Bones metastases are the most common distant metastatic site in breast cancer, severe complications, low quality of life and poor prognosis in patients, the rate of survival significantly decreased are often associated with the occurrence of bone metastases . Our study analyzed recently available data on the subtype in stage IV patients bone metastatic breast cancer patients from the SEER registries, in an attempt to analysis differences in the effects of the breast cancer subtype and other factors on the patient prognosis.
Bone metastasis is most abundant among the HR+ subtype, the distribution of our study stage IV patients tumour subtype is similar to other studies in the published literature [12, 19, 20]. Our studies have identified the subgroups of stage IV patients with HR+/HER2- breast cancer is the most prone to bone metastasis, secondly is HR+/HER2+ breast cancer. HR-/HER2- has a particular propensity to metastasize to the brain and lung, brain metastasis is more common than for the other subtype, and the bone metastasis is relatively less likely to occur, this is consistent with previous research . This may be due to different molecular subtype of breast cancer lead to different metastasis sites due to their special molecular biological characteristics.
The median OS for the entire cohort was 38 months of the patients, this is similar with Kuchuk’s study that from 294 electronic records of metastatic breast cancer patients were reviewed, they found the median OS from bone metastasis diagnosis is 40 months in bone metastasis patients . The median OS is 46 months for stage IV patients with only bone metastases, those with bone and other sites metastases is 24 months in our study is similar to the survival reported by previous authors in recent years . Study of 815 patients with denovo or recurrent metastatic breast cancer and identified that patients with visceral metastases as well as those with multiple metastatic sites had worse OS, findings consistent with our results . The five year survival rate is 33.9% which is similar with previous studies that shown 24–39% of patients alive in five year after diagnosis of bone metastases . It may be due to the fact that the subjects of this study are menopausal women, the age of the previous subjects is unlimited, the proportion of elderly patients is large and the prognosis is poor, and with the improving of treatment methods in recent years, the prognosis of the patients has been improved.
Our study shown the five-year survival rate of HR+/HER2+ stage IV patients is the highest, reached 5.6 times of HR-/HER2- patients. Stage IV Patients with HR+/HER2+ breast cancer had the longest median survival period. However, our study have shown that the incidence of bone metastasis in HR-/HER2- breast cancer was low, but stage IV patients with HR-/HER2- tumour had the worst prognosis. And OS in stage IV patients with HR-/HER2- breast cancer were significantly lower than those in stage IV patients with other molecular subtype, with the shortest median survival time. The large difference in prognosis observed across all tumour subtype confirms that breast cancer is a heterogeneous disease, even in the specific group of patients with bone metastases. The improvements in OS seen in HER2+ patients could be explained in part by the efficacy of HER2-targeted agents. In Dawood’s large-scale, randomized study , there were 2019 women with metastatic breast cancer that showed HER2+ patients who received trastuzumab had improved prognosis compared with HER2- patients . However, the HR-/HER2- is an invasion subtype, with the characteristics of rapid progress, strong aggressiveness, high degree of malignancy, easy occurrence of distant metastasis, rapid relapse [25-27]. Therefore, Our study includes tumour subtype as a prognostic factor and provides evidence of a clear association of age, race, marital status, insurance, tumour grade, histology, subtype, and visceral metastases in bone metastasis patients with OS. This was similar with previous study. The Denmark data were population-based health registries, included all women in diagnosed during 1999–2011 with regional or stage II/III breast cancer, showed predictors of recurrence, metastases, and mortality included age, hormone receptor status, and stage at diagnosis . Ahn’s study showed ER- negative and bone metastasis combined with visceral metastasis is a risk factor for OS . Iqbal J’s study showed US women diagnosed with invasive breast cancer, the survival varied by race and ethnicity, black women are more likely to die due to breast cancer within 7 years compared with non-Hispanic white or Asian women . Previous study observed that Hispanics and Non-Hispanic Blacks were more likely to have ER-positive and PR-negative tumors compared to Non-Hispanic Whites . However, in our study we found no interaction between subtype and race .
The protective effect of marriage for survival, that can be explained by patients can gained better economic resources and greater social support in marriage . Although some factors have been found in previous studies, no covariates have been adjusted for other factors, or fewer covariates have been adjusted. We used a Cox proportional regression model by adjusting for all the factors and demonstrated the tumour subtype were prognosis factors. Therefore, in clinical and nursing work, doctors and nurses can carry out different treatment and nursing work for different patients according to age, race, marital status, insurance, tumour grade, histology, subtype, and visceral metastases. In addition, we found that there was interaction between subtype and multiple visceral metastasis, this suggests that we should pay attention to the risk of visceral metastasis in patients with different subtype. Future studies are recommended to explore the mechanism of molecular subtype and metastasis site, but also explore the influence of their interaction on the outcome and management of patients.
We acknowledge that the study has some limitations. SEER database could not know the expression status of ki-67, the ki-67 index value is a prognostic factor in primary breast cancer and is a proliferation marker that also distinguishes between luminal A and luminal B breast cancer . Breast cancer is generally divided into luminal A and luminal B, according to HR\HER2 status and ki-67 in the course of clinical diagnosis and treatment . This may contribute to some disparities between our investigation and clinical applications. We do not have information with regards to radiotherapy or systemic treatments of this cohort, which may contribute to some of the differences observed in survival according to prognostic variables. Addition,the pathological data could not be centrally reviewed and were collected from different local pathology laboratories.