Abstract
The objective of the systematic review was to investigate whether breast cancer screening is linked with a decline in mortality rates among women in the United Kingdom. A search was conducted across Medline, PubMed Central, and EBSCOhost databases using keywords “breast cancer screening AND mortality AND United Kingdom.” After applying the relevant eligibility criteria, a total of 13 articles were analyzed. The articles were primarily randomized controlled trials, case-control, cohort studies, and population-based studies. Cohort-based studies indicated that breast cancer screening reduced the mortality rates with a range of 5-25% while cohort studies indicated a mortality reduction of approximately 50%. Population-based studies did not indicate a decline in mortality rates and was explained by the steady state effect associated with the design. Overall, the results suggested that breast cancer screening reduced mortality rates. Therefore, the application of more screening measures could reduce the high mortality and morbidity rates associated with breast cancer.
Keywords: Breast Cancer screening, Mortality rates
The Effects of Early Breast Cancer Screening on Mortality Rates among Women in United Kingdom
Chapter 1: Introduction
1.1 Background of the Study
Breast cancer is considered to be the second leading cause of deaths among women accounting for approximately 570,000 deaths in 2015 alone (Sun et al., 2017). Of the 1.5 million women with various types of cancers, breast cancer makes up approximately 25% of all cases (Sun et al., 2017). Breast cancer is classified as a metastatic cancer and can be transferred to other distant organs including the lung, brain, liver and bone which primarily accounts for its high mortality rates and incurability. Nonetheless early diagnosis of breast cancer leads to a good prognosis and subsequent high survival rates. Mammography screening is the most common approach used in detecting breast cancer (Sun et al., 2017). There are numerous risk factors associated with breast cancer including family history, aging, oestrogen level, sex, unhealthy lifestyles and gene mutations, all of which increase the possibility of developing breast cancer.
Aging is one of the important risk factors associated with breast cancer with incidences showing a direct correlation with increase in age. Therefore, mammography screening is commonly applied to women aged above 40 years. About a quarter of all breast cancer cases are linked to family history. Women with a familial history of breast cancer are more prone to the disease. Using a cohort of more than 113,000 women Brewer, Jones, Schoemaker, Ashworth, and Swerdlow (2017) reported the relative risk of developing breast cancer among women in the United Kingdom with first degree relatives as 1.75 compared to women relatives without the disease. The inherited susceptibility to the disease was primarily linked to two breast cancer related gene BRCA1 and BRCA2. Other breast cancer related genes including Ras, Human epidermal growth factor receptor 2, and Epidermal Growth Factor Receptor (EGFR) have been reported in various studies (Curtis et al., 2012). Reproductive factors such as late age during the first pregnancy, late menopause early menarche and low parity all increase the risk of breast cancer. Both exogenous and endogenous oestrogen levels also increase the risk of breast cancer (Sun et al., 2017). Endogenous oestrogen produced by the ovary as well as ovariectomy reduces risk of breast cancer in premenopausal women. Hormone replacement therapy which involves the administration of exogenous oestrogen has been shown to increase risk of breast cancer (Narod, 2011). Modern lifestyle practices including elevated dietary fat intake and excessive consumption of alcohol also increases the risk of breast cancer. Alcohol consumption elevates oestrogen related hormones which subsequently induce signalling processes mediated by oestrogen receptor pathway. Parkin, Boyd and Walker (2011) estimated that 26.8 cases of breast cancer in the UK was attributable to environmental or lifestyle choices.
Breast cancer affects women with high prevalence rates being noted in women above 40 years as compared to younger women. According to Cancer Research UK (2018) 9 out of 10 women diagnosed with breast cancer are between 40-69 years. Statistics in the UK indicates the presence of 11,400 breast cancer deaths annually. Breast cancer is also the 4th common cause of death within the UK and accounts for approximately 7% of all cancer deaths with high mortality cases being noted in women as compared to men and also among the aged (Cancer Research UK, 2018). The World Health Organization estimates that approximately 627 women died of breast cancer in 2018 which translates to 15% of all cancer related deaths (World Health Organization, 2018). Thus, breast cancer poses a unique health problems to not only the United Kingdom but the world.
Breast cancer prevalence rates increased in the United Kingdom. In an assessing breast cancer prevalence rates in the United Kingdom by the Breast Cancer Care (2015) the disease is emerged as the most frequently diagnosed cancer type. It also represented approximately one-third of all newly diagnosed cancer cases (Breast Cancer Care, 2015). According to the report, more than 55, 000 women are diagnosed with cancer annually in the UK (Breast Cancer Care, 2015). When broken down to the individual countries, the reports that England has the highest prevalence of breast cancer with a total of 42, 000 diagnoses annually (Breast Cancer Care, 2015). It is followed by Scotland which has an annual registration of 4500 new cases of breast cancer (Breast Cancer Care, 2015). Wales and Northern Ireland have fewer annual cases of breast cancer with 2600 and 1300 diagnoses annually (Breast Cancer Care, 2015). It also suggests the presence of over 36,000 cases associated with secondary breast cancer.
