DO AROMATASE INHIBITOR CAUSE COGNITIVE DYSFUNCTION IN BREAST CANCER PATIENT? Abstract The

DO AROMATASE INHIBITOR CAUSE COGNITIVE DYSFUNCTION IN BREAST CANCER PATIENT?
Abstract
The aromatase inhibitor is considered the most essential component for treating majority of the post menopausal women, possessing a positive hormone receptor, and a commencing phase for breast cancer. However, the endocrine therapy also has a positive role in developing cognitive disorders. Estrogen can also assist in increasing the cognitive functions with the help of different mechanisms. The glutamate neurotransmitter and cholllinergic system also helps in elevating these types of functions with the help of several mechanisms. The patients suffering from breast cancer is considered to be among the highest group of individuals surviving with cancer for a prolonged duration of time.
Third chapter is based on the results of the dissertation and this chapter focusing on the activity of the aromatase inhibitor and this chapter also gives brief discussion on mode of action of the aromatase inhibitor. On the other hand, side effect of AIs is the most important issue of this treatment. Thus, chapter three also focus on the side effect of the AIs. However, Estrogen is the most common hormone, which is responsible for developing breast cancer in the women thus this chapter also briefly, described the biosynthesis process of estrogen and function of estrogen in developing breast cancer. Chapter five is based no the discussion and conclusion and this chapter is based on the brief analysis of the findings and provide a brief con conclusion based on the findings of the research.
Table of Contents
Chapter 1: Introduction 4
1.1 Introduction 4
1.2 Background of the research 4
1.3 Gap in the previous researches 8
1.4 Research rationale 8
1.5 Research Aim and objectives 11
1.6 Research Question 11
1.7 Research significance 11
1.8 Structure of dissertation 12
1.9 Summary 14
Chapter 2: Methodology 15
2.1 Research method 15
2.2 Data collection 15
2.3 Data analysis 16
2.4 PRISMA diagram 16
2.5 Boolean search table 17
2.6 Exclusion and inclusion criteria 18
2.7 Ethical consideration of systematic review 18
Chapter 3: Results 20
3.1 EE complex formation is important for the functioning of aromatase inhibitor 20
3.2 Aromatase inhibitor works effectively at the early stages of cancer development with additional side effects and symptoms 20
3.3 Estrogen biosynthesis is the main area of effect for Aromatase inhibitors 21
3.4 Aromatase inhibitors are effective in treating cognitive dysfunction 23
Chapter 4: Discussion and conclusion 25
4.1 Discussion 25
4.2 Gap in research and future prospects 26
4.3 Conclusion 26
References 29
Chapter 1: Introduction
1.1 Introduction
It has been analysed that there are several cases that can give rise to breast cancer. It has been manifested that several therapies for treating of breast cancer has been brought into the market. However, there is no such specific treatment except chemotherapy that cans minimize the growth of breast cancers and cognitive dysfucntioning. In this study the treatment of breast cancer with Aromatase Inhibitors has been discussed and the cases that deal with such cases are being mentioned. The present chapter of the research introduces the main topic of the research. The chapter aims at discussing the background of the situation. However, the problems arising out of the cognitive disorder out of the treatment of breast cancer patients is also highly a matter of discussion that has been discussed in the research. This chapter also sets the aim and objective of the research. The aim of the research is based upon the gap in the study by the previous researchers. The research aims to study the gaps that were not studied previously by the other researchers. The chapter also defines the purpose of the research and why the research is important in the current context. A discussion regarding the background situation that makes the discussion of the research important is the main importance of the chapter. This chapter of the introduction presents an overview of the problems that are associated with aromatase inhibitors in the treatment of breast cancer.
1.2 Background of the research
The Aromatase inhibitors are regarded as the most crucial component in the treatment for the majority of post-menopausal women having hormone receptor-positive, an early-stage breast cancer. Based upon the researchers it is seen that the patients taking Aromatase inhibitors experience a very low level of oestrogen circulation. This may lead the female patient to experience a result in cognitive dysfunctions. This establishes a relation between oestrogen and cognition. There are various complaints of memory loss and thinking that the researchers have witnessed among the survivors of breast cancer. At first, the cause for such a problem was attributed to chemotherapy. However, recent researches have established the fact that there is a potential role of endocrine therapy in cognitive disorders. The most common therapies of endocrinology that are mostly implemented for the treatment of breast cancer are tamoxifen and the aromatase inhibitors that comprise anastrozole, exemestane, and letrozole. Tamoxifen is responsible to bind the receptors of oestrogen and has mixed properties of agonist and antagonists depend upon the target tissues. On the other hand, the major responsible factor for lowering the level of circulation of oestrogen is aromatic inhibitors. This is possible by converting androstenedione to estradiol within tissues named adipose.
Based upon the clinical trials, it has been regarded by the researchers that the aromatase inhibitors are comparatively more superior to tamoxifen in treating at the early stage of breast cancer. However, researchers have also found out that there are some of the side effects of involving aromatase inhibitors. The adverse effects may be a potential effect on the cognitive functions that are being discussed in the research. This part of the chapter provides detailed information regarding the cognitive disorders that is caused by the effect of AI on the treatment of the breast cancer. The discussion regarding the background gives a detailed explanation from the study of the previous work of the researchers. The previous researches as well as the results give an indication that the AI is responsible for the cognitive disorders. Several techniques are being used to treat cancers and also it shows huge side effects in the body of the women. It can thus be stated that the Aromatase treatment can be effective in terms of proper method.
