Breast Cancer Screening Strategies and Indicators in Iran, A Systematic Review

A lot of individual health behaviors and multi-faceted approached have been introduced for breast cancer early diagnosis and prevention. This systematic review aimed to investigate the status of Breast cancer preventive behaviors and screening indicators among Iranian women. In this study, two reviewers included English and Persian articles about breast cancer screening modalities and its indicators in Iran from January 2005 to 2020. English electronic databases of Web of Science, PubMed and Scopus and Persian databases of SID and IranMedex were used. The critical information of articles was extracted and classied to different categories according to the studied outcomes. unrelated studies and duplicated title, abstract and full text of articles, a total of 522 items (225 English and 297 Persian) were included in prevention subgroup. The results of 246 articles about observational and interventional modalities for early detection and methodological indicators of screening were evaluated in the current review. The other categories will be published in a different article. ranged 81-100% (104, 109). Participation rate in the screening program was reported from 3.8% to 16.8% in two studies (53, 110). BC detection rate has been reported in some studies with different designs. In a cross-sectional study achieved on females admitted to the Mammo center of a hospital, BC was detected in 2.3% of 526 screened patients (111). BC detection rate of non-diagnostic mammography in 9395 subjects was 8.5 per 1000 Mammo (112). In BC screening of 26606 females, the detection rate of 24 per100000 was reported in CBE and Mammo evaluation the false-positive detection rate of Mammography was 7.5% in this screening program (113). Sehhati Shafaie conducted a project on 5,000 females referred to BC hospital for screening. They recorded 996 Sono, and 636 Mammo reports with 40 and 183 abnormal cases, respectively and found one BC by performing 14 FNA (114). The screening Mammo rate, diagnostic sonography rate, biopsy rate, and abnormality rate were 27.4%, 26%, 1.4%, and 33% in a screening project, respectively (111). Results of a study indicated that the mean scores of females' breast cancer screening belief and multidimensional health locus of control were 40.72±10.41 and 67.78±17.67, respectively (115).


Abstract
Background A lot of individual health behaviors and multi-faceted approached have been introduced for breast cancer early diagnosis and prevention. This systematic review aimed to investigate the status of Breast cancer preventive behaviors and screening indicators among Iranian women.

Methods
In this study, two reviewers included English and Persian articles about breast cancer screening modalities and its indicators in Iran from January 2005 to 2020. English electronic databases of Web of Science, PubMed and Scopus and Persian databases of SID and IranMedex were used. The critical information of articles was extracted and classi ed to different categories according to the studied outcomes.

Results
A total of 246 articles were assessed which 129 of them were excluded and 114 studies were processed for further evaluation.