A surge in breast cancer screening methods such as mammography has been noted across the United Kingdom. It has been made as an essential assessment by the World Health Organization. Although improvements have been implemented in the assessment and management of cancer of the breast in the United Kingdom in the previous decades, the mortality rates due to the disease remain significant (Stewart and Wild, 2014). Screening trials have been conducted in the United Kingdom for the various types of breast cancer although the effectiveness of each screening method differs. More focus is placed on breast cancer screening as it is the most commonly diagnosed type of cancer among women within the United Kingdom (Cancer Research UK, 2018). This study explores whether breast cancer screening via mammography reduces mortality rates within the United Kingdom.
Breast cancer screening is essential as it provides room to evaluate the patient’s condition and at the same time assess if healthcare goals within the United Kingdom healthcare system especially relating to the reduction of cases of breast cancer are being achieved (Tryfonidis et al., 2015). The on-going screening services breast cancer are efficient in multidisciplinary care in the management of the breast cancer cases and improve patient survival (Marmot, Altman, Cameron, Dewar, Thompson, and Wilcox, 2013). The types of breast cancer screening that will be assessed in the study include the breast self-examination and mammography.
1.2 Problem Statement
Various breast cancer reduction interventions have been developed to reduce incidence and prevalence rates. Treatments aspects currently focus on the selective removal of cancerous cells while diagnostic measures identify tumors which are at risk of becoming benign or cancerous. More emphasis has been placed on early diagnosis as patients can be put on immediate treatment and in the process cancerous cells can be removed. Healthcare teams have become more efficient in diagnosing patients using some of the modern and latest technologies which can identify breast cancer biomarkers in the affected populations. Furthermore, the women who are affected by breast cancer are also actively involved in decision-making concerning their health leading to the existence of patient-centered care with positive outcomes for the patients.
Despite investing numerous resources in the management of breast cancer, high mortality and morbidity rates have been noted suggesting a specific gap in the early management of the disease. According to the Cancer Research UK (2018), the number of cancer deaths in the country in 2016 was 11,563, and this represented 7% of the deaths in the country. These statistics are worrying and indicate that although the country has made modifications the way in which the of breast cancer are managed over the years, early detection through screening remains a major problem. The development of breast cancer also results in psychological distress such as anxiety and depression which can further aggravate the situation, causing suicide in worst cases. Early screening through mammography can help improve patient health outcomes and reduce the number of deaths caused by the disease in the United Kingdom. Therefore, this study explores the importance of early breast cancer screening through mammography in reducing the death rates of the affected women in the United Kingdom.
1.3 Research Aims and Objectives
- Promoting education on breast cancer and enlightening the society on the importance of its intervention in the UK.
1.4 Research Questions
- What are the perceived benefits of early breast screening on mortality rate among women aged 19-39 in the UK?
- What are the benefits of mammography in early breast screening among women aged 19-39 in the UK on reducing the mortality rate?
- What are the benefits of self-examination in early breast screening among women aged 19-39 in the UK?
1.5 Rationale for the Selection of the Topic
Despite the establishment of breast growth examination programs throughout the UK, the death rates due to the disease are still high since many women do not utilize these programs. Many of the women with the disease in the UK present themselves for treatment after they begin feeling abnormalities in their breasts. At this stage, the cancerous cells have already replicated and can only be removed through different treatment modalities which have a range of negative effects on the patients. This topic was therefore selected to provide insight into the most effective mechanisms for reducing mortality rates of women with breast cancer. Although there is increased public awareness on the need for screening, which ensures early detection of malignant tumors, there is lack of public understanding on the effectiveness of the various methods used for screening, especially mammography and self-examination. The topic was therefore selected to determine the advantages of each approach of screening and thereby recommend solutions that can be adopted into policies formulated by the government of the United Kingdom to tackle female mortality due to breast cancer.
The research topic will also help women to know the importance of going for early screening and accessing early treatment to improve their health outcomes. The topic on the benefits of early screening in reducing incidence and prevalence rates of breast cancer mortality rate in the UK is also important to healthcare providers. Unlike the patients, the healthcare providers have a better understanding of the benefits of timely detection of breast cancer through screening. This research will enable them to encourage female patients visiting their clinics and healthcare institutions for different reasons to undergo breast cancer screening as a way of helping to curb the disease in the country.
The results will also be important to the charities and other official bodies supporting the breast cancer initiatives throughout the country. Through this research topic, these organizations will have an in-depth understanding of the importance of prevention through early screening rather than supporting individuals after their health conditions have already worsened due to breast cancer. The findings from this study an also be used by the cancer organizations and the government to launch countrywide campaigns to create awareness on the importance of early breast cancer screening and detection in reducing mortality.
1.6 Layout of the Dissertation
The systematic review research dealing with the effects of early breast screening among women in the UK will be divided into five chapters. The first chapter is the introduction which provides background information, statement of the problem, research objectives, and significance of the study. The second chapter, literature review, deals with a discussion of the positions of the other authors regarding the study topic. The third section presents the methodology which entails the systematic review of the selected existing literature relevant to the topic. The results section reveals the findings of the systematic review including the table of articles and the experimental designs applied. The discussion section provides a detailed evaluation of the findings and supporting them with relevant literature. The last chapter, conclusion, and recommendations, provide a summary of the research and the possibility of conducting future studies.