Preclinical data depicting the role of oestrogen and the cognitive function
There is basically much evidence that supports the importance of oestrogen in cognitive functions. As per the opinion of Razaviet al. (2020), the receptors of oestrogen are basically found in the areas of the brain and are regarded as very crucial in cognition that includes the hippocampus, prefrontal cortex as well as amygdala. Oestrogen by the means of various mechanisms can enhance cognitive functions. The “cholinergic and glutamate neurotransmitter systems” are the two most crucial for regulating the memory as well as learning activities that are enhanced by oestrogen.
Figure 1.1: Estrogen in the process of enhancing cognitive functions
(Source: as influenced by Razaviet al.2020)
As per the views of Franiket al. (2018), it can be said that estrogen increases the plasticity of neurons and implies a considerable impact upon “serum lipid profiles” by decreasing “low-density lipoproteins and increasing high-density lipoproteins,” that might reduce the enhancement of “cerebral atherosclerosis” and hence the cognitive decline can be prevented. However, based upon the views put forward by Khosrow et al. (2020), it can be said that there exists a negative effect of estrogen on the functions that are cognitive and complex. The functions might be based on the underlying health of neurology at the time of exposure to estrogen.
Clinical base of Aromatase inhibitors (AI) and cognitive function
As per the opinion of Goldvaseret al. (2018), it can be regarded that despite the prevalence of aromatase inhibitors in treating breast cancer there are only a very few studies that evaluate the impact of aromatase inhibitors on cognitive functions and that is the main reason that they are conflictive. The literature that relates to the function of AIs on cognitive function can be regarded to be very complex having positive, negative, and absence of effects that have been observed in a wide variety of experiments. Augusto et al. 2018 are of the opinion that there have been many comparisons between the women that are prescribed to take AI with the others that have been prescribed not to take AI. Based upon the observations that the researchers have done, it can be conferred that the women who had taken AIs along with the tamoxifen are consistent with the idea that the AIs have a very little effect or a negative effect on the cognitive functions. In the majority of the cases, it can be seen that the negative results can be attributed to the lack and the potential compounds of the experiment.
A lot of women whose age ranges from 21 to 65 that received an AI have reported being having cognitive problems than the controls. Thus based upon the views put forward by Mills et al. (2018), it can be regarded that the anticancer therapies may to some extent deteriorate the cognitive functioning that affects the functioning and the psychological well-being of the patients. In this study, the premenopausal and postmenopausal patients received “adjuvant endocrine therapy” (ET). tamoxifen with or without LHRH analogue or aromatase inhibitor has been mainly used as the treating compounds. The study is done based on the results that have been obtained. Neither of the dissimilarities has been found pertaining to “anxiety, depression or QOL measures either”. “Baseline cognitive test and QOL” results have been associated with later anxiety and depression.
Breast cancer patients have been regarded to be representing the largest group among those that are surviving cancer for a long period of time. The curative therapies have been provided to the patients and a result of which there has been a suspicion of the adverse effect of the treatment. The predicted adverse effect of the AI treatment comprises the effect on cognitive functioning. Based on the opinions put forward by Pistelliet al.(2018), it can be regarded that the researchers have found that the adverse effects have been found in the areas of thinking, reasoning, verbal memory, and executive functioning, concentration, psychomotor speed as well as verbal fluency.
As regarding the side effects of chemotherapy Hershman et al. (2018) is of the view that is related to cognitive deterioration is referred to as the chemo brain. Various studies have been done on the basis of the treatment by AI. The results of the studies have found that a long-term therapy of AI may cause significant cognitive deficits as compared to surgery or other treatment methods. However, the most important part is that endocrine therapy varies from age to age. Based on the age factor the status of risk varies.
In the case of breast cancer, the patients, when administered drugs like tamoxifen or aromatase inhibitors, dramatically alter the amount of estrogen that is available in their body. There may be cases that a patient may be less affected by the chemotherapy but have a greater effect from the endocrine therapies. This varies from person to person and from age to age.
Aromatase inhibitors
Aromatase inhibitors are regarded to be the compounds that are administered to stop the production of oestrogen in postmenopausal women.
According to the views put forward by Pineda et al. (2020), it can be recognized that Aromatase inhibitors perform the work by blocking the enzyme aromatase that turns the hormone androgen into a small quantity of oestrogen into the body. This signifies that a very less amount of oestrogen is available for the stimulation of the growth of the “hormone receptor-positive breast cancer cells”
As per the opinion of Khosrow et al. (2017), it can be rightly said that the most common AI that is used are the Arimidex, Aromasin, and Femara. The medication involves a pill that is taken once a day. The reason is that since the AI cannot stop the ovary from making oestrogen, they are used only in the treatment of postmenopausal women.
The benefits of Aromatase inhibitors comprise the following.
Firstly, the aromatase inhibitor is regarded to be the most effective therapy in treating cancer at the early stage. Secondly, the intake of AI prior to the taking of tamoxifen for a time period of 2-36 years yields more benefit than 5 years of tamoxifen. Thirdly, taking an aromatase inhibitor for 5 years after taking tamoxifen for 5 years persists to increase cancer to relapse. This is not the same in the case of treatment with AI. Research carried on 69 women, who had undergone chemotherapy and five years of aromatase inhibitor therapy. Women were being treated with only aromatase inhibitors for five years and women-only going through chemo. 25% of women had secured a low score on the test as compared to the initiation of the research (Khosrow et al. 2017). And after nine months 35% of the women had obtained a low score in the test. Researchers conducted a hormonal therapy with the help of a mathematical formula that gave the result that hormonal therapy is the main cause of the cognitive problem.
