Introduction

The non-communicable diseases are the most common cause of death in the world, and cancer is expected to be the main cause of death in the world in the 21^st century (1). Based on the World Health Organization (WHO) estimates in 2015, in 91 countries of the world, cancer is the first or second cause of death among people aged under 70 years; it is also the third or fourth cause of death in 22 countries (2). Meanwhile, the most common type of cancer and one of the main causes of death among women is breast cancer (3). Although cancer is a global disease, its incidence is significantly different in various countries; it can be caused by such factors as lifestyle, genetic factors, population structure, and environmental factors (4-6). The incidence of breast cancer has increased due to the increasing changes in risk factors (7). According to the report of the American Cancer Society in 2019, 268,000 women were among the new breast cancer cases, of which 41,760 died due to this disease (8). There are substantial geographical variations in breast cancer incidence. According to the GLOBOCAN estimates in 2018, Australia/New Zealand, Western Europe, Northern Europe, and Northern America had the highest incidence rates of breast cancer among women (90 per 100,000 individuals), and Central Africa and South Central Asia had the lowest incidence rates (27 per 100,000 individuals) (2). The incidence of breast cancer is higher in developed countries due to the higher prevalence of the cancer risk factors such as use of oral contraceptives, higher age at first pregnancy, low parity, high-calorie diet, sedentary career, use of HRT (Hormone Replacement Therapy), and alcohol ingestion (2, 9, 10). The incidence and prevalence of breast cancer in Asian countries compared to Europe and the United States are lower. However, the mortality rate is much higher in low-income countries than Europe and the United States. This difference may be related to low breast cancer awareness, delay in diagnosis of disease, lack of access to healthcare facilities, and lack of successful implementation of a national screening program in Asian countries (11-13). In addition, Asia has about 60% of the global population (2). According to the estimates of the International Agency for Research on Cancer, there will be a rapid increase in global cancer cases, and the highest incidence rate will be in developing continents including Africa, Asia, and Central and South America (14). Different studies identified breast cancer as a major problem in Asian countries, including Qatar, Saudi Arabia, Iraq, and Bahrain (15-18), and the average age-standardized incidence rate (ASR) in these countries is 20.4 cases per 100,000 (19). Another study showed that Pakistan has the highest mortality rate of breast cancer among Asian countries (20).

Cancer is the third cause of death in Iran (21). According to the studies conducted in Iran, breast cancer incidence is raising and includes 25% of all cancers (22). In  research conducted on the breast cancer incidence in Iran in 2017, the highest ASR (per 100,000 women) was found in the provinces of Tehran (57.40), Isfahan (51.90), Yazd (48.70), Gilan (48.00), Khorasan Razavi (45.50) and Alborz (47.60) (23, 24). The average age at diagnosis of breast cancer in Iran is about 10 to 15 years lower than in developing countries (25). In addition to the potential risk of death, cancer can have adverse effects on the physical, social, psychological, and economic dimensions, as well as the overall quality of life of patients and their family members. In recent years, Khorasan Razavi Province has experienced the steepest increasing trend in breast cancer incidence (23). Therefore, it is of high importance to pay attention to the epidemiological aspects of this disease for better management and also to make more appropriate plans to prevent it in this province (11, 26). However, few studies have been performed in Khorasan Razavi province in this regard. Different reports can document the potential high-risk areas (areas with a high incidence of breast cancer). In that case, policymakers should take actions for timely diagnosis, prevention, and control of disease in these places. To address this issue, the crucial aim of this study was to estimate and examine the spatial distribution of breast cancer incidence in Khorasan Razavi province between 2013 and 2017.