Chapter 2: Literature Review
This chapter provides theoretical and literature review on breast cancer, its associated mortality rates, and intervention efforts such as early screening methods. The section explores comparative studies derived from journals, reports, government’s reports, and other policy documents that will help shed light into the topic of breast cancer and early breast cancer detection in the United Kingdom’s universities.
2.1 Theory of Planned Behaviour
2.3 Breast Cancer and Mortality in the United Kingdom
Causes of high prevalence deaths from breast cancer are mainly found in cases where the cancerous cells have metastasized throughout the body. Donepudi, Kondapalli, Amos, and Venkanteshan (2014) identifies several systems have been formulated to aid in the staging process of the disease, to determine the severity of the disease. The most common method is the TNM system of diagnosis, followed by the stages ranged from stage 0 to stage 4. One other method used in categorization is the description style, describing the nature and spread of the disease (Donepudi et al., 2014). This part seeks to expound on the TNM staging criteria. The authors believe breast cancer levels can be categorized in any of the five stages: 0, I, II, III, and IV which are further grouped to form eight stages. Strosberg et al. (2016) in support of this notion as it alludes that stage 0 describes the diagnosis in which ductal carcinoma in situ abbreviated as DCIS or cancer which has not invaded other body cells in which cells that are abnormal have been detected and have not yet spread to the nearby breast tissue. Stage I, Stage IA – The stage in which a tumor is smaller than 2 centimeters wide but yet to spread to surrounding breast tissues. In stage IB, the cancer is two centimeters smaller and may or may not form a tumor. The authors proceed to tell that stage IV – This stage, also described as metastatic or de novo metastatic cancer refers to the stage in which a tumor is of any size, and cancer cells have spread to several organs in the body such as the brain or lung
2.4 Early Breast Cancer Screening in the United Kingdom
Since breast cancer affects a huge number of women in the United Kingdom, early screening aids in disease detection, better prognosis, and reduction in mortality rates. Irvin and Kaplan (2014) indicate that different methods have been used in the screening of breast cancer since earliest tests on breast examinations were carried out the 1960s. The most common methods used include mammography, self-breast exams, ultrasound, and magnetic imaging resonance (Irvin and Kaplan, 2014). Mammography is, however, considered as the best method due to its lower costs, high specificity and sensitivity. The United Kingdom has witnessed a substantially high number of women, approximately more than 2 million taking the test (Jenkins, 2016). Of the women screened, only 18 000 had breast cancer, thereby allowing them to receive early treatment. Most women who take part in screening exercises do so regularly, thereby allowing for early detection which improves the chances of success of treatment.
2.4.1 Mammography. Mammography screening allows for preclinical detection of breast cancer tumours while still localized, leading to better disease prognosis. Breast cancer mammography is considered one of the best methods of detecting tumour cells and is supported by scientific studies (Irvin and Kaplan, 201415). One of the recommended mechanisms in the UK Government Policy framework for reducing the mortality rates is the use of screening mechanisms, including mammography (Public Health England, 2017). However, it is notable that there is lack of comprehensive statistics on the advantages of using mammography among women of different age groups. According to The Royal College of Radiologists (2018), there is a 17% mortality benefit from the use of mammography in screening women aged 50-70 years, while those under 50 years cannot be assured of the benefits of mammography. According to the report, mammographic sensitivity at a young age is poorer than at age 50-69.
A study by Mandelblatt et al. (2013) revealed that early cancer screening through mammography reduces the mortality rates associated with the cancer of the breast by 30%. Following the success of these studies, several countries adopted the population-based mammography tests to help in curbing breast cancer. Australia, for instance, achieved the full implementation of mammography screening in 1995.
Women of 49 years and below also attend the breast screening programs which allow for early detection and removal of the cancerous cells thereby improving their health status. Breast cancer screening via mammography is advantageous since it helps in the detection of superficial tumors that cannot be detected using other methods of screening. The use of mammography by oncologists is recommended due to its high sensitivity, thereby making it capable of detecting minute tumors unlike self-examination (The Royal College of Radiologists, 2018).
Irvin and Kaplan conducted a similar study investigating the benefits of mammography in the screening of breast cancer in 2014. This study aimed to establish the benefits of screening of the cancer of the breast through mammography on mortality rates. The researchers analyzed the quasi-experimental research from medical databases such as PubMed, Embase, and Medline on the effects of mammography screening. From the study, it was established that the reduction in death rates fuelled by breast cancer screening through mammography was age dependent. There was a 20% step down in the death rate for the women below 20 years, and 21-22% reduction in death rates among women aged 50-69 years. The study concluded that mammography screening has significant effects on the reduction of mortality rates in women aged 50 to 69 years and insignificant effects in women aged 70 years and above. Compared to the first research, this study focused mainly on the reduction of BC mortality rates through screening in different age groups.
