Analysis of Breast Cancer Screening Results and Influencing Factors of Breast Cancer in Guangdong Province from 2017 to 2021

Backgrounds Breast cancer screening plays an important role in the early detection, diagnosis and treatment of breast cancer. The aim of this study was to evaluate the screening results and explore the influencing factors of breast cancer detection rate in Guangdong. Methods This cross-sectional study was conducted among 2,024,960 women aged 35–64 in Guangdong Province during 2017–2021. The data about breast cancer screening information were collected from the Guangdong maternal and child health information system. Descriptive statistical analysis was used to explain demographic characteristics and results of breast cancer screening. The generalized linear regression model was applied to analyze the related influencing factors of breast cancer detection rate. Results The estimated detection rate of breast cancer in Guangdong Province is 70.32/105, with an early diagnosis rate of 82.06%. After adjusting covariates, those women with older age (45–55 [OR (95% CI) 2.174 (1.872, 2.526)], 55–65 [OR (95% CI) 2.162 (1.760, 2.657)]), education for high school ([OR (95% CI) 1.491 (1.254, 1.773)]) and older age at first birth ([OR (95% CI) 1.632 (1.445, 1.844)]) were more likely to have higher detection rate of breast cancer. No history of surgery or biopsy ([OR (95% CI) 0.527 (0.387, 0.718)]), no history of breast cancer check ([OR (95% CI) 0.873 (0.774, 0.985)]) and no family history of breast cancer ([OR (95% CI) 0.255 (0.151, 0.432)]) women were more likely to screen negative for breast cancer (P < 0.05). Conclusion The detection rate of breast cancer in screening showed an increasing trend year by year in Guangdong Province. Older age, education for high school and older age at first birth were risk factors for breast cancer detection rate, while no surgery or biopsy history, no family history of breast cancer and no history of breast cancer check were protective factors.


Introduction
Breast cancer is the most common malignancy among women in the world.The American Cancer Society in 2022 depicts that for women, breast cancer in the United States alone accounts for 31% of all new cancer diagnoses [1], as well as in Korea [2].The incidence of breast cancer ranked first in female cancers in China, and there was a dramatic increase in incidence and mortality rates [3].Breast cancer screening, an important method for secondary prevention, is considered as an effective method to reduce breast cancer mortality and incidence rate, and it can also improve the survival rate and prognosis of women with breast cancer [4].The Breast Screening Australia Program showed that screening was associated with between a 30%-41% reduction in breast cancer mortality [5].
Li Wu, Guo-Zhen Chen and Zu-Rui Zeng contributed equally to this study.
In response to the government's call, Guangdong Province launched a free breast cancer screening program for rural women in 2009.In 2020, the screening target expanded from rural women to urban women.Since the inception of the program, the breast cancer screening model has been continuously optimized.At present, the benefits of breast cancer screening have not yet been observed, but the effects may manifest in the future [6].Besides, the pathogenesis of breast cancer is complex, and breast disease is a multifactorial disease.Previous studies have shown that the main risk factors for breast cancer include older age, high body mass index or obesity, exposure to tobacco and alcohol and so on [7][8][9][10][11][12].The risk factors of breast cancer among women in China are different from those in the West, and women in China have unique risk factors for breast cancer [13].Therefore, it is necessary to further explore the influencing factors of breast cancer detection rate in China, and formulate a screening program suitable for women in China [14].
In this study, we analyze the breast cancer screening results and influence factors associated with breast cancer detection rate in Guangdong Province from 2017 to 2021.It can also provide a scientific basis for regulating screening strategies suitable for women and promoting breast cancer screening in China.

Subjects and Study Design
This cross-sectional study was conducted among 2,024,960 women covered by the Guangdong Province during 2017-2021.This study was based on breast cancer screening program in Guangdong province.The inclusion criteria were as follows: 1. aged 35-64 years.2. voluntarily amenable to undergoing breast screening.
The exclusion criteria were as follows: 1. a history of breast cancer.2. pregnant at the time of enrollment.

difficulty in obtaining information.
All the participants provided written informed consent for participation in the study.All study protocols were approved by the Ethics Committee of the Guangdong Women and Children Hospital.

Data Collection
Firstly, the doctors conducted publicity and education on the screening subjects.The information includes basic and clinical information, results of breast examinations, and TNM stages and grades.As the largest province in China, Guangdong has a population of 126.84 million people and covers 17.97 km 2 in the southernmost part of China, including 44 counties.The geographical distribution of screening populations is shown in Fig. 1.