1.3 Gap in the previous researches
The research papers of the previous researchers analysed the cause of the cognitive problems among breast cancer patients. However, the cause was not fully analysed. This resulted in further research. As per the opinion of Del et al. (2020), the basic difference between the effect of chemotherapy and hormonal therapy has been mostly confused and is often very difficult to analyze. Added to this what posed to be a problem is that the results and the effects of the therapies vary from person to person. Even age continued to play a very crucial role. Thus, based upon the confusing result, the researchers could not come to a conclusion regarding the effect of AI on cognitive dysfunction. The effect of AI has not been studied well by researchers. The impact of chemotherapy on the patients has been analyzed to a greater extent. It is only a new trend that the aI has been given importance. Thus, the researchers could not obtain a proper result. The gaps of the previous researchers comprise the lack of the proper research area and the fluctuating results that often tended to make the researchers come to a conclusion very difficult.
1.4 Research rationale
Aromatase inhibitors are one of the most important components for the treatment of breast cancer. During the early stage of breast cancer, most postmenopausal women are hormone receptor-positive. Nowadays breast cancer is one of the most important threats for women. Thus, aromatase inhibitors are the most effective treatment for breast cancer. On the other hand, there are several negative impacts of aromatase inhibitors on cognitive function. As per the view of Baker et al. (2018), aromatase is one of the most important and responsible for the production of all endogenous 17β-estradiol (E2). However, E2 is generally found in both male and females and E2 plays an important role in brain development and maintains different kinds of cognitive reactions. Thus, it can be said that E2 is essential for the development as well as the growth of every species. However, in the case of females during breast cancer treatment all people received chemicals but in the case of breast cancer females are taking chemicals such as aromatase inhibitors and this is the most important cause of conductive dysfunction.
According to the view of Biro (2019), during breast cancer treatment aromatase inhibitors suppress the conversion of androgens to oestrogen and the suppression of aromatase inhibitors lead to t5he different kinds of disorder. However, cognitive dysfunction is one of them. Besides the cognitive dysfunction, E2 is essential for brain development in the early stage and this is important for recovery from brain stress as well as different kinds of brain injury. In the case of aromatase conversation, the aromatase transfers into the androgens in the different regions of the brain. Thus, this affects the brain and this is one of the most important causes of mental health problem. On the other hand, oestrogen is one of the most important hormones for females and oestrogen plays an important role in neuronal plasticity. In the case of breast cancer treatment, Aromatase inhibitors affect the function of the brain and this is one of the most important causes of the decline in the neurological process. This leads to oestrogen exposure. According to the view of Hartman et al. (2018), the decline in the neurological process and oestrogen exposure is the most important cause of cognitive dysfunction.
The aromatase inhibitor is one of most important treatments for breast cancer but the side effect of the aromatase inhibitor is the most important threat for the female during the treatment of breast cancer. However, aromatase inhibitors are the most important for brain development as well as important for the development of different kinds of hormone receptors. However, a big amount of AI is one other important cause of neurological problems and adverse use of AI is the cause of estrogen exposure. According to the view of Parsons and Dietrich (2019), oestrogen exposure leads to different kinds of conjunctive disorder and leads to cognitive dysfunction. Cognitive dysfunction and disorder are the most important threat for both male and female. This is one of the neurological problems for women and this one of the important causes of the mental health problem. Moreover, Alzheimer’s disease is the most common cognitive disorder and this is the cause of cognitive dysfunction. Moreover, AI is important for brain development in the early stage. According to the view of Yang et al (2019), Due to the aggressive AI conversation, there are several neurological problems occurring in the brain and this leads to a developmental disorder.
Nowadays, most females are facing several problems after taking breast cancer treatment with AI. As per the view of Pondéet al. (2020), due to the cognitive disorder, most of the females in the UK are suffering from Alzheimer’s disorder. More than 5 million females in the UK are facing this problem. Moreover, most of the females lost their short term as well as long term memory due to the effect of cognitive dysfunction. However, confusion, poor motor coordination, impaired judgment and identity confusion is the major problem facing by female patients due to the side effect of the Aromatase inhibitors. According to the view of Underwood et al (2019), emotional imbalance is the most important problem and cognitive dysfunction is one of the most important causes of the emotional imbalance. However, due to cognitive dysfunction, most of the females are feeling frustrating. Besides the mental problem, most of the females are facing several physical problems such as loss in motor coordination and facing several neurological problem and physiological cognitive disorder. According to the view of Wilkinson and Boutet (2020), cognitive dysfunction or cognitive instability have various long term, as well as short term effects and all these, lead to one of the major threats for the female after taking breast cancer treatment.
The current study sheds light on the effect of Aromatase inhibitors after taking breast cancer treatment. On the other hand, this study also focused on the effect of AI on aromatase dysfunction. As per the view of Wirtz and Baumann (2018), most females in the UK are facing several problems after taking breast cancer treatment. Thus this research focuses on whether AI is responsible for cognitive dysfunction or not. On the other hand, this research focused on the different side effects of Aromatase Inhibitors. Moreover, this research focuses on the different kinds of cognitive dysfunction responsible for different kinds of disorders.