Materials and Methods

This retrospective record review was performed based on the data recorded in the Khorasan Razavi cancer registration system between 2013 and 2017. This study is a type of clinical research study in which data is collected from the electronic cancer registry database (27). Cancer registration in this province is based on data collection from clinical, pathological, and cytological evaluations as well as death certificates. The data was obtained from the Health Vice-Chancellor of Mashhad University of Medical Sciences after observing the necessary formalities. The method of determining the sample size was full enumeration and all patients who were diagnosed between 2013 and 2017 and whose information was registered in the cancer registration system were included in the study. After refining and coding the data in Excel, the patients’ information were sorted alphabetically for multiple registrations. Then, 1) Patients whose information was recorded only once were included in the study. 2) Patients whose diagnosis date, sex, or age were unknown were excluded from the study. 3) Patients who were registered duplicated were not included in the study.

 In order to collect information, a researcher-made checklist was used and its validity was confirmed by five clinical and epidemiologists. Then, the required data were extracted from the information recorded in the electronic cancer registry database using the aforementioned checklist. Notably, a small subsample (10% of the total sample) was used as a pilot study to check agreement with the previously coded data and to determine the pattern and extent of inaccuracies.

Mean ± SD and frequency (percent) were used to summarize the quantitative and qualitative variables, respectively. All these statistical analyzes were performed by Stata V. 14 and SPSS V. 20 software at the significance level of 0.05.

The ASR was calculated by the direct standardization method using the world standard population. Furthermore, the incidence rates (per 100,000 individuals) were calculated both as a whole and separately for each city of Khorasan Razavi province for each year. Then, the ArcMap V. 10.6.1 software was applied for mapping the incidence rates per 100,000 individuals in the cities of Khorasan Razavi province. as Additionally, the Anselin Local Moran’s I test was used to cluster and outlier analysis or assess the presence or absence of significant geographic differences in the cities of Khorasan Razavi province in terms of the crude rates of breast cancer incidence with ArcMap V. 10.6.1 software. It is notable that Khorasan Razavi province includes 33 cities, and in this study, we had information on 24 cities. 

Results

During the five years of investigation, the total number of identified breast cancer cases in Khorasan- Razavi Province were 5553 cases. As shown in Table 1, the average diagnosis age of the patients was 51.41 ± 12.94 years. The distribution of diagnosed cases based on age groups is illustrated in Table 1 and Figure 1.

Most cases of the diagnosed cases are in the age group of 40-49 years. The same pattern was observed regarding years of under study as well. While the age group of 50-59 years has the highest crude incidence rate per 100,000 individuals. In this study, the crude incidence decreased from 52.50 in 2013 to 38.70 cases per 100,000 individuals in 2017. Also, the ASR between 2013 and 2017 was 54.30, 40.90, 44.80, 42.80, and 40.00 per 100,000 individuals, respectively. In general, the trend of the disease is decreasing during the years under study except in 2015 which observed an increase in the trend of disease (Table 2).

      The zoning of the total calculated incidence rate (per 100,000 individuals) at the level of the counties of Khorasan Razavi province between 2013 and 2017 is depicted in Figure 2. The highest rate of crude occurrence (per 100.000 individuals) was in Bakharz County (149.43) followed by Sarakhas (18.02), Khalilabad (15.71), Torbet Jam (13.91), Chenaran (13.50), Golbahar (13.50), Bardaskan (13.40), Mehvelat (11.81), Fariman (11.15), Roshtkhar (10.71), Kalat (10.09), Khaf (9.61), Zaveh (8.35). Taybad (6.94 per 100.000 individuals) had the lowest incident rate.

     Next, Anselin Local Moran’s I test was applied to assess significant geographical differences, that is to identify significant clusters and outlying areas, at the level of the counties of Khorasan Razavi province in terms of the total crude incidence rate between 2013 and 2017 (Figure 3). Considering the results of this test, no significant cluster was identified in terms of the total crude occurrence rate in the counties of Khorasan Razavi province (P > 0.05). Only the crude incidence rate of breast cancer in Bakharz County was significantly higher than the neighboring counties, which requires more investigation and attention. Also, the crude incidence rate of breast cancer in Taybad County was significantly lower than other counties.