Conclusion
This systematic review demonstrated a lot of heterogeneity in population and design of researches about breast cancer early detection in Iran. The necessity of a cost-effective screening program, presenting a proper educational method for increasing women's awareness and estimating screening indices can be the priorities of future researches. Establishing big studies at the national level in a standard framework are advised Background Breast cancer (BC) is the most common female cancer worldwide, representing nearly a quarter (23%) of all cancers in women (1). In Iran, in 2015, the number of breast cancer patients was 12802, and the Age Standardized Incidence Rate (ASR) was 32.63 per 100,000. So, the age distribution of breast cancer compared to its counterparts is low because of its relatively young population. Almost 51% of patients were under 50 years old. It is estimated that about 10,000 women are diagnosed and treated for breast cancer each year (2,3).
Approaches to reduce the global burden of cancer include two major strategies: screening and early detection and active preventive intervention (4). Screening, as one of the most critical early detection methods, has been performed in low-and middle-income countries in only 2.2% of women aged 40 to 49 years (5). The ndings con rmed that the use of screening methods was low in Iranian women (2), and there is no systematic screening strategy for breast cancer in Iran (6).
Screening methods are mammography, Breast self-examination (BSE), and Clinical breast examination (CBE) (7). Although mammography screening was approved as an effective method, a study demonstrated that this method is not cost-effective in Iran (6). BSE can enhance women's awareness, empowerment, and responsibility to their health (8). Results of the previous studies showed almost 60% of females did not know how to perform BSE or didn't have the necessary skills to do it (9)(10)(11). CBE is considered a low-cost method with a broader implement ability that requires no equipment (5). Different factors such as demographic variables, awareness, literacy, social and economic conditions can affect BC screening behaviors (12) which should be considered in planning a cost-effective strategy to control BC in Iranian women. article) and duplication (55 articles). The reason for duplications in this phase was publishing an article in either Persian and English language or publishing an article in two or more journals.
Studies reviewed were classi ed into three categories according to their main themes, including observational (61 articles), interventional (38 articles), and statistical indicators (17 articles). The extracted results of the articles are as follows: Observational studies of BC screening: Among 61 articles of table 1, 56 items were cross-sectional, 3 items were qualitative, and 2 items were survey studies. Most of the studied populations were females referred to HCCs. Some factors in uencing on screening behaviors consisted of HBM components, fear, proactive coping, state of mind and advocacy, educational level, positive BC_FH, family support, awareness, physician recommendation, and age. Four articles had introduced "physicians and treatment staff" as the most important sources of information about screening behaviors (14)(15)(16)(17).
Achievement of BSE by the best estimate varied from no experience to 79.4%. As well as, regular BSE was 4.5% to 47.5%. Performing annual CBE was reported in 4.1%-41.1% of participants, and Mammo had been performed in 1.3%-45% of females. Results of three studies showed 52.9%, 30.9%, and 60% of females, did not know how to perform BSE or didn't have the necessary skills to do it (9)(10)(11). The mean of 5-year and lifetime BC risk perception was calculated 0.89 ±0.89 and 8.87 ±3.84, respectively (18). It was demonstrated that a higher 5-year risk perception had more predictive power for performing Mammo, while it did not predict achieving BSE or CBE. Effect of educational interventions on screening behavior:  Mean_score of A. in the individual education group was higher (P < 0.05).
Mean_score of subjective norms in peer education group was higher (P < 0.05).
No Sig_Dif in mean_scores of perceived behavioral control constructs and behavioral intention between groups (P>0.05) The statistical indicators of BC screening: This category includes the results of statistical studies in the eld of breast cancer prevention (Table 3) , and ASSISTS instrument and model. In two studies, the response rate to BSE and CBE ranged 81-100% (104,109). Participation rate in the screening program was reported from 3.8% to 16.8% in two studies (53,110). BC detection rate has been reported in some studies with different designs. In a cross-sectional study achieved on females admitted to the Mammo center of a hospital, BC was detected in 2.3% of 526 screened patients (111). BC detection rate of non-diagnostic mammography in 9395 subjects was 8.5 per 1000 Mammo (112). In BC screening of 26606 females, the detection rate of 24 per100000 was reported in CBE and Mammo evaluation the false-positive detection rate of Mammography was 7.5% in this screening program (113). Sehhati Shafaie conducted a project on 5,000 females referred to BC hospital for screening. They recorded 996 Sono, and 636 Mammo reports with 40 and 183 abnormal cases, respectively and found one BC by performing 14 FNA (114). The screening Mammo rate, diagnostic sonography rate, biopsy rate, and abnormality rate were 27.4%, 26%, 1.4%, and 33% in a screening project, respectively (111). Results of a study indicated that the mean scores of females' breast cancer screening belief and multidimensional health locus of control were 40.72±10.41 and 67.78±17.67, respectively (115).