1.5 Research Aim and objectives
The research aim is considered to be the founding pillar of the research. The research aim serves to be the first step towards the progress of the research. The aim of the research clearly states the framework or the topic based on which the research is done. As regarding the present research, the research aims to study the possibility of cognitive dysfunction that is caused by the administration of the Aromatase inhibitors upon the patients suffering from breast cancer.
As regarding the objectives of the research, the present research has the objectives of following.
To identify the therapies in order to cure breast cancers
To evaluate critically the use and effects of aromatase inhibitor in curing breast cancer
To analyse the role of aromatase inhibitor at an early stage of breast cancer
To analyse the contribution of an Aromatase inhibitor in the cognitive dysfunction.
To compare aromatase inhibitors is more likely to be most effective therapy unlike any other therapy in breast cancer
1.6 Research Question
The questions of the research are dependent on the aims and objectives framed in the chapter. The research questions play a very crucial role in the completion of the research. The research questions are basically the guidelines upon which the research is based. The answers that the research the questions of the current research are as follows
What are the common treatments available for breast cancer?
Why are the Aromatase inhibitors considered to be a very useful and effective method of the treatment of breast cancer?
What role do the Aromatase inhibitors play in the curative process of early breast cancer?
How do Aromatase inhibitors contribute to cognitive dysfunction?
Can the Aromatase inhibitors be considered to be an effective treatment of breast cancer than surgery or chemotherapy?
1.7 Research significance
The significance of the research gives the importance of the research. The topic is a very highly sensitive one as there is a great rise in the breast cancer patients. Previous researches have seen that there is a greater increase of the side effects of the treatment that the breast cancer patients symptomise. As per the opinion of Raptopoulos and Constantinou (2020) it can be said that the side effects pertain mainly to the memory and the logical reasoning problems. Now it is very important to determine where these symptoms develop in the patients. The process of the investigation led to the administering of the AI on the patients.
The AI is responsible for the blocking of estrogen hormone as the estrogens are regarded to protect the enhancement of the tumours. The patients on the other hand fail to recognise the consequences of the treatment and it is sometimes very confusing to the patients also as to which therapy to choose. The chemotherapy also possesses many of the lifetime symptoms. The AI has been historically ignored as a result of which the impact of AI upon breast cancer patients are of varied length and dimension. As per the opinion of Martino et al. (2020), it can be said that the significance of the research is to this extent that it helps the women to understand the adverse effect that the treatment procedure can adversely affect their life. The dark side of the treatment with Aromatase inhibitors upon the treatment of the cancer is the main purpose that the study mainly focuses on. Thus the research also gives prime importance on the development of the alternative treatment procedures to AI and chemotherapy.
1.8 Structure of dissertation
The structure of the dissertation gives a clear overview of the structure that the dissertation process goes through. The dissertation is totally divided into a total of 5 chapters that discusses the various aspects of the topic.
Figure 1.2: Structure of the Dissertation
(Source: as influenced by Martino et al.2020)
The first chapter of the research dissertation is Introduction. This is the chapter that introduces the topic to the viewers. The introduction chapter introduces the basic elements of research and the keywords that are used in the research. The key ideas behind the research are the thing that has been described in this chapter. The introduction of the dissertation provided the aim and objectives as well as the background of the research.
The second chapter is the literature review. The literature review is the chapter that discusses the work of the previous researchers whose research works have been taken for review. The idea is to present the viewers with the basic overview of the topic and its importance.
The third chapter is the research methodology. This is the chapter that gives the detailed overview of the methods that have been adopted in the research in obtaining the results for the discussion in this research. The research involves a primary data for the analysis of the results. The data has been collected from the patients who have been diagnosed with AI for the treatment of breast cancer.
The fourth chapter that the research work comprises is the results and discussion. The result is the obtained outcome from the data collection in the previous chapter. The result that is obtained in this chapter is carried forward in the next section of the chapter where the interpretation of the result takes place. This is the discussion section where the themes are being developed and based on the themes the result has been interpreted.
The final chapter of the dissertation is the conclusion and recommendation. The conclusion gives a concluding statement as well as the validity of the research. On the other hand, the recommendation section gives the further chance of improvement and the suggestions that the researcher can provide based upon the research results. The recommendation is solely based upon the researcher’s understanding of the result that has been obtained in the report.
1.9 Summary
Based upon the discussion made in the chapter it can be summarised that the identification of the AI as the main element that causes the cognitive dysfunction among the patients undergoing breast cancer treatment. The AI is regarded to be the main causative element of the cognitive disorder. Based on the discussions made in the background section of the chapter, the aim of the research has been ascertained to identify the cause of the cognitive disorders and dysfunctions. The research question thus framed proves to be the guideline for the total research. Thus the identification of the AI to be having a greater long term side effect calls for the alternative methods of treatment to be innovated that are not associated with any sort of side effects pertaining to mental or physiological distress.
Chapter 2: Methodology
2.1 Research method
The method includes secondary data and deductive approach. It can be stated that the increasing number of cases related to breast cancer has given rises to several cognitive and screening techniques to treat breast cancers. On the other hand, selection of secondary data is based on the several journals, previous researches and other such related websites. The research Methodology chapter is included in a dissertation in response to provide a systematic and thorough description of the methods utilized for conducting research. However, this chapter plays a vital role in choosing the proper technique and tools for data collection and data analysis. In order to do this, using appropriate tools and techniques helps to reach the aims and objectives of the research and that also helps to meet the research requirements of the study and that is essential for the success of the research. The techniques are being used with the help of ideas based on previous researches. On the other hand, this is a secondary data-based research method and different kinds of topic related systematic review collected to determine the importance of AIs on the treatment of breast cancer patients. On the other hand, it is based on a critical omission of a study that includes fundamental norms and issues related to the breast cancer (Ico-d.org, 2020).