Although mammography screening is widely accepted due to its specificity and detail in breast cancer screening, other studies show that it has a range of disadvantages (Skaane et al., 2013). In a study investigating the benefits and harms of mammography, established that breast cancer screening via mammography results in overdiagnosis. The result is an increased psychological and healthcare burden on the affected individuals. Mammography screening also results in false positive and false negative tests. This study is supported by Houssami, Turner and Morrow (2017) claimed that mammography causes a lot of mental harm to patients especially when they have to seek treatment for problems that have not yet manifested in their bodies. The writer, however, warns that overdiagnosis does not make breast cancer screening worthless and, can be addressed by ensuring changes in screening balance between harms and benefits.
2.4.2 Breast self-examination. Since it is cheaper compared with the clinical breast examination, breast self-examination is most one commonly used method of screening. Most breast tumors are self-discoverable and as such, encouraging more women to undertake the breast self-examination will facilitate early diagnosis and better outcome from treatment. In summary, breast self-examination entails three main aspects: looking by eyes for changes in the appearance of the breast, feeling for any changes in the internal architecture and note the observed changes to be reported to the appropriate healthcare provider.
Mammography screening and clinical breast examination should be used concurrently with the breast self-examination and not used as substitutes. Chen and Li (2015) suggest the International Agency for Research on Cancer which provides information about various forms of cancer concluded that there was inadequate evidence to prove the idea that use of self-examination can be used to minimize mortality rates associated with breast cancer. Therefore, that issue is no longer a controversy as had been years before that study. According to a report by NHS digital, self-examination is unreliable as it fails to detect invasive cancers, which are very small. 41.2 % of women who were screened through mammography were found to have small invasive cancer cells, which they had not been previously able to detect through self-examination (NIH, 2017). Screening by professionals is therefore important in ensuring early detection and treatment of cancer.
2.4.3 Tactile examination. Tactile examination must be done regularly, for instance on a monthly basis. The examination will ensure there is a health analysis of the breast surface to diagnose any condition identified. The examination will start by covering the area below the breast and then proceed to the collarbone (Scoccianti, Rauby-Secretan, Bello, Chajes, and Romieu, 2014). Besides, there will be coverage from armpits to the breastbone and other areas such as the lymph nodes, upper chest, and underarms. According to Scoccianti et al., (2014), every segment of the breast should be examined three times by applying light, medium, and firm pressure on the breast. Detection methods like the wedge section, vertical strip, and concentric circle can all be utilized to achieve the detection of small lumps. During the examination, sensitive palmar pads are placed on the flat inner finger surface and ignited to increase sensitivity in detection. The palmar pads of the fingers are preferred instead of fingertips which are less sensitive. Sometimes long nails at the fingertips can prevent free hand movement. Torre, Siegel, Ward, and Jema (2016) on the other hand has the idea that breast compression between the fingers is also not advisable as one can detect non-existent lumps. When conducting the tactile test, women should look out for texture changes and report to the physician; the presence of a hard knot or any palpable lump in the breast or the surrounding areas like the armpit, any thickening of tissue or unshrinking lump with the next period and any changes in general breast appearance such as size, shape, or symmetry.
2.4.3 Visual examination. Visual examination is conducted with arms relaxed on either side. Hands are then clasped together, the examiner bends to examine breasts. It can also be conducted in front of a mirror where skin discoloration or nipple discharges are noted. Also, any changes in shape and color, and changes in the placement or contour of the breast. Any redness on the breast, prominence of the veins or any skin irritation can signal an increase in blood supply to the breast which is a common sign associated with tumor growth Whelan, Griffith, and Archer, (2006). Sores whitish scales on nipples and ulcers which do not heal properly are signs of breast disease. Additionally, scientists have found an “orange peel” skin which is a swollen and shiny skin with large deep pores. Whelan, Griffith, and Archer (2006)proceed to say that the appearance is due to blocked ducts. Inversion of the nipple or its retraction can be associated with breast disease especially if it is a new development.
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Chapter 3: Methodology
3.1 Study Design and Protocol
The systematic review is designed according to the (PRISMA-P) checklist.
3.2 Eligibility Criteria
The inclusion criteria took into account all research designs including previous systematic reviews, randomized controlled trials, longitudinal studies, and case controls. Government policy papers and reports relating to the rates of breast cancer and their association to mortality rates were also included in the study. All papers relating to breast cancer screening across all populations were also included in the study provided the sample under investigation was over 18 years old. The selected articles used English as the only language and were geographically restricted to the United Kingdom. Articles comparing primary and secondary outcomes within Europe but also reporting on the UK were also included in the study. All selected articles had an element of the primary and secondary outcome. In essence, articles highlighting methods such as the use of digital or film mammography, ultrasonography, breast self-examination, as well as clinical breast examination in relation to mortality rates were included. All the selected articles were also freely accessible. Reviews or designs which only focus on breast cancer screening without providing any information relating to the mortality rates were excluded from the study. In addition, articles on breast cancer screening and its associated mortality rates outside the United Kingdom will also be excluded from the study. The primary outcome of the above systematic review is to check for mortality rates associated with breast cancer.