Screening Protocols and Procedures
The screening process included firstly carrying out breast cancer screening education activities for women of appropriate age through community, village doctors or other means.The dedicated person is responsible for conducting a questionnaire survey and provides breast cancer screening.
Question survey: face-to-face inquiry was used to investigate the basic information of the screening subjects, including age, education level, race, menstrual history, family history, birth history and so on.
Breast clinical examination and breast ultrasound examination: all women who participated in the screening underwent breast clinical examination and breast ultrasound examination.The results of breast color ultrasound examination were evaluated by Breast Imaging Reporting and Data System (BI-RADS).
Breast X-ray examination: those who were classified into Class 0 or Class 3 by BI-RADS in color ultrasound examination of the breast were subjected to breast X-ray examination, and the breast X-ray examination results were evaluated and reported by BI-RADS classification system.
Histopathological examination: if the BI-RADS classification result of color ultrasound examination of the breast is category 4 or 5, or the BI-RADS classification result of x-ray examination is category 4 or 5, a histopathological examination (biopsy) will be conducted directly.If the BI-RADS classification result of the breast X-ray examination is 0 or 3, the short-term follow-up, biopsy, histopathological examination or other examinations will be conducted after comprehensive evaluation by specialist above subtropical high level.A schematic of the screening process is shown in Fig. 2.

BI-RADS stands for Breast Imaging-Reporting and Data
System which is a tool for qualitative expression and risk assessment in mammography and breast sonography.According to the diagnostic criteria of BI-RADS of American Radiological Society [15] all participants were divided into the following categories based on the BI-RADS results: a score of zero means insufficient mammography, a score of 1 no problem or lesion, score 2 benign findings, score 3 probably benign, score 4 suspected of malignancy, score 5 clear evidences of malignancy.
In this study, BI-RADS grade 1 and 2 were negative for breast cancer, BI-RADS grade 0 and 3 were suspiciously positive for breast cancer, and BI-RADS grade 4 and 5 were positive for breast cancer.The lesion confirmed by biopsy was breast cancer.Positive cases of breast cancer refer to breast precancerous lesions, breast ductal carcinoma in situ and breast invasive carcinoma confirmed by histopathological examination.

Data Quality Control
The implementation of the screening agency inspectors must qualify, after a unified national special technical training, and training examination.A unified examination process, questionnaire design and reporting methods were adopted during the project implementation.Investigators should receive unified training and finally adopt strict and unified quality control measures.After the investigation information was collected, the data should be confirmed as complete and correct by the quality controller before entering into the database to ensure data quality.Every year, several counties are selected for on-site supervision, review of color ultrasound and breast X-ray imaging data, consultation of difficult cases and timely notification of supervision results.After the completion of screening, the experts in the project group shall 100% reread the uploaded images of breast cancer-positive cases and 1% conduct random inspection for negative cases.

Statistical Methods
R 4.2.1 and Stata 16.0 were used for statistical analysis.Due to the missing ratio of educational level more than 20%, we applied the multiple imputation to interpolate missing values.Descriptive statistical analyses were applied to explain the demographic characteristics and the result of breast cancer screening programs during 2017-2021.Categorical variables were displayed as numbers (%).We described the year-to-year changes in the positive rates of different breast cancer screening methods and the overall breast cancer detection rates, and included the median of the annual detection rates as a continuous variable in the model for trend tests.At the same time, we calculated the rate of early diagnosis of breast cancer each year based on the screening population.We also standardized detection rates based on 2019 census data.Finally, we applied the Generalized linear regression model to analyze the related influencing factors of breast cancer detection.In addition, we created a heatmap to describe the screening population of each city in Guangdong Province.The age trend of breast cancer detection rate was

Population Characteristics
Table 1 presents all participants' general characteristics (n = 2,024,960).The Han nationality of participants accounts for 99.19%, and the education background was mainly middle high school or below (79.47%).The majority of participants were 45 to 55 years old (40.68%).The vast majority of participants had menarche at least 12 years of age (99.32%), and nearly 40% had gone through menopause (38.01%).Few women give birth for the first time younger than 28 (82.74%), and the vast majority of women have a history of breastfeeding (95.52%).Most participants had no history of breast cancer check (75.91%) and surgery/biopsy (98.60%), and had no family history of breast (99.75%) or ovarian cancer (99.92%).