Discussion
This paper reviewed the researches in the eld of breast cancer prevention. The studies were assessed and discussed in three themes of observational studies, interventional studies, and statistic indicators as follows: Observational Studies of BC screening: As this time, mammography is the gold standard of breast cancer early detection method. So, it is necessary to specify the status of mammography performance in Iran. In the current study, the range of performing of Mammo between 2005-2020 was 1.3%-45%, while in another systematic review that studied only Persian language articles published in two databases between 2001-2010, 3 to 26% of Iranian females had done Mammo for early detection of BC (12). Although, a study showed that the range of screening methods like Mammo in Iran was lower than developed countries such as the USA, and the UK (53), the results of a screening program in Saudi Arabia resulted to 27.7 % of Mammo achievement (124). One of the reasons of this difference may be due to the lack of a breast cancer screening program in Iran; hence the result reported were extracted from various limited studies with high heterogeneity regarding the study population, sample size, and design. On the other hand, some researches have revealed that Mammo is an expensive modality and not a cost-effective method for BC screening in Iran (6,113), and considering further studies focusing on other screen methods are suggested.
Breast self-examination and clinical breast examination are considered as more available, low-cost, and low-technical requirement screening strategies. Our review study showed that the performance of BSE and CBE ranged between 0%-79.4% and 4.1%-41.1%, respectively, and 30.9%-60% of females did not have appropriate skills to do BSE. Similar to our results, a study conducted on Arab females demonstrated that 69% of subjects did not know how to do BSE (125). According to the current review, low self-e cacy of females in applying screening behaviors may affect on BSE achievement(64). Self-e cacy is one of the most important predictors of screening behaviors (43,45,47,48), and performance of BSE in females with higher self-e cacy is 1.17 times more than others (35). Therefore, it can be concluded that by the improvement of females' self-e cacy, their skills about screening behaviors will also improve. So, education about breast cancer screening methods is worthy of being insisted on by the health system. It may be a more logical strategy for low and middle-income countries in which breast awareness is more bene cial, too. In conclusion, since there is no national study to demonstrate real indicators, most of the current results have been reported from small and limited studies which cause a wide range of affectivity. It seems that more accurate epidemiologic studies are necessary to indicate the frequency of BSE and CBE achievement in Iranian women.
Effect of educational interventions on screening behavior: Effect of various educational modalities on screening behaviors has been studied in different Iranian researches. The in-person method was used by most studies, except for two studies that used telephone counselling. Most of them showed that education was effective in enhancing females' knowledge, attitude, practice of screening behaviors, but no study has revealed which method is more effective in Iran. The population and design of interventional studies varied in different researches, but no study comparing in-person with virtual education was available. Given the growth of using the Internet, it seems that novel technologies like online social networks, applications on smartphones, and virtual learning can be cost-effective methods. Some features of this technology such as more availability, lower price, more users, and offering a more attractive platform, make it a useful modality to be studied in the Iranian population in future researches.
In this systematic review, most educational interventions resulted in satis ed effects (73,76,79,80). It may show that proving educational modalities for breast cancer prevention by the health system is more important than the training methods itself. Selecting a suitable educational method facilitates access to de ned objectives, and it depends on many factors, such as socioeconomic status, health priorities, and cancer preventive policies (126). If early detection of breast cancer is a priority of the health system of Iran, indeed, education programs should be organized as one of the essential correlated factors. On the other hands, promoting the awareness of population induces some diagnostic and treatment demands for BC detection. If we don't provide needed requirements, our health policy goal won't be reached. Related studies in Iran have focused on identifying the educational need of the speci ed Iranian population with different race, culture, income, etc. (80,82,85,87,99,100). So, they can't be generalized to the total population of Iran. Thus, implementing researches at the national level, with more potent methodology and strati ed demographic characteristics are suggested.
The statistical indicators of BC screening: The statistical indicators are one of the most important principles for health policymaking and evaluating the cost-effectiveness of an intervention. They include abnormal rate, detection rate, recall rate, participation rate, etc. According to the extracted results, the BC detection rate in three studies was reported with a different population of the study. One of the studies which were achieved in Zanjan, a city of Iran, 526 women who admitted to the mammography center were assessed. The detection rate had been reported by 2.3% of 526 screened patients (111). In another research was conducted at a tertiary referral university hospital and 9395 digital mammographies performed, and they detected 8.5 cancer patients in 1000 women who underwent non-diagnostic Mammo (112).