3.3 Information Sources and Search
A comprehensive systematic search was conducted across a number of databases including Cochrane, Embase, Scopus, Medline, PubMed Central, and EBSCOhost. Only articles published in the last ten years were included in the review. The keywords “breast cancer, screening, AND mortality” were searched across the various databases. The search was also augmented by finding other references lists outside of the aforementioned databases through hand searching of recent reviews. A search of grey literature was also conducted on a number of websites dealing with breast cancer rates in the United Kingdom and was followed by the keywords “author name AND breast cancer screening AND mortality.” PROSPERO databases was also searched to identify any new articles or reviews which were under development.
3.4 Study Selection
Study selection was conducted in a systematic manner to reduce errors and minimize bias in the sample. The study selection involved the use of two independent reviewers who selected studies based on the eligibility criteria- inclusion and exclusion criteria. Any emerging disagreements between the reviewers was resolved by a consensus decision. In instances, where consensus failed a third review became the tiebreaker. The reviewers primarily looked at each of the selected study types and examined their relevance to the research question.
3.5 Assessing Bias
Chapter 4.0 Results
4.1 Study Selection
| Articles found through other different sources (n=0) |
The search returned a total of 4132 out of which 25 met the selected criteria. Figure 1 below indicates how articles were excluded from the study
| Articles identified through database searching (n=4123) |
| Articles found after the search was completed (n=4123) |
| Records screened (n=4123) |
| Records excluded (n=3412) |
| Full-text articles assessed for eligibility to be included in the study (n=711) |
| Full-text articles excluded based on
Abstract only -6 Duplication -2 Full texts not available- 95 No English versions exist- 67 No search strategy- 123 Did not examine selected primary or secondary outcome- 306 Reporting on guidelines alone-99 |
| Study included in the analysis (n=13) |
4.2 Study Characteristics.
Most selected studies provided varying characteristics regarding the study size and other elements. Johns, Swerdlow, and Moss (2018) utilized a nested control composed of a cohort of 959,738 women in both Wales and England. Cases of patients who died from breast cancer from 1991-2005 were matched to controls composed of patients without breast cancer. The risk of breast cancer mortality was then associated with the intention to screen. Odds ratios were then utilized in calculating conditional logistic regression.
Mukhtar, Yeates, and Goldacre (2013) utilized both joint point’s regression analysis and population-based mortality data to analyze whether there was any association between mammographic screening and mortality rates. Data from women who died from breast cancer in England from (1971-2009) and within the Oxford region (1979-2009) was used in the analysis. Specific outcome measures utilized included age-standardized mortality rates as well as age-specific mortality rates. The outcomes were measured over time with changes in the observed trends being noted. Joint point regression analysis was the common method used to show the difference in mortality rates over the years.
Gunsoy, Garcia-Closas, and Moss (2014) utilized a Markov model simulation in investigating effects mammography screening on a women cohort born from 1935-1940. The screening impact on mortality rates and over diagnosis were reported. Key factors are taken into consideration including age range, uptake, and screening frequency. Another study conducted by Johns et al., (2017) utilized an individual based cohort evaluation program targeting the impact of National Health Service breast cancer screening on mortality rates. The sample utilized was composed of women aged from 49-64 who resided in Wales and England since 1991. The study also included uninvited control groups and invited subjects. Breast cancer screening histories were directly linked to individual mortality cases. The paper also investigated the effects of breast cancer over screening
Duffy (2010) investigated the effect of mammographic screening on mortality rates among women aged 40-49. The study was a single arm FH01 arm and was composed of women from 76 centers across the UK who had received yearly mammogram checks. The study also includes women with BRCA mutations. The study compared the FH01 cohort with other two external cohorts. A number of endpoints were examined including status and size of the node, estimated mortality rate based on the Nottingham Prognostic Index (NPI), grade of invasive tumors as well as adjusted differences between the cohort and control groups.
Massat, Dibden, Parmar, Cuzick, Sasieni, and Duffy (2016) utilized a case-control study to evaluate whether mammography screening is associated with increased mortality based on English Breast Screening Program. The study population was obtained from the Cancer registry cases in London composed of patients aged from 47 to 89 years and making a total of 869 cases. The data was then matched to the two general population controls composed of 1642 women without any form of diagnosis to the breast cancer. Cases control matching focused on screening area and date of birth. Regression analysis was utilized to show an association between the various variables.
Marmot et al. (2013) independently reviewed harms and benefits linked with various screening methods focusing on some variables including the relative mortality values as well as incidences of overdiagnosis. The review also focused on the total number of breast cancer cases, benefits, and harms associated with various methods of screening across a number of randomized controlled trials and meta-analysis. Autier, Boniol, Gavin, and Vatten (2011) also reported the effect of mammographic screening in reducing mortality rates in Northern Ireland based on the WHO mortality database and measured age-adjusted deaths via joint regression analysis.
