Breast cancer is the most common cancer in women of China, accounting for 15% of all new cancers in women in 2015 [1], and women in urban areas had higher incidences than those in rural areas [2]. In Beijing, the capital and one of the largest cities of China, new breast cancer cases accounted for 22% of all new cancer cases in women between 2008 and 2012 [3]. In recent years, partly due to the changes in reproduction factors (e.g., nulliparity, mean number of children, age at first birth, and breastfeeding), the increasing use of hormone therapy and oral contraceptives, and more westernized dietary habits [4, 5], there were increasing trends of breast cancer incidence and mortality in China [1, 6].

Patient survival is a valuable medical indicator in evaluating the effectiveness and progress of breast cancer control. Stage at diagnosis is a key prognostic factor for breast cancer [7]. The disparities in breast cancer patient survival between Europe and the United States (US) were mainly explained by the lower proportion of advanced breast cancers in the US than in Europe [8]. Furthermore, breast cancer is a heterogeneous disease with distinct biological features, clinical behaviors, treatment responses, and outcomes according to its biological subtypes [9, 10]. However, in-depth analyses on survival have often been single-center studies with limited representativeness of the population [11, 12]. In China, few studies based on cancer registration data reported survival by different molecular subtypes of breast cancer [13].

In the present study, we conducted a multi-center, hospital-based study on breast cancer patient survival in Beijing, China. Meanwhile, using both active and passive follow-up systems of the population-based Beijing cancer registry, we were able to retrieve the information on the exact vital status of the study patients. We systematically analyzed breast cancer patient survival combining information of stage and molecular subtype with a large sample size, which will help us know the influence of related factors on breast cancer patient survival better.

The present study demonstrated the influences of stage at diagnosis and molecular subtype on the survival of breast cancer patients with a large sample size. We found that survival varied significantly by stage at diagnosis and molecular subtype. Patients with late-stage disease had much lower survival rates than those with early-stage disease; patients with HER2 and triple-negative subtype tumors had lower survival rates than those with Luminal A or Luminal B subtype tumors.

The overall 5-year CSS rate in the present study was 90.3%, which was much higher than the estimates around China [16], while similar to those in developed countries. The relative survival estimates were 89.7% in the United States (2007–2013) [17] and 89.8% in Australia (2008–2012) [18]. As one of the largest cities and the capital of China, Beijing has more advanced medical facilities and health resources than most of other cities in China [19]. Patients diagnosed with breast cancer in Beijing could receive better supportive care and expect more favorable treatment outcome. These may all together contribute to the similar breast cancer patient survival rates between Beijing and developed countries.

Stage at diagnosis is a key prognostic factor of breast cancer [20, 21]. In western countries such as Canada, Denmark, Norway, Sweden, and the United Kingdom, about 30.1%–45.2% patients were diagnosed with stage I, 39.0%–47.7% with stage II, 3.5%–15.3% with stage III, and 2.9%–6.9% with stage IV diseases [20]. Our population showed a higher proportion of stage III and stage IV diseases compared with those in European countries such as Norway, Sweden, and the United Kingdom, which may plead for enforced screening program for primary prevention. Considering most of the hospitals involved in our study are tertiary-level medical institutions and a portion of stage IV breast cancer patients diagnosed at relatively low-level hospitals did not receive effective treatment or adopted conservative treatment, the proportion of patients with stage IV disease in the present study may be lower compared with the figure in actual population.

Compared with the reported survival rates in two periods in Beijing, 66.3% (1982–1983) and 74.2% (1987–1988) [22], the survival rate of breast cancer patients was remarkably increased in the present study. The improvement in treatment may contribute to the prolonged survival over the past decades [23, 24]. Besides, with the development of economy and society, citizens may have better awareness on health and early diagnosis of breast cancer. A better stage distribution between 2006 and 2010 compared with those in the past decades may also be an important contributor to the prolonged survival. People living in Beijing are more likely to have high socioeconomic status, to be literal on health, and to have access to good medical service to detect precancerous lesions compared with those in most other cities in China. Precancerous lesions in the breast have visible symptoms with favorable prognosis. An amount of women would go to the hospital when they found palpable masses in the breast. Besides, women in Beijing will easily have access to knowledge on cancer prevention which in turn enhances their awareness on self-exams. Clinical breast examinations, including mammography and ultrasound, are vital approaches to an early diagnosis of the disease. Since 2008, breast cancer screening was performed in Beijing for resident women aged 40–60 years. In addition, since 2011, a biennial breast screening program, free of charge, has been launched in Beijing for women aged 35–64 years [25]. Moreover, awareness campaigns have been carried out in communities in turn to inform and educate people on the disease. It is expected that the survival of breast cancer patients in Beijing would be further prolonged in the future. Breast cancer screening programs have been implemented in developed countries for years [26, 27]. The United States Prevention Services Task Force (USPSTF) recommended biennial mammography screening for women aged 50–74 years and selective screening for those aged 40–49 years [27]. The international agency for research on cancer (IARC) have concluded that breast cancer mortality is generally reduced by screening especially for women aged 50–69 years [28]. However, there is no nationwide breast cancer screening program in China. Chinese women tend to have dense breasts [29], which have low sensitivity and specificity in mammography screening [30]. Ultrasound is a better choice for screening and showed higher efficacy on identifying early-stage patients than mammography from high-risk Chinese women [31]. Moreover, the uneven distribution of health care resources and services make it difficult to carry out uniform screening method in China. Spatio-temporal analysis revealed the cluster pattern for the incidence of female breast cancer, which was useful for a better allocation of health care resources [32]. Large randomized controlled trials of population-based studies are in urgent need among the Chinese population.