The third study was conducted in ten cities of Iran in which over 26,000 women aged 35 and higher, with low socioeconomic status were evaluated. The results showed the detection rate of 24 per 100000 females (113). Although all three studies have reported a detection rate, differences in methodology make them non-integral. The detection rates of invasive breast cancer based on real population screening are targeted >0.5, ≥2.7, and ≥5 per 1000 screens in Canada, the United Kingdom, and Australia, respectively. Also, the detection rates for in situ breast cancer in the United Kingdom and Australia are considered ≥0.4 and ≥1.2 per 1000 screens, respectively (127). The detection rate in Iran has been reported higher than in European countries and even higher than the rate of 2.7 in Asian counterpart countries (128). It seems that one of the reasons for this difference is how females were evaluated which means the reported statistics indicators in Iran were not extracted from a national study and some of them are just the result of limited research in a speci c population. The studied population, the recruited sample size or study design can affect these indices. On the other hand, limitation of detection rate estimation factors like manpower skill, sensitivity or speci city of equipment, and essential resources have not been appropriately assessed in Iranian studies. So, it seems that the evaluation of screening effectiveness in randomized controlled clinical trials at the national level is necessary to reach more accurate information.
Another statistic indicator is the abnormal call rate, which is vital to assess the quality of Mammo image and interoperation. It is de ned as a percentage of abnormal Mammo per number of screens (127). In Iran, it has been reported 28.77% and 33% (111,114). The abnormal call rate for the initial screen in Europe are considered <7 and in all of the countries like Canada, the United Kingdom, Australia, and New Zealand are considered <10 (127). This indicator is related to the recall rate. Recall rate indicates if screening mammography resulted in a recommendation for further imaging or surgical/ clinical visit because of an abnormality on the screening exam (129). The European Guidelines and the American College of Radiology considered recall rate <7% and <10%, respectively, as an acceptable recall rate (129). High abnormal rate induces a high recall rate and increasing the number of unnecessary tests and false positives results (127). According to our result, the recall rate in Iran was 24.7% in total, and for the rst and subsequent Mammo was 29% and 22%, respectively (112). Similar to the previously reported indices, the abnormal call rate and recall rate in Iran has not been extracted from a national screening study. As a result, to determine whether our country needs a breast cancer screening program or not, these indicators must be estimated in the standard and targeted studies, and it is bene cial to be considered as a research priority in health policy system of Iran.
The participation rate represents the percentage of people who participate in a screening program and can be affected by acceptability, accessibility, promotion of screening and the capacity of the plan (127). This index was showed totally 16.8%, 20% in urban areas, and 10% in rural areas of Iran (53,110). The participation rate in screening mammography in Canada, the United Kingdom, Australia, and New Zealand is estimated at ≥70%. The comparison between statistics shows a low participation rate among Iranian women which can have consequences such as reducing the cost-effectiveness of screening programs. It may be due to the low level of awareness in Iranian females, which impacts their attitude towards the importance of breast cancer prevention. Females' attitude can be reformed by the cooperation of mass media such as radio, television or social networks with the health system.
On the other hand, most of the screening costs are paid by patients themselves and may affect their acceptability of some screening strategies and lowers this index compared to the other countries. Some studies have shown that mammography screening is not a cost-effective intervention in Iran (6,113). So, most insurances just support the cost of diagnostic modalities, and the screening tests should be paid out of the pocket. Proving more insurance coverage or accessibility facilities by the health system of Iran can improve the participation rate index.
In this review, we did not nd any study for evaluating the BSE or CBE cost-effectiveness in Iranian population. Considering the importance of those screening methods in limited resources countries, establishing a comparative analysis will provide helpful evidence for policy-makers for early detection of BC in Iran.

Conclusion
This systematic review demonstrated that we have many unknown facts about breast cancer early detection in Iran. It is not clear which strategy is the best. The necessity of a national screening program in a country with a low incidence of breast cancer, presenting a proper educational method for increasing women's awareness and estimating screening indices can be the priorities of future Iranian researches. Establishing big studies at the national level in a standard framework are advised

Availability of data and materials
Not applicable.

Competing interests
The authors declare that they have no con ict of interest.

Funding
This study was a part of a comprehensive project to systematically review the different aspects of breast cancer in Iran. A grant from Roche Company funded the leading research.