Another randomized controlled trial was conducted by Moss, Smith, Evans, Cuckle, and Duffy (2015) focusing on women aged between 39-41 through the UK breast screening programme units. Interventions and control groups were randomly assigned based on annual screening prior to 48th birthday or date an individual received usual medical care. Breast cancer frequency and mortality rates were compared since through the randomization period with the main outcome measured being death from the disease, breast cancer incidences such as invasive forms of breast cancer and total incidence of breast cancer. Autier and Boniol (2012) also reported on the breast cancer screening rates among West Midlands women aged from 50-64 within the United Kingdom. Breast cancer incidences were estimated over a period ranging from 1989 to 2004 in five different continent databases. Annual percent changes were then estimated through the use of joinpoint regression.
4.3 Risk of Bias within the Studies
Massat et al. (2016) accounted for self-selection bias which arose after women choose not to comply with treatment. Such women had been associated with a higher risk for breast cancer. Apart from self-selection bias, lead time bias which referred to the time taken before diagnosis date and screening exposure was also reported. The two forms of bias were adjusted when calculating the final mortality rates. Johns et al. (2017) also accounted for lead time bias and selection bias. Nonetheless, other biases were also noted in the results including healthy invitee bias which was minimized through scheduling for an invitation through intention to screen analysis. Pre-screening lead time bias was measured immediately observation were made instead of using follow up measurements.
4.4 Results of Individual Studies
Johns, Swerdlow, and Moss (2018) reported that the intention to screen for breast cancer was linked with a 21% mortality reduction. This value was noted in both cohort and case-control analyses although the impact of attendance was slightly greater in case-control investigations compared to cohort studies (36% vs., 32%). Johns et al. (2018) also noted that earlier screening was related to a 47% reduction in mortality rates. Similar studies in the systematic review also noted a reduction in mortality rates of various frequencies after the successful application of a screening program. Massat et al. (2016) noted a decline in mortality rates up by 39% [OR, 0.61; 95% confidence interval (CI), 0.44–0.85]. Further attendance in breast cancer screening measures also reduced the mortality rates by 60 % (OR, 0.40; 95% CI, 0.31–0.51). Johns et al. (2017) also indicated that a reduction in mortality rates from 1991 to 2005 by 21% (RR=0.79, 95% CI: 0.73–0.84, P<0·001) after the application of the English National Breast Screening Programme. This was after adjustments for various variables including lead time, socio-economic status and age were carried out. The results also indicated that breast cancer death rates among individuals who attended the screening process for the first time was 46% lower compared to individuals who never attended the screening process (RR=0.54, 95% CI: 0.51–0·57, P<0.001) and 32 % lower after adjusting for variables such as lead time, socio-economic status and age. Gunsoy et al., (2014) reported a decline in breast cancer mortality by 18.1 % for triennial screening while annual screening within the same range reduced mortality rates by 35%. Duffy (2010) also predicted a significantly lower mortality ratio in the FH01 cohort of 10% compared to the control group 38%.
Marmot et al. (2013) reported on a meta-analysis which showed a relative risk reduction in mortality rates by 20%. Breast cancer incidence rates were reported as 11% when stated as the total share of cancer cases diagnosed. If current estimates were applied directly for every 10,000 UK women aged 50 years and above who were screened within the next two decades, 43 deaths associated with breast cancer would be prevented while another 129 cases associated with either various forms of cancer would be over-diagnosed.
Mukhtar et al. (2013) notes that a decline in mortality cases associated with breast cancer after the introduction of the English National Breast Screening Programme. Mortality rates are indicated to have declines per year for unscreened women aged between 40-49 years and screened women aged between 50-64 years by 2%. Changes in England occurred before screening was done. Thereafter, a descending trend was noted in women below 40 years with the decline in mortality rates being predominant in age group cohorts. Thus, Mukhtar et al. (2013) concluded that population-based mortality data did not show a reduction in mortality rates after mammographic screening within England.
Autier et al. (2011) compared to breast cancer mortality trends across various nations including Northern Ireland through the use of population-based data. A reduction in the number of breast cancer cases by 29% was noted in Northern Ireland after the application of the breast cancer screening. The results indicated that implementation of mammography significantly reduced mortality in Northern Ireland as compared to other countries although the comparisons between the various countries did not suggest that screening had a role in dipping rates of breast cancer mortality. A follow-up study conducted by Autier and Boniol (2012) showed that mammography screening did not reduce death rates. The results suggested an increase in incidence rates associated with lymph node-positive breast cancer from 1989 to 1992 followed by a decrease during 1996 to 2000 and soon stabilized from 1989 to 2004. The results indicate that breast cancer screening program had no role in reducing mortality rates especially in cases where population-based data was utilized.
4.5 Risk of Bias across Studies
Some studies investigated the effects of breast cancer overdiagnosis. In this context, over diagnosis referred to the diagnosis of early-stage tumors which failed to transform to cancerous cells fully. Analysis by John et al., (2017) reported 0.3% cases of over diagnosis which increased to 0.5% of cases were compared to the first 7 screening years. The minor deviations in over diagnosis results were pointed out to one woman invitation tests and were significantly different with other screening tests published under the English National Breast Screening Programme which recorded 10-15% over diagnosis cases. Gunsoy et al. (2014) reported a rate of over diagnosis during triennial and annual screening as 5.6% and 7.6% respectively. Marmot et al., (2013) indicated out of the 307,000 women who were invited to begin screening only 1 % would be over diagnosed in the next 20 years. Marmot et al., (2013) also indicated that several forms of internal bias in trials which had been conducted in the past. Recent observational studies had larger benefit estimates although the results might have been biased.