The selection of appropriate research methods is the most important to reach the research aims and objectives as well as this is also important to the accumulation of the information to meet the objectives of the research. In the concerned study, secondary research method qualitative data has been accumulated from the secondary database to fulfil the research aims and meet the research objectives (Kamstraet al. 2017). However, a qualitative research method allows researchers to analyze huge amounts of data that is already published in the secondary database. In order to this systematic review from different sources are collected to determine the importance of AIs on the treatment of breast cancer patients. Moreover, with the help of secondary data analysis the researcher can understand the features and aspects of the AIs on the treatment of this harmful disease. Apart from that, the systematic review provides effective information regarding the current and future use of AIs as well as this also provides effective data related to cognitivedysfunction and this is important to meet the research aims and objectives (Ayedet al. 2019).
2.2 Data collection
Data collection is the most important part of any kind of research and the collection of relevant information is important to meet the aims and objectives of the study and ensure the accuracy of the study. As per the view of Greenlee et al. (2017), it can be stated that information can be collected from different sources such as primary and secondary sources. In the concerned study, the researcher can focus on accumulating data from the secondary sources and most relevant information related to the importance of AIs on the treatment of breast cancer patients can be used to reach the research aims and objectives. It can be stated that for breast cancer there are several therapies and techniques that are being used in breast cancer treatment. The possible methods are surgery or adjuvant method. However, the exercises and screening is also another method that can reduce the chances of extensive breast cancers. The AI treatment is however associated with high incidence of Ai-induced musculoskeletal symptoms. In order to do this most of the secondary information can be collected from published journals, articles and books. In order to this most of the published systematic review collected with the help of PubMed and ProQuest. Moreover, few articles are collected from the university library. In order to this, Total amounts of systematic review collected to determine the importance of the AIs on the treatment of breast cancer patients (Mohajan, 2018).
2.3 Data analysis
Data analysis is the most important patriot of the research and the result of the research depends on the proper data analysis process. The current research is based on the secondary data based on the qualitative data based secondary research method. In order for this thematic analysis, the method is chosen for the analysis of the data with appropriate manners (Hughes et al. 2020). Thematic analysis helps to provide effective information related to the AIs and their importance on the treatment of cancer patients. Approximately 2,088,849 people suffer from breast cancer every year worldwide of 12.3% (wcrf.org, 2018). It has been noted that approximately 1915 women were treated with Letrozole and 959 women were treated with placebo therapy (bcaction.org, 2021). However, the Letrozole therapy can lead to the recurrence of the disease after discontinuation of the treatment. It has been noted that the global cancer incident in women are 25.4% worldwide and this percentage shows a huge rise of breast cancer (wcrf.org, 2018). Moreover, the thematic analysis also helps to understand the current treatment strategy of breast cancer as well as it also helps to understand the importance and use of AIs in the treatment of breast cancer patients (Snyder, 2019). On the other hand, the thematic analysis also provides effective data which is important for the development of the future treatment of breast cancer patients. In this way, thematic analysis helps to meet the research aims and objectives.
2.4 PRISMA diagram
Figure: 2.4 PRISMA diagram
(Source: As influenced by Tam et al. 2017)
2.5 Boolean search table
Keyword
Operator
Keyword
Operator
Keyword
aromatase inhibitor
AND
Breast cancer
AND
Common treatment
Breast cancer
AND
Cognitive dysfunction
AND
Safe and effective therapy
Breast cancer
AND
Aromatase inhibitor
AND
Chemotherapy
Estrogen
AND
Hormone
AND
Cognitive instability
Breast cancer treatment
AND
Mental problem
AND
Physical problem
Table 2.6 Boolean table
(Source: As influenced by Dadheechet al. 2018)
2.6 Exclusion and inclusion criteria
Inclusion
Exclusion
1. Sources from 2015 and above
1. Source and publication before 2015 can be excluded
2. English language only selected for this research
2. Research papers with any other language except English cannot be used here
3. Secondary data-based qualitative research method used for this research
3. Primary research method can be the exclusion criteria of this research
4. Study presented with systematic reviews are considered here
4. Study presented without systematic reviews are excluded from these criteria
Table 2.7: Exclusion and inclusion criteria
(Sources: As influenced by Nayak and Singh, 2021)
2.7 Ethical consideration of systematic review
Ethical consideration is the most important problem in any kind of research undertaking systematic review. However, research in breast cancer is the most important ethical issue and due to this issue, research is also facing several problems. On the other hand, the side effects of the AIs have negative impacts on breast cancer patients and this problem is a major ethical issue of this research. Moreover, the collection of the secondary data can reach the research aims and objectives with appropriate manners and all these acts as ethical considerations of this research (Hawkins et al. 2020).
However, this chapter has taken under consideration various analytical tools as well as methods that have enabled the researcher to properly analyses the topic of research. On the other hand, the researcher used systematic review and thematic analysis and that helps to reach the research aims and objectives. On the other hand, this chapter also focused on the different kinds of ethical obligations, which have negative impacts on breast cancer research. Moreover, this chapter also provides a period and that helps to understand the time-to-time planning of the research and that also helps to the time management of the research on the importance of the AIs on the treatment of breast cancer patients.
