The total number of young breast cancers is relatively small, but the incidence of distant metastasis is increasing. The incidence of MBC among young women increased from 1.53 per 100,000 to 2.90 per 100,000 from 1976 to 2009, with the trend showing no slowing down, indicating increasing epidemiological and clinical significance. However, there are few studies on young women with MBC. Our study divided MBC patients into three age groups in a large population-based SEER data to evaluate the effect of age on metastasis patterns and the effect of age, metastasis sites, and molecular subtype on prognosis.
Our study showed that young MBC patients had larger tumors, higher rates of lymph node involvement, and more aggressive molecular types, consistent with previous studies. The largest study to date involving 200,000 breast cancer patients was conducted by Gnerlichetal with 15,000 breast cancer patients aged < 40 years at diagnosis, found that younger women were more likely to be diagnosed with larger tumors, lymph node involvement, poorly differentiated tumors, and ER-tumors. In addition, a California Cancer Registry study  including 5600 women aged < 40 years at diagnosis reported a statistically significant HER2-higher expression in the younger women. The results of these studies demonstrate the aggressiveness of breast cancer in young patients. In addition, the screening is poor in young women due to the low incidence of breast cancer, which leads to more severe disease at the time of diagnosis.
The metastasis patterns in different age groups remains controversial. A study of 14,403 patients based on the ESME database found that MBC patients aged < 40 years were more likely to have visceral metastasis than bone metastasis. Chen et al found that MBC patients aged < 50 years were more likely to have distant lymph node metastasis, multiple sites metastasis, and less likely to have lung metastasis. A study of 6,640 patients showed that MBC patients aged < 40 years were more likely to have brain and liver metastasis than patients aged ≥ 40 years. Our study found that MBC patients aged ≤ 40 years had a higher risk of liver metastasis, while the risk of lung metastasis was lower. This may be due to more HER2 + and triple-negetive subtypes in young patients. Previous studies have shown that HER2 + subtype is associated with liver metastasis.[19, 20] HER2 + and triple-negetive subtypes were more likely to have visceral metastasis than bone metastasis. However, the underlying molecular mechanisms need further research.
Multivariate COX regression showed that the OS and BCSS of the younger group were better than those of the middle-aged group and the older group, and youth was an independent protective factor of prognosis. This is contrary to previous studies reported that young age at diagnosis is associated with poor prognosis in breast cancer. There are many reasons for this. First, our study confirmed that younger patients were more likely to receive treatment (surgery, chemotherapy, radiotherapy), consistent with previous studies . Besides conventional systemic treatment, many studies have demonstrated the benefits of local treatment for MBC [22、23]. Second, there were more Her2 + subtypes in young patients. Studies have found that the improvement of OS in MBC patients is mainly driven by the HER2 + subgroup . In fact, new HER2-targeted therapies were released in 2013 (namely pertuzumab and T-DM1), which were associated with major OS benefits in clinical trials [25–27]. In a real-world study of patients with HER2 + MBC, younger patients were more likely to receive PH + taxane than older patients, and older patients were more likely to receive regimens with H without P or hormone therapy. It turned out younger patients have better BCSS than older patients. This also suggests that there may be undertreatment in elderly patients to some extent.
Kaplan-Meier analysis showed interesting results. In the younger group, patients with liver only metastasis, not bone only metastasis, had the best prognosis. This may be due to the fact that 59.2% of patients with liver metastasis were HER2 + subtypes in the younger group of our study, and younger patients received more chemotherapy and anti-HER2 therapy than older patients, bringing survival benefits. SwatiSakhuja et al.  found that HR-/HER2 + and HR+/HER2 + subtypes had the best survival in patients with liver metastasis. Ji et al.  also reached the same conclusion. Similarly, HER2 + subtype in the younger group also showed a survival advantage in our study. This suggests that even in metastatic HER2 + breast cancer, anti-HER2 therapy also result in considerable and long-lasting improvements in survival.
There are some limitations to this study. This study was retrospective and not as convincing as prospective studies. The SEER database does not provide information on targeted therapy or endocrine therapy, which may affect survival outcomes. In addition, the SEER database only provided HER2 information after 2010, resulting in insufficient follow-up of some patients. Despite these limitations, this study elucidates the metastasis patterns and prognostic characteristics based on metastasis sites and molecular subtype in young MBC patients. These findings may provide a basis for precision treatment of young MBC patients.