In this study, for the first time, we detected the clinicopatholgical characteristics of Tibetan females with BC, whose level of HCS was lower in China as compared to the Han nationality. The results demonstrated that the Tibetan females with BC showed larger tumors (> 2 cm) with frequent T4 stage and later stage (more than a half of III stage). In the exploratory analysis, some clinicopathological characters of Tibetan women with BC may improve in different HCSs.
The current results showed that Tibetan females with BC presented more aggressive clinicopathologic characteristics in the three aspects as compared to the data of Han nationality [24,25,26]. The data of Han nationality were acquired from the seven districts in China or Shanghai, which represented the average or above level of HCS in Han nationality. Firstly, the proportion of small tumor size (≤2 cm) in Tibetans females with BC was lower than that of Hans (7.0% & 25.9%, respectively). Secondly, the proportion of N0 in Tibetan females with BC was lower than that in Hans (22.3% & 47.4%, respectively). Thirdly, the AJCC stage in Tibetan females with BC was usually later than that in Han female (50.5 and 47.3% in AJCC stages III and II, respectively). The differences in clinicopathologic characteristics between Tibetan and Han females with BC were similar to that of the other populations originated from HCS of different levels, such as African-American in the USA, India, and Kenya [14, 27,28,29]. These differences might be attributed to the following reasons. First, the difference in cancer awareness may be one of the reasons as shown previously [28, 30, 31]. TAR is an area about 1.22 million km2 consisting of 71 counties with an overall population density < 3/km2. The main population of this region comprised of farmers and herdsmen . The number of medical technical personnel per 1000 people (unit, person) was 3.03, which was less than that in the East part of China (5.33) in 2012, that is one of the Han habitations . A vast territory with a sparse population and low level of HCS may due to less cancer awareness, which might lead to the delay in early diagnosis. Second, the breast self-examination was lacking for a prolonged period and there was no breast screening until 2009 due to poor HCS. Since 2009, breast screening has been conducted according to the national guidelines of China. Briefly, Tibetan women underwent clinical breast examination, followed by B Ultrasound if abnormal, followed by mammography and biopsy . Thus, clinical breast examination was the main screening tool in the low-income region as it was the most feasible model in these regions. The efficiency of clinical breast examination in the early detection was less than the mammography [13, 28, 29, 31, 33]. Third, other factors such as tumor biology, socioeconomic status, education, comorbidity, may also be the reasons for those differences mentioned before [9,10,11, 14, 15]. Thus, the prognosis of BC could be improved as follows. First, the awareness of BC should be improved through the internet, TV, lectures, visits, experiments, or topic discussions by focusing on the popularization of science on BC. Second, as skin invasion is common in Tibetan females with BC, they should be educated on the method of self-examination, focusing on the breast skin. Third, the doctors in the country should be trained for clinical breast examination. They are the first access for most patients with BC in TAR. The level of knowledge of these doctors might influence the level of diagnosis and treatment in BC.
Then we analyzed the influence of HCS on the characteristics of invasive BC in Tibet. We used HCS and census register as proxy to the SES in our study. The HCS in TAR has improved greatly (shown in Fig. 1) [16, 17, 21,22,23]. The maximal changes in the HCSs may lie in the health expenditures and subsidies by the government. TAR is an underdeveloped region in China, which needs government support, such as HCS. Figure 1 demonstrated great improvement in both aspects of subsidies and expenditure, although the raw data did not consider the influence of spending power, inflation, number of people served, age distribution of the population served, and competing priorities. However, the economic development in TAR was distinct, and the raw data might reflect the trend of subsidies by government and health expenditures in HCSs. Another characteristic of HCS in TAR was the relative stabilization of beds and medical technical personnel per 1000 patients, which differed from that in other underdeveloped regions such as Africa. Several physicians from the latter may migrate to developed countries due to various reasons when they become senior physicians . In addition, several physicians of the Tibetan nationality were trained to serve the patients in their region. Thus, it can be confirmed that the HCS in TAR has been improved greatly in recent years. Also, the influence of HCS on the clinicopathologic characteristics of Tibetan females with BC using age group and census register as the two covariates was detected.