4.6 Additional Analysis
Massat et al. (2016) performed a sensitivity analysis which allowed for controls to be screened in three years after the first diagnosis to explain for any form of exposure bias which may have occurred while the study was conducted. Out of 252 invitations, 179 individuals attended with the results revealing a 10-15% increase in mortality reduction.
Gunsoy et al. (2014) also conducted a sensitivity analysis assessing the impact of lower and higher uptake of breast cancer screening and included aspects such as 100% screening uptake, 15% reduced screening uptake. 20% reduced sensitivity, 20% increased sensitivity, short and long mean sojourn times. Results indicated that total compliance with screening was linked to a major reduction in mortality as well as over diagnosis whereas partial uptake lowers the aforementioned outcomes. Longer sojourn times increased over diagnosis by two-fold and did not modify mortality reduction while shorter sojourn times reduced both measures. Gunsoy et al. (2014) concluded mortality reduction was dependent on screening frequency, uptake and age range.
Chapter 5: Discussion
5.1 Summary of Evidence
The above results indicate that breast cancer screening primarily through mammography significantly reduced mortality rates with varying frequencies. The difference in the mortality rates points out to the use of different data models, study design, analysis and use of varying populations. Previously studies on breast cancer screening and their association to mortality rates have largely relied on case-control approaches, individual level based data and modeling of aggregated data. In this systematic review most studies relied on the aforementioned methods, and thus, the results could be inferred to other studies. The current results are similar to findings published in recent meta-analysis and reviews investigating the effect of breast cancer screening programs to mortality rates across Europe. The study by Broeders et al. (2012) which calculated mortality rates based on breast cancer screening indicated a decline in deaths by 25% among women who undertook mammography screening. Two other studies conducted in Norway and Finland also reported a decrease in breast cancer mortality rates after mammography screening. Weedon-Fekjræ, Romundstad, and Vatten (2014) reported a decline in mortality case by approximately 25-28% with the study design being similar to study carried out in the UK by Johns et al. (2017). A 28% reduction in mortality rates was associated with women who were invited to screening while a 37% reduction rates were associated with women who regularly attended screening sessions. The greater magnitude in Norway as compared to some of the studies in the UK could be accounted for by the shortened screening time. In Norway, screening is conducted after two years while in the United Kingdom screening based data is present after three years.
The use of different study designs could also account for the differences in mortality rates. Cohort-based designs are considered as non-experimental designs. In utilizing the cohort studies, women are either invited or not invited for mammographic screening although both populations have alike baseline risks for breast cancer deaths and the same opportunities for treatment. Use of cohort-based studies are limited with the expected reduction in mortality rates varying from 10-25% based on a meta-analysis conducted by (Irvin and Kaplan, 2014) . This value is consistent with the results noted by Gunsoy et al. (2014), Johns et al. (2017) and Duffy et al. (2010), which all utilized cohort in their analysis. Case-control studies use cases of women who die of breast cancer as samples while alive women are used as the controls. These studies do not take into consideration whether women were screened for the presence of breast cancer via mammography. Thus when such studies are examined under settings where mammography screening is carried out, the validity becomes low due to the screening of healthy women and selection bias resulting from women who choose to participate in screening but differed with mortality rates with those who failed to participate. Selection bias also occurs when women with breast cancer were not considered as being eligible for breast cancer screening or when screening takes into account healthy women with no history of the disease. Attempts to adjust to some of the aforementioned biases have a direct effect on overall breast cancer mortality rates. The underlying assumption is that the use of the adjustment accounts for the risk of the uninvited women. This could easily be done if the study under consideration was a randomized trial as those not invited in the study and still screened could be considered under the control group. However, since most cases control studies are considered as observational studies where all women are invited for screening, the assumption on the risk of death has to be provided. Such assumptions are rarely examined and are based on estimates. Thus, case-control studies are likely to report varying rates of mortality reduction which are considered as significantly higher compared to other studies. Johns et al., (2018) reported a reduction in cancer mortality rates by 47% after screening while Massat et al. (2016) reported 39% decline in mortality and a further 60% decline in mortality on subsequent attendance to breast cancer screening. Similar studies have reported exceptionally high rates in mortality reduction with a common figure of 50% (Nickson, Mason, English, and Kavanagh, 2012; Hofvind, 2013). A randomized trial conducted by a case-control study in Malmo which had reported a 58% reduction in mortality rates observed an overall reduction of only 4% when the values were standardized for other aspects (Løberg, Lousdal, Bretthauer, and Kalager, 2015). Thus case-control studies tend to overestimate the effects of screening methods on primary outcomes such as mortality.