Chapter 3: Results
3.1 EE complex formation is important for the functioning of aromatase inhibitor
Figure 2.1: Mode of action
(Source: As influenced by Altundag and Ibrahim, 2006, p.553-562)
It can be stated that approximately 2,088,849 person suffers from breast cancer every year worldwide. This shows a percentage of 12.3% (wcrf.org, 2018). It can be stated that the breast cancer is increasing day by day. On the other hand approximately 1915 women were treated with Letrozole and 959 women were treated with placebo therapy (bcaction.org, 2021). The Letrozole therapy did showed recurrence when the treatment was discontinued though. It has been noted that the global cancer incident is women are 25.4% worldwide (wcrf.org, 2018). AIs are generally employed to control the “breast cancer” in “postmenopausal women”. In this case, AIs is responsible for incomplete oestrogen suppression, and this is also involved in increasing gonadal stimulation. After the suppression of the aromatase, the androstenedione forms oestrone estradiol. Therefore, in the presence of antiestrogen, Oestrone Estradiol (EE) complex forms two major complexes, which are most important to control this disorder (Avvaru et al., 2018, p.609-621). Firstly, EE complex is responsible for the ER activation, and this is the most important for the proliferation of mutated cells, and this plays an important role in the first stage of cancer. On the other hand, the EE complex is also involved in the formation of E2 3,4 Quinone, which is responsible for DNA alkylation, and this is useful to the treatment of the first-stage of “breast cancer” as well as this is also important to the treatment of other types of cancer. It acn b e staed that
3.2 Aromatase inhibitor works effectively at the early stages of cancer development with additional side effects and symptoms
Aromatase inhibitors (AIs) are a type of modern therapeutic agents and this play crucial role on the prevention of first-stage of this type of cancer as well as this kind of therapeutic treatment is also important for the treatment of other complex types of cancer. As per the view of Blaes et al. (2017, p.205-207), AIs are responsible for blocking the activity and expression of the aromatase enzyme, and that inhibits the formation of the Oestrogen, and this is the cause of cognitive dysfunction. There are three major types of inhibitors: Arimidex, Aromasin and Femara are generally used as a therapeutic agent to controlling the early stages of “breast cancer”. However, according to the view, AIs are not involved in blocking the function of ovaries, and that does not suppress the activity of ovaries. This is mainly used for the treatment of postmenopausal women. However, aromatase inhibitors play a wide range of activities. Tamoxifen is generally used for the treatment of these types of patients. Bromley et al. (2019, p.13) depicted that AIs are important for the treatment of early-stage of this disease as compared to tamoxifen. On the other hand, AIs are most important to control the hormone receptor in the case of positive this disease in women. Thus, most doctors prefer this treatment in the first-stage of this disorder as well as this is also important to the treatment of other major types of cancer. On the other hand, the side effects of AIs are very less compared to tamoxifen. Besides these positive impacts, there are different kinds of negative impacts that lead to the negative implication of this treatment. According to the view of Foglietta et al. (2017, p.11-17) opined that continuous use of AIs is the most important cause of blood clots, endometrial cancer and stroke. On the other hand, AIs are responsible for bone loss, and different types of heart problems and sometimes heart failure occurs due to the long-time use of AIs. Moreover, the most important side effect of this treatment is joint pain and joint stiffness. Besides these side effects, they play a crucial role in the treatment of “breast cancer” in most postmenopausal women, and nowadays, this treatment is widely used for the prevention of breast cancer as well as other major types of cancer.
3.3 Estrogen biosynthesis is the main area of effect for Aromatase inhibitors
Aromatase is the most common enzyme, and this is essential for developing this type of cancer. Glück et al. (2013), opined that they are developing this type of cancer in postmenopausal by converting androgen to Oestrogen. However, the formation of Oestrogen is the cause of developing this type of cancer in postmenopausal women. According to the view of Gobbi et al. (2014), more than 60% to 70% post postmenopausal women have oestrogen-dependent carcinomas, and this is the major cause of this cancer. In order to do this, most doctors prefer to use AIs to controlling first-stage “breast cancer”. The aromatase inhibitors are the common enzyme that inhibits the function of the “aromatase enzyme” and this is responsible for the biosynthesis of Oestrogen from androgens.
Figure 3.3: “Oestrogen” biosynthesis
(Source: As influenced by Wakes and Winer, 2019, p.288-300)
The oestrogen biosynthesis occurs by involving the conversation of different kinds of substrate, and this is mainly including a conversation of cholesterol to progesterone and androgen. After that, the androgen formed Estrogen with the help of the aromatase enzyme. Thus, deactivation of the activity is the most important to the prevention ofthese types of disease. According to the suggestion of Goldvaser et al. (2018), oestrogen deactivation can occur in several ways, but the most common mechanism is the use of aromatase inhibitors is the most effective mechanism for the deactivation of oestrogen biosynthesis. In order to this, AIs are directly linked to the aromatase enzyme, and that helps to the formation of the EE complex. After the formation of the EE complex, this complex generates E2 3, 4Quinone, which is responsible for the DNA alkylation and helps repair the abnormal DNA. On the other hand, this EE complex is involved in the activation of the ER enzyme. The ER enzyme is responsible for the proliferation of the mutated cell. Thus, the expression of the AIs in the host cell is responsible for the cognitive implication as well as cognitive dysfunction. In which oestrogen biosynthesis is deactivated, which is most important for the first stage treatment this disease in “postmenopausal women”. Goss et al. (2013) stated that the primary source of the Oestrogen is the breast bone, as well as this is also found in the “central nervous system”, and this hormone helps to the development and growth of the breast cell and bone in females. Thus, the deactivation of oestrogen biosynthesis helps to stop cell proliferation in the breast. Thus, this strategy is a major strategy for the treatment of first stage of this cancer.