Breast cancer is a heterogeneous disease with different molecular subtypes. Our study enabled us to further examine the subtypes of the disease and their associations with survival. The proportion of HER2 subtype in the Chinese population is relatively higher than that for whites in the US, and the proportion of triple-negative subtype is lower than that for African Americans [33], which is consistent with the published findings that the proportion of HER2 subtype was higher in Asian and the triple-negative subtype was more frequent in Black [34].

Significant survival disparities were observed between hormone receptor-positive tumors (luminal A and luminal B) and hormone receptor-negative tumors (triple-negative and HER2). Breast cancer is a hormone-dependent cancer. ER-positive or PR-positive tumors account for the majority of breast cancers diagnosed. The survival differences among patients with various molecular subtypes of breast cancer reflected the distinct treatment responses associated with different expression statuses of hormone receptors. Tamoxifen and aromatase inhibitors are routine drugs for hormone receptor-positive tumors, and patients with HER2-overexpressed tumors can be treated with trastuzumab [35–37]. Triple-negative tumors can only be treated with surgery, radiation therapy, and/or chemotherapy [38]. Survival of patients with HER2 subtype disease was similar to that of patients with triple-negative subtype disease in the present study. The reason may be due to the insufficient use of targeted drugs for patients with HER2-deficient tumors [39]. The targeted drugs can be a large financial burden for the patients and are not covered by the basic medical insurances for urban residents and the new-rural cooperative medical system insurance in Beijing. Furthermore, not all HER2-positive breast cancer patients can benefit from trastuzumab therapy [40]. Therefore, the improving health insurance coverage may be needed. More advanced therapies and health care policies on HER2 and triple-negative molecular subtypes are of great importance.

BMI and histological grade are significant indicators associated with breast cancer patient survival apart from stage at diagnosis and molecular subtype, which had been reported in previous studies [41, 42]. Application of BMI and histological grade in the clinical practice can help clinicians predict the prognosis of breast cancer patients. Besides, relative studies showed that early age at menarche, late age at menopause, nulliparity, late age at first birth, and limited breastfeeding were also associated with increased risk of breast cancer in Chinese [43]. Activities on promoting the awareness of risk factors in women may improve the cognition of breast cancer, which could help women in risk pay more attention on cancer detection or recognize the disease in early stage.

The Beijing cancer registry was established in 1976, which has a long history and good working basis on cancer incidence and mortality registration in China. Considering some breast cancer patients were lack of effective treatment in the population, the 5-year CSS rate in Beijing in the present study may be higher than that of population-based estimates. However, the multi-center nature of the study enables an inclusion of about 40% of the total patient population, which leads to a fair degree of external generalizability of the survival estimates of patients with breast cancer at different stages and of different molecular subtypes. Hospital-based cancer registration can provide extensive, detailed, and reliable information on clinical characteristics. As hormone receptor status and cancer stage are not routinely required by registries, limited high-resolution survival researches in China hindered the cognition of breast cancer and the development of its treatment. This study can help explore hospital-based cancer registration pattern, assess data accessibility, and provide basic information for evidence-based medicine.

The present study demonstrated the influences of stage at diagnosis and molecular subtype on the survival of breast cancer patients with a large sample size. Stage at diagnosis and molecular subtype are independent prognostic factors associated with breast cancer patient survival. Patients with late-stage diseases had much lower survival rates than those with early-stage diseases, and patients with HER2 or triple-negative subtype tumors had lower survival rates than those with luminal A or luminal B subtype tumors. Cancer screening is encouraged for the early detection and early diagnosis of breast cancer. More advanced therapies and health care policies are needed on HER2 and triple-negative subtypes. Our study can also provide basic information for clinicians and policy-makers in further actions on breast cancer treatment research and health care and serve as a baseline for the establishment of hospital-based cancer registration system.