In the present study, we examined the effect of CT on the prognosis of MBC patients and explored the role of HR in CT under different risk of recurrence. After propensity score matching and using the variables as covariates considered importantly by some scholars, our results showed that only HR-positive patients with high risk could benefit from CT. Of note, CT might improve the short-term clinical outcomes for patients with intermediate-risk regardless of HR status.
Although the previous study reported MBC had a good survival, they had a small sample and short follow-up period. [26–29] A study reported median survival for metastatic MBC patients was less than 1 year. MBC patients with stage IV have different management and survival outcomes relative to patients with stage I-III. [19, 20] As mentioned above, we excluded MBC patients with distant metastasis.
The proportion of MBC receiving CT ranged from 33 to 86%. [13, 19, 31] On the one hand, patients receiving CT with a wide range may indicate that the effect of CT was not yet certain in MBC patients, although several small, single-institution and the single-arm study showed that CT could improve the prognosis of MBC. [32–34] On the other hand, patients receiving CT with a high rate may be due to their tendency to more common triple-negative phenotype and larger tumor size.  There was also another reason that the management strategy of MBC is similar to traditional breast cancer in the NCCN guideline. However, most studies had illustrated that CT might not affect the outcome of MBC. [2, 14, 17, 18] In our study, 62.5% of patients underwent CT but they cannot benefit from it, which was consistent with the previous study. [36, 37]. However, in the subtype analysis, only HR-positive patients with high risk could benefit from CT. That has not been appreciated so far. The reason for this effect could be the fact that our research population excluded patients with distant metastasis and follow-up was longer than published studies. Besides this, different risks of recurrence may be also worth considering.
HR-positivity has been considered as a biomarker as a better outcome for traditional breast cancer. However, previously published literature illustrated HR status was not associated with the prognosis of MBC. As reporting by Schroeder et al., for early and locally advanced MBC patients, HER2 but not HR status was associated with superior survival. In addition, they also found that survival was parallel between HER2-positive MBC and HER2-positive IDC. However, most researchers concluded that survival of MBC patients was the worse carcinoma in traditional breast cancer. [14, 18, 38] In many relatively consistent observation studies showed that MBC tended negative biomarkers. [ER, PR, HER2] [14, 39–41] Previous studies reported only 0–17% of cases expressed HR-positivity. [7, 8, 42] The expression of HR in MBC was uncommon. In the present study, 23.0% of patients were HR-positive cases. HR status was not a significant prognosticator in multivariate analysis, which was consistent with the result of Wright et al. reported. 
However, Wright et al. only conducted the Kaplan–Meier model and log-rank test without further analysis. In our study, subtype analysis was performed to explore the response of HR status to CT according to risk stratification before and after PSM. We found that patients with low risk cannot benefit from CT regardless of HR status. The reason for this phenomenon could be a smaller tumor size with a low risk of hematogenous metastasis. In addition, patients with intermediate-risk might benefit from CT regardless of HR status. However, patients with high risk benefited from CT only when they expressed HR-positivity. Such an occurrence probably accounts for HR-negative MBC patients with a worse prognosis than triple-negative breast cancer (TNBC).[14, 18, 37]
The European Society for Medical Oncology has adopted the statement that MBC patients are recommended to undergo CT from the 2013 St. Gallen consensus statement. The possible reason for this could be the fact that the HR status is commonly negative.[43, 44] A clinical overview study from Abouharb et al.  showed that the role of targeted therapies was a major investigation. Due to different molecular phenotypes, MBC can particularly benefit from these management strategies, as evidenced by Adams’ case report.  For this aggressive tumor, molecular analysis is important.
51.8% of patients were treated with mastectomy and 42.3% were treated with lumpectomy. Notably, mastectomy is performed more often for patients with MBC, likely due to the presentation with a larger tumor and triple-negative phenotype. However, in multivariate analysis, patients who underwent lumpectomy had better survival than patients who underwent a mastectomy. These data convinced us that breast-conserving therapy is an effective treatment strategy combined with other historical data for MBC patients.
There were several limitations to our study. Firstly, it was characterized by the observational nature and the possibility of selection bias because of its retrospective study. Secondly, the SEER database lacks baseline characteristics of MBC patients, including performance status, comorbidities, and socio-economic environment parameters. Thirdly, detailed chemotherapy regimens and radiotherapy information could not be available from the SEER database, so that further case-control study could not be performed. However, our results will help researchers to understand the role of molecular subtypes in the prognosis of MBC.
Our study has several key strengths. The involvement of CT in the prognosis of MBC is unclear. From our results, when stratified by recurrence risk, the prognosis was improved in MBC patients receiving CT. In addition, although studies had reported that HR status was not related to prognosis, HR status can redefine the role of chemotherapy in the prognosis of MBC.