3.4 Aromatase inhibitors are effective in treating cognitive dysfunction
Cognitive dysfunction is also known as cognitive impairment, and this kind of disorder can be present at birth and can be achieved in many other ways. On the other hand, this can occur during foetal development, after the short period of birth and the use of different kinds of hormone therapy such as AIs hormone therapy is the most important cause of this disorder. Besides this, there are different kinds of chromosomal abnormalities, such as downs syndrome is the most important cause of cognitive dysfunction. On the other hand, phenylketonuria, hurler syndrome and many other genetic diseases are the most important cause of this disorder. On the other hand, different kinds of complications during the pregnancy period and delivery period may be the cause of cognitive dysfunction. According to the view of Pistelli et al. (2018), using alcohol, drugs, and certain vitamin deficiency are responsible for this disorder. However, using different kinds of “hormone therapy” is the main cause of cognitive dysfunction. In order to this, AIs is a common “hormone therapy” used to the control this type of cancer. As per the view of Robertset al. (2020), this kind of dysfunction is a vital step towards the treatment of breast cancer. This is because this kind of dysfunction is responsible for lowering oestrogen levels in the body by inhibiting the function of the Oestrogen. According to this, most doctors use this strategy to decrease the oestrogen level in the breast cell. The breast cell, bone and central nervous system are the source of “Oestrogen” and this hormone is responsible for the development of these cells (Vodermaier, 2009). However, high levels of Oestrogen are the cause of abnormal cell proliferation and abnormal cell growth, which leads to the development of breast cancer in postmenopausal women. In this case, AIs play an important role in controlling the abnormal biosynthesis of Oestrogen, and that helps to control the abnormal cell proliferation in the breast cell. On the other hand, the use of AIs is the leading cause of cognitive dysfunction and that inhibitors decrease the biosynthesis of Oestrogen by inhibiting the function of aromatase (Tenti et al. 2020). Thus, this kind of cognitive dysfunction, with the help of AIs, is most important and widely used for the treatment of breast cancer. However, the side effects of this treatment have major negative impacts, and most breast cancer patients are facing several problems due to cognitive dysfunction. Most women with breast cancer face abdominal pain, joint pain, fatigue, muscle weakness and many more. On the other hand, suppression of the activity of aromatase enzyme is the cause of lower levels of Oestrogen, and this leads to less development of the breast cell, and a major problem is a functional error in the central nervous system. On the other hand, few women are facing severe problems during their pregnancy period as well as they are facing poor feeding problems and many more. According to the view of (Van Asten et al. 2014),besides the side effect of cognitive dysfunction by the help of aromatase inhibitors is the most useful and effective for prevention of early-stage of this cancer as well as this kind of treatment also used for the treatment of other major types of cancer. It has been noted that Canadian Cancer Trials Group has been funded by Novartis and they have manufacture Letrozole. As per the views of several researches her it has been noted that 1918 were postmenopausal women were assigned Letrozole treatment as a method of preventing cognitive dysfucntioning. On the hand, it has been noticed that 959 women have continued the treatment for 10 years and other who have discontinued the treatment faced recurrence of the cancer (bcaction.org, 2021).
Chapter 4: Discussion and conclusion
4.1 Discussion
In the study the statistics of the women suffering from breast cancer worldwide has been mentioned. It can thus be stated that Aromatase therapy is more effective than other such Letrozole and placebo therapy. On the other hand, the aromatase therapy is also quite easy to handle as well as it can be less painful in comparison to other treatment. However, there are techniques such as screening and chemo that can reduce the growth of cancerous cells in the body. Yet, this are very much avoided because of its excess rates and huge pains. Thus from the thematic analysis it can be seen that Aromatase inhibitors (AIs) are one kind of hormone therapy, and this is generally used to controlling metastatic and normal types of cancer. However, this type of therapy generally used to treat positive hormone receptors to deactivate the biosynthesis of aromatase dependent oestrogen. In the case of this type of cancer, oestrogen level controlling is the most important for the treatment. In addition to this, AIs helps to deactivate the biosynthesis of Oestrogen and power oestrogen level by blocking aromatase. As per the view of Irelli et al. (2020), There are three different kinds of aromatase enzymes used to control this disease and all these are most important for the treatment of the other major types of cancer. The first one is anastrozole which has Arimidex activity, and this is generally used for the deactivation of the aromatase enzyme. On the other hand, the second one is exemestane, and this aromatase inhibitor has Aromasin activity and this enzyme also used in the “breast cancer therapy”, and this AI helps to decrease the oestrogen level in the body. According to the suggestion of Irwin et al. (2015, p.1104-1111), the last one is Letrozole, this inhibitor also known as Femara. This enzyme decreases the oestrogen level in the body, and this is most important to control the first-stage of this cancer. Nowadays, this is an effective treatment of this disease. But in the case of men “breast cancer”, this is not effective, and this is mainly used to treating this type of cancer patients. Moreover, menopausal status is the most important factor for aromatase inhibitors therapy. In order to this, this therapy is most effective for the treatment of postmenopausal women, but this is not effective for normal women. Thus, this treatment is generally used for the treatment of postmenopausal women. However, an aromatase inhibitor is one kind of pill, and this is generally preferred for postmenopausal women. It is a long-term procedure, and the duration of this procedure ranges above five years to 10 years. On the other hand, Kesisis et al. (2009), opined that AIs hormone therapy decreases the risk of cancer in the opposite breast, and this provides disease-free survival of a woman. Moreover, according to the FDA and different kinds of trials, it has been shown that “aromatase inhibitors”, “exemestane” and “anastrozole” can decrease the risk of formation of this type of cancer in female. Thus, this treatment is most effective to control compared to other treatments. Besides this, the side effect is the most important problem of this treatment. The continuous use of this therapy is the cause of joint pain and muscle pain. On the other hand, this is a long-term procedure thus; most women are facing menopausal symptoms. Khosrow-Khavar et al. (2017) suggested that taking this treatment for a long time is the major cause of losing bone density and sometimes, this is the cause of heart attack and stroke. Besides the side effect of this therapy, this is the most important treatment for breast cancer, and this is widely used to prevent breast cancer. It can be stated that the cancer can be treated with several therapies however it is much better to use other recommendations. The less consumption of fast foods, maintaining a regular exercising routine can also helps to treat the cancers along with the aromatase inhibitors.