Population-based studies estimating breast cancer mortality over a period focus on specific geographic areas and age-standardization. In most cases, population-based data is easily available but fails to take into account a number of measures. For example, the annual mortality rate in the population data utilized is never reflective of the time of diagnosis. In addition, population-based data fails to take into account the deaths before the invitation to screen. Furthermore, when all eligible invited women have been screened for a specific period, mortality rates are assumed to have attained a steady state where no further reductions are observed. Population-based data used in the above surveys indicated that breast cancer screening programs did not result in a decline in mortality cases or there were slight variations as indicated in the finding of Autier et al., (2011) and Mukhtar et al. (2013). In the aforementioned studies, the mortality values were either significantly low to associate a decline in mortality rates after breast cancer screening programs had been implemented. These results are consistent with other population-based study findings. Løberg et al. (2015) reviews elaborated on the effect of the Health Insurance Plan study which noted no reductions in the mortality rates. The screening program had been applied for a specific period until the steady state was achieved. Thus, after attaining full coverage within a specific area, it becomes more difficult for population-based data to interpret findings associating breast cancer screening to mortality reduction.
Some studies also reported on the high instances of breast cancer over diagnosis. Ideally, mammographic screening results in a surge in breast cancer cases due to the detection of fresh cases which could have otherwise be diagnosed in later life stages. Theoretically, breast cancer overdiagnosis occurs when a tumor fails to progress to the clinical stage or in some cases regress or death not associated with breast cancer. In the three scenarios, breast cancer diagnosis is commonly followed by treatment without any possible survival benefit. It is possible that overtreatment of breast cancer in over diagnosed cases could also increase the mortality and may serve to explain the no reduction in mortality after screening for breast cancer using mammography.
5.2 Implications to Healthcare Practices
Breast cancer is accompanying with high mortality and morbidity rates across developed and developing nations. One key intervention suggested in reducing incidences of breast cancer is early screening detection, diagnosis, and treatment of tumors before reaching the advanced stages. The above study indicates that early screening is related to a decline in mortality rates. Therefore, there is a need to educate more women on the importance of taking early mammographic screening as well as other tests which could detect the presence of breast cancer. Intervention practices should be applied immediately breast cancer cases are detected to additional reduce mortality rates linked with the disease. Patient education on breast cancer screening methods could be one of the methods used in reducing the high mortality rates associated with the disease. More studies should also be conducted on the effects of various screening methods in reducing the mortality rate. Comparative analysis of the various breast cancer screening methods could provide more clues on the best screening approach in reducing the frequency rates of breast cancer within the UK. In addition, screening measures adopted by other countries such as conducting population-based screening analysis after two years could also be considered within the United Kingdom context.
When conducting future research on breast cancer screening and mortality rates, cohort-based study designs, as well as randomized controlled trials, should be used due to the limitations posed by other study designs such as case-control studies and population-based studies. The latter assumes that the number of cases would attain a steady state and thus a further increase in screening practices would not reduce the mortality rate while the former has high selection bias which results in an extremely high reduction in mortality rate which may paint a false picture of the association between breast cancer screening and mortality rates. It is also important to take into account the effects of overdiagnosis in reporting the association between the above-mentioned variables.
5.3 Limitations
Several limitations are noted from the above study. First, the total number of articles selected for the final review as significantly low. This could be due to the review limitations on using only recently published articles within the last ten years. It could also be due to screening periods in the UK which is done after every three years. Secondly, most of the studies utilized in the review were based on an article with low levels of evidence such as case controls, cohort studies, and population-based studies. There were very few randomized controlled studies conducted in the United Kingdom. Lastly, some of the studies fail to report on methods which were used to adjust for over diagnosis and self-selection bias which may have affected the quality of the results.
6.0 Conclusion
The incidence and prevalence rates of breast cancer are high across most countries. Mammographic screening has been indicated as one of the common approaches which could help in early identification of tumors and the subsequent treatment. The above systematic review conducted by studies in the UK indicates that screening reduces the rate of mortality by various percentages based on the type of study design utilized. Use of cohort-based studies indicates a reduction in mortality rates within a range of 5-25% while use of case-control studies indicated a reduction of mortality rates averaging about 50%. Population based studies indicated that breast cancer screening did not reduce mortality rates although the approach is limited by the steady state assumptions. Overall the results suggests that women above 40 years should undergo mammographic screening in a bid to reduce mortality rates associated with the disease.
6.1 Recommendations
Patient education regarding the benefits of mammographic screening among women aged above 40 years should be utilized to encourage more women to attend early screening. Emphasis should also be placed in increasing the number of screens carried out on an annual basis as screening frequency is associated with mortality reduction. Women at risk of breast cancer should also be taught on the other screening measures which could be applied within their home setting. However, it should be emphasized that the methods do not act to replace mammographic screening which has been indicated as being more sensitive and specific. Another key recommendation would be reformulating the breast cancer population screening program policy. Currently, mass screening for breast cancer within the United Kingdom is carried out of two years. Other countries such as Norway are carrying out mass screening after two years and as a result have more data and information indicating the association between screening rates and mortality reduction. Researchers could use this data to formulate models which can accurately predict the association between the two variables in time and even forecast the effectiveness of different screening approaches. Overall, all of the aforementioned approaches will play a role in reducing deaths associated with breast cancer.
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