-varying effect to construct a nomogram. In the present study, we declared several of our findings. Firstly, our nomograms demonstrated that young patients (< 35) have a better prognosis, which is different from previous studies. (17) Secondly, the OS of patients with lung metastasis of TNBC was worse than that of other types of BCLM. (18) Thirdly, in terms of pathological classification, our results showed that the prognosis of patients with invasive ductal carcinoma (IDC) is better than that of invasive lobular carcinoma (ILC). Fourthly, in terms of immunohistochemistry, patients with ER and PR had a better prognosis, presumably due to the opportunity for endocrine therapy. Finally, patients underwent neoadjuvant chemotherapy had a prolonged OS.
Chemotherapy and neoadjuvant therapy significantly improve the prognosis of patients with BCLM. Although some studies do not support neoadjuvant therapy has a positive effect on the long-term survival of MBC patients, our nomogram suggests that neoadjuvant therapy is beneficial for the survival of patients with BCLM, even if they develop lung metastases after neoadjuvant therapy. It may be because neoadjuvant therapy can help clinicians transition from ‘clinic-based choice’ to ‘molecular-tailored chemotherapy’ to prolong the survival of patients.
Social, mental, and emotional stress are thought to be associated with cancer. As a systemic disease, breast cancer might be the result of a complex interaction of physiological and psychosocial factors. In our study, a sociodemographic factor—marital status was included in our research. Accumulating evidence shows that marital status is an independent prognostic factor affecting the survival of breast cancer patients. (19) Here, we found that the prognosis was worse when a patient was in a relationship of "divorced" or "widowed" than “married” or “unmarried”. It is speculated that in addition to the physical burden of the tumor, these patients have to face the emotional stress and grief of losing their spouse and the material support from their partner. Some studies suggested that the frequency of “widows” receiving chemotherapy and their tolerance of chemotherapy are lower than those of “married” patients, which may be related to the inhibited response of peripheral blood lymphocyte stimulation of widowed patients, which leads to worse OS of widowed patients than those of other marital statuses. (20, 21)
Our study, based on SEER database, improves the accuracy of independent risk factors that predict prognosis in patients with BCLM. However, we used data from BCLM in the SEER database from 2010 to 2015, which brought limitations to this study. In our opinion, the number and maximum diameter of lung metastases, KI67 expression level, ER expression intensity, lifestyle, economic conditions, and other factors might be associated with the prognosis. Unfortunately, this information could not be obtained from the 2010–2015 SEER database. Therefore, other relevant factors are needed to further correct and supplement the nomogram in future studies