HCS may influence the clinicopathlogical characteristics. The improvement in HCSs can increase the detection rate of patients in an early stage and that in T1–3 tumor, which might be similar to that in Han nationality . We also found the size of the larger tumor (> 2 cm) declined in free HCS, MI combined with a new rural cooperative HCS and a rural and urban integration HCS (data not shown). These may be three reasons. First, the screening of females with BC in TAR encompassed 18.3% (13/71) counties in farming and stockbreeding areas during 2009–2015, which not only helped discover patients of BC in the earlier stage, but also improved health education about cancer. The screening acquainted most Tibetan females in the farming and stockbreeding areas with BC for the first time. Consequently, a large number of BC patients sought hospital help instead of staying at home. Second, the improvement in HCS and traffic convenience allowed the patients to seek hospitalization. In the early time, patients from farming and stockbreeding areas in TAR may stay at home due to low income and traffic inconvenience. Nowadays, patients at a later stage and low income could also go to the hospital for help. Lasha, the political and economic center in TAR, represented the highest level of medical facilities in TAR and was the first preference for most Tibetan nationals. Third, the investment in health care made a marginal contribution . However, the possibility of advanced (metastatic or recurrence BC/IV) stage showed some rising trend in a rural and urban integration HCS, the most recent, improved system. This was an interesting phenomenon. Although the proportion of the patients in early stage increased, we also saw 63% N positive and 27% T4 patients. One would expect a higher proportion of metastatic patients. Those were probably not diagnosed at first presentation due to lack of diagnostic facilties. For example, an inefficient clinical breast exam with respect to the detection of LNM as compared to mammography. Thus, the protocol of BC screening in TAR requires revision. In this revised protocol, health education, breast self-exam, and clinical breast exam were critical, followed by imaging test that mainly focused on the early detection of LNM, and pathological test as the highest diagnosis. Moreover, the duration of screening and the selection of high-risk populations necessitate further revision. As there were so many patients in III and IV stage, we thought the overall management in patients with advanced stage BC might be another key point in improving the prognosis of BC in the rural and urban integration HCS.
Nevertheless, the present study has some limitations. First, we selected Tibetan female patients with BC from TAR people’s hospital to represent the characteristics at presentation of the whole Tibetan population. The enrollment of BC patients in the selected hospital might be biased. However, the selection of this tertiary hospital was based on its ability in the standardization of diagnosis and treatment as well as the influence in TAR . Another selection bias might be ascribed to the underestimation of the cases in the early years. TAR lies in the southwest frontier of China. The incidence of BC was 5.2/100000, based on the data of 2012 , indicating 52 cases annually, while the study reflects < 48.7% of the expected patients, especially for the early years of the hospital. Some patients did not come to the hospital. Second, some information was missing in some cases, which might influence the results. However, we selected relatively complete information for analysis. Third, the present study was a cross-sectional survey from 1973 to 2015 for 42 years. Several common factors such as the use of contraceptives or hormone replacement therapy, number of births, duration of breastfeeding, co-morbidities, and competing morbidities might also influence the results. However, TAR was an anoxic plateau, where only Tibetan nationals resided for centuries in a closed environment. The use of contraceptive and hormone replacement therapy was rare. Furthermore, each family had ≥2 children and all women choose breastfeeding. Altitude sickness was common in Tibetan nationality, especially in males, while this disease might affect slightly in Tibetan women. In addition, the government of TAR provides maximum support in cancer diagnosis and treatment nowadays, such as disease-specific reimbursement. Hence, most patients with BC seek a hospital for help. However, no definite evidence was available on co-morbidities and competing morbidities in the delayed diagnosis in Tibetan women with BC. However, an in-depth study is essential to confirm the findings of this study. In conclusion, the population features in this nationality showed relative stability of the results. Lastly, we did not consider the factors, such as the socio-economic status, altitude factors in different areas, and biomarkers, which might influence the present results. These differences will be analyzed in the following research. However, this was the first cohort study on Tibetan females with BC in TAR, and we adopted stringent selection and evaluation criteria. Taken together, the BC panorama in native Tibetan female, residents of high-altitude in a hypoxia environment, was described objectively.