Breast Cancer Screening Results
Breast cancer screening includes clinical examination, color ultrasound, X-ray and pathological examination.Table 2 shows the conditions of these four breast cancer screening programs.The detection rate of each examination showed an increasing trend year by year (P < 0.001).
Table 3 summarizes the results of breast cancer screening in recent years.Between 2017 and 2021, 2,024,960 women were screened for breast cancer in Guangdong Province and 1424 were diagnosed as breast cancer (70.32/10 5 ).Agestandardized detection rate was 30.85/10 5 .There were 462

Influencing Factors of Breast Cancer Detection Rate
Adherence concerning the influencing factors was explored using a Generalized linear regression model.
Age, education, age at first birth, history of breast cancer check, surgery or biopsy history and family history of breast cancer were associated with breast cancer-positive results after adjusting covariates (P < 0.05) (

Discussion
The incidence and mortality of breast cancer, especially in China, increased rapidly in recent years, and breast cancer has become the most common malignant tumor in women [16].The main aim is to detect and modify controllable carcinogenic factors, strive for early detection of malignancy, and thus reduce patient mortality [17].The purpose of this study was to analyze the results of breast cancer screening and the influencing factors of breast cancer in Guangdong Province.

Detection Results of Breast Cancer Screening
Between 2017 and 2021, the main methods of breast cancer screening in Guangdong include clinical examination, mammography, ultrasonography and histopathology.
In our study, the detection rate of suspicious malignancy in breast clinical examination significantly was increased in 2020.It is worth noting that many factors affect the sensitivity of breast clinical examination, such as the experience of clinicians, women's age, body mass index [18].The suspicious positive detection rate of ultrasound examination and X-ray increased consistently, and the positive detection rate of X-ray decreased year by year.Education levels, being older and having a friend who had been diagnosed with breast cancer were also shown to be positively associated with the participation in either mammography or ultrasonography [19].A report from IARC showed that screening women aged 50-69 years with mammography is associated with a 25% reduction in breast cancer mortality [20].Although there is extensive controversy over the pros and cons of X-ray screening, the benefits outweigh the harms of mammography, and the efficacy achieved by screening with mammography is clear [21].Considering the accessibility and relatively low cost of ultrasound examination in clinical practice in China, the guidelines suggest that mammography and ultrasound examination should be combined to carry out screening [22].The pathological examination detection rate of breast cancer among women in Guangdong Province has exceeded 15% since 2020, with a significant increase.Histopathology and other diagnostic methods can confirm or exclude the diagnosis of breast cancer [23].The economy can affect the distribution and availability of health resources, thus affecting the results of breast pathological examination [24].In addition, the ultrasound examination would increase patient's recall rate and opportunities for breast pathology examination [25].These screening methods complement each other.
The breast cancer detection rate reached 70.32/10 5 and increased at almost all age groups by years in these 5 years.The incidence of breast cancer has increased slowly and the distribution of risk factors has been changing [26].Breast cancer screening coverage in Guangdong Province in 2020 was expanded to include both urban and rural women.The sudden increase in the number of women being screened for breast cancer is likely to have an impact on the increasing trend of detection rate of breast cancer.The rate of early detection of breast cancer in 5 years did not change significantly.