Discussion

This study aimed to estimate the possible geographical distribution of breast cancer in the Khorasan Razavi province. In this study, according to the data related to 5,553 breast cancer patients, the highest incidence rate was related to the age group of 40-49 years and the trend of ASR in this age group was decreasing. The possible reason could be related to advances in diagnostic tools, close supervision, special attention, and extensive healthcare system efforts in recent years. Generally, developed countries have higher incidence rates of breast cancer compared to many low- and middle-income countries (LMICs) (2, 10). The various geographical patterns of breast cancer incidence could be associated with different risk factors and the availability of screening mammography (27). In addition, according to the 2012 report by GLOBOCAN, the ASR of cancer in developed countries was 74.10 per 100,000 individuals and in developing countries, it was 31.3 per 100,000. Also, the highest rate was in Eastern Europe with 96 per 100,000 and the lowest one was in Central Africa with 26.8 per 100,000 individuals (8). In 2020, this rate was reported as 95.5 per 100,000 in developed countries and 26.2 per 100,000 in developing countries, which showed an increase in ASR in developed countries (28). The results of our study are in line with these results. Although in this study, the ASR in 2017 was estimated to be 40 per 100,000 which was higher than the average in developing countries, it was significantly lower compared to developed countries. A 10-year study in Bahrain showed a decrease in ASR during 2000-2010 (18), which is consistent with the results of this study. In the study by Ahmadi et al.  )2018(, the ASR in Iran was 29.88 per 100,000 (29), and in this study, it was higher than the mentioned value, which can be due to the better quality of information registration in the Khorasan Razavi cancer registration system, more comprehensive implementation of screening programs, or a real increase in the incidence. Also, we witnessed that breast cancer was most common in the age range of 40-60 years, which was in line with the findings of Ahmadi et al. (2018) (29). According to the study by Varghese et al. (2018) in the United States, breast cancer incidence increased with age and its peak was in the age group of 55-64 years (30). In the study by Manzouri et al. (2021), the average age for the diagnosis of breast cancer was 41.45 years in Yasouj, Iran (31). A study conducted in China also showed that the age group of 40-45 had the highest number (32).

The main strength of this study is that it is a population-based study, which deals with investigating the epidemiology and geographical variation of breast cancer incidence in the Khorasan Razavi province. This study is of ­ high value and can show the changes in the epidemiological picture of the disease in society. This type of study is precious, especially in developing countries where recording and maintaining data face many problems.

However, the current study had some limitations. 1) Due to the incomplete registration of diseases, some patients were eliminated. 2) The low number of breast cancer cases in this study could be related to failure to identify all cancer cases, missing reports, and the referral of some cancer patients in this province to neighboring provinces. 3) Another critical point was that these studies represented the diagnosed cancer cases each year rather than the actual incidence rate in the same year. 4) Due to the lack of registration of clinical and pathological variables of the disease in the cancer registration system, the present study did not provide any information about the reasons for the observed changes in the incidence of this cancer. All the possible reasons raised in this study are hypotheses that need further investigation in future studies.

Conclusion

The results of our study demonstrated that the incidence rate of breast cancer in Khorasan Razavi Province decreased except in 2015. In addition, Bakharz and Taibad cities have the highest and lowest incidence rates compared to neighborhood cities in Khorasan Razavi province, respectively. Therefore, it is recommended that the responsible authorities take the following measures: promoting the cancer registration system of the province, conducting synthetic prevention, careful evaluation of breast cancer risk factors, performing basic and in-depth clinical studies, reinforcing early detection and screening programs, combining prevention programs, and controlling preventable risk factors, especially in high-risk populations.

Declarations

Acknowledgements

The authors would like to thank all the participants in this research.

Conflicts of interest

Authors declared no conflicts of interest.

Ethical considerations

Patients’ data were obtained after getting the ethical code from the ethical review committee of the Mashhad University of Medical Sciences. Also, all patient information was considered confidential. In addition, the supporting data of the study would be available from the corresponding author upon reasonable request.

Authors’ contribution

A T and M A supervised the study. A K participated in data collection, data analysis, M S and H D assisted with data interpretation. N S assisted with data analysis. All authors have read and approved the manuscript.