Influencing Factors of Breast Cancer Detection Rate
At present, researchers in China have been using the collected information of various risk factors to explore breast cancer risk models [27][28][29].The influencing factors of breast cancer detection rate are still unclear.It is necessary to analyze the influencing factors of breast cancer detection rate using large sample screening data, so as to promote the establishment of standardized breast cancer screening and early diagnosis system in China.
Age is a risk factor for breast cancer, and women aged 45-54 years have the greatest risk of breast cancer comparing to other groups in this study.Women between 45 and 54 years old are in perimenopausal period, and the risk of breast cancer with abnormal estrogen level is higher.After the peak age, the incidence of breast cancer in Asian women began to decline gradually, which is consistent with this study [25].In addition to 45-54 years, there is another age peak for breast cancer onset in China at 70-74 years [30].Most breast cancer screening guidelines recommend mammographic screening for average risk individuals aged 40-74 [31].The main difference between the guidelines is whether to screen women aged 40-49 [32].The age of onset of breast cancer in China is much younger, with a median age of 50 years, and breast cancer is also the most common cause of death in women younger than 45 years [33].
As for the higher education level, we found it increases the detection rate of breast cancer.In agreement with our result, some studies have shown that the level of education is related to health beliefs, and their health beliefs affected breast cancer screening behaviors [34].The higher the education level, the higher the health awareness of women and the more active they will take part in breast cancer screening [35].Some researchers hold different views, they believe that women who have attained tertiary education might be overwhelmed with work schedules and not able to attend or book an appointment for breast cancer screening [36].
The risk of detecting breast cancer in women who are ≥ 28 years old for the first birth is 1.632 times that of women < 28 years old in our study.This increase is due to the late differentiation of breast cells after the first pregnancy, thus increasing the duration of the cancer susceptibility phase.Getting pregnant for the first time before the age of 30 should help reduce your risk of cancer [37].Previous studies have shown that among menopausal or near-menopausal women, the cumulative incidence of breast cancer among women who gave birth for the first time at the age of 20, 25 and 35 (until the age of 70) decreased by 20%, 10% and increased by 5%, respectively, compared with those who had not given birth [38].In addition, the risk of breast cancer in nulliparous women is 1.32 times that of multiparous women [39].
The results of our study showed that no history of cancer check was a protective factor for breast cancer detection.Women who have participated in breast cancer check may have high risk factors for breast cancer, and their awareness of health care is relatively strong, which increases the detection of breast cancer screening.A study, which provided the largest nationwide and population-based self-reported history of breast cancer screening in China in 2015, showed that nearly one-fifth of Chinese women ever had breast cancer screening [40].
In our research results, having a history of breast cancer surgery/biopsy history is a risk factor for breast cancer detection.Current guidelines in China indicate that a history of breast biopsy or surgery for a benign breast disease, or a history of pathologically proven atypical hyperplasia of the breast (lobular or ductal) can be defined as one of the conditions for a high-risk population [41].For women with these above conditions, annual MAM or annual MRI was mainly recommended after diagnosis onward [42].
Family history of breast cancer is an unmodifiable risk factor for breast cancer and have been proposed as criteria for risk stratification [43].Relevant studies have shown that women with a previous benign breast disease or a family history of breast cancer had higher cumulative risks of screening outcomes than women without these characteristics [44].Women exposed to family history of breast cancer can adopt many healthy behavior changes to reduce the risk of breast cancer [45].For example, women should be encouraged to be aware of and to discuss with a clinician.China Breast Surgery Society suggested that women who have the possibility of breast cancer genetic predisposition based on personal or family history should receive genetic counseling [46].

Limitations
Our study had some limitations.First of all, the results of this study cannot be generalized to more developed areas due to the regional particularity of breast cancer screening program.As this analysis is based on a government-led public health service project, there are certain practical difficulties in the implementation process, resulting in the loss of follow-up in all aspects of screening.In addition, our findings cannot determine any causal inference about the relationship between the factors and the detection of breast cancer due to its non-experimental study design.There may be many factors not included in the study, such as screening satisfaction, economic income, body mass index and other important risk factors, which will weaken our final research results.Despite these limitations, this study can provide information that may be useful for both researchers and policy makers involved in public health programs.

Conclusions
In summary, the breast cancer prevalence in Guangdong Province has reached 71.02/10 5 , and it has been increasing from 2017 to 2021.Older age, non-Han, education for high school, older age at first birth, menopause, surgery or biopsy history, family history of breast cancer and never participation in breast cancer screening before are dangerous factors for breast cancer.These findings will provide a scientific basis for China to specify scientific guidelines for breast cancer screening and explore intervention strategies to prevent breast cancer, so that more women can benefit from it.
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Fig. 1
Fig. 1 Geographical pattern of breast cancer screening population in different cities of Guangdong Province during 2017-2021

Fig. 2
Fig. 2 Breast cancer screening process in Guangdong province

Table 1
The characteristics of participants in Guangdong Province from 2017 to 2021 women who had been diagnosed at an early stage, with an early diagnosis rate of 82.06%.breastcancerdetection rate, national standard rate, and the number of early diagnoses have linear trends (P < 0.05).The change of breast cancer detection rate with age in different years is shown in the Fig.3.At almost all age groups, breast cancer detection rates increased from 2017 to 2021.

Table 4
Univariate and multivariate analysis of breast cancer in Guangdong Province from 2017 to 2021