4.2 Gap in research and future prospects
The gap in the literature is that the previous study described the importance of AIs on the treatment of breast cancer. However, this specific study explored the importance of the use of AIs to control the high risk of “breast cancer in postmenopausal women”. On the other hand, the previous study on this topic has not described the mode of action of the aromatase inhibitor, but this study briefly explains the mode action of an “aromatase inhibitor” to controlling the level of “Oestrogen” in the body and its importance on the treatment of the breast cancer in postmenopausal women. All these gaps in the literature between the present study and past study helps to develop a decision which is most important to an understanding about the research topic on aromatase inhibitor cause of cognitive dysfunction and its importance on the treatment of breast cancer patients.
The main drawbacks of the current study are that it is solely based on literature from previous research which does not validate the results or the conclusion drawn from the results. Further research involving experiments need to be conducted in this regard so as to identify the role of aromatase inhibitor in causing cognitive dysfunction among breast cancer patients. Another major limitation of the research is that articles and papers that are relevant to the research are in many cases paid and thus they could not be accessed owing to the issue of credibility and validity of the research data. This can be resolved by conducting a primary research on this topic in future to counteract the limitations of this research. Further a primary research on this subject will clearly define the varieties of cognitive dysfunction among breast cancer patients which is limited knowledge in case of secondary research. Further research can also be done into the reasons for different cognitive dysfunction among patients and the underlying genetic or history of the patient regarding cause of that dysfunction. This will shed much light on the signal transduction pathway and the molecular pathway responsible for cause of the dysfunction.
4.3 Conclusion
Approximately 2,088,849 people suffer from breast cancer every year worldwide. This shows a percentage of 12.3%. It has been analyses in the study that Letrozole and placebo are not allowing a better treatment as 1915 women are treated with these two drugs and is mentioned in the study. Currently, “breast cancer” is one the most important threats for women. However, Oestrogen is the most important and common hormone that is responsible to the development of “breast cancer” in women. The breast, bone and central nervous system are the most common source of Oestrogen, and this is responsible for the development of breast cells and bone. However, high levels of Oestrogen are the most important cause of cell proliferation. According to the view of Litton et al. (2012), excessive and abnormal cell proliferation is the cause of the development of breast cancer in postmenopausal women. In the early stage of breast cancer, most doctors prefer AIs mediated hormone therapy, and this plays a crucial role in the prevention of this type of cancer in the early stage of cancer development. Aromatase is the most important and essential enzyme for the formation of Oestrogen and that increases the oestrogen level in the body. Thus, high levels of Oestrogen are the cause of cell proliferation and excessive growth of the breast cell, and this is the most important cause of “breast cancer”. In this case, AIs play an important role in lowering the level of Oestrogen in the body, and they reduce cell growth. As well as this is also important to decrease the high risk of breast cancer and other major types of cancer. There are different kinds of AIs used for the treatment of breast cancer, and this is a very long-term treatment procedure. As per the view of Lønning (2011), proper planning such as time to time medication and appropriate therapy is the most important for the success of this kind of treatment. The success of this therapy also depends on the timing, dose and frequency of the treatment. On the other hand, this is a long-term procedure, and doctors have prescribed this therapy for 5 to 10 years. Thus, maintaining time and taking a full dose is most important to get more benefit from this particular hormone therapy. However, the main principle of this treatment is the use of AIs to inhibit the biosynthesis of Oestrogen. The mechanism of these inhibitors are,Generally, they are directly bound to the aromatase enzyme, and then androstenedione testosterone forms a complex which is known as EE complex. As per the view of Lu et al. (2020), this complex acts as an antiestrogen, and they are responsible for ER activation and formation of E2 3, 4Quinone. However, E2 3, 4Quinone is responsible for DNA alkylation, and that helps to repair the abnormal DNA strand present in breast cells. On the other hand, activation of ER helps to control the abnormal growth of the breast cell by controlling the synthesis of Oestrogen. This is the main principle of hormone therapy, and this mechanism is used to control abnormal cell proliferation. In this way, with the help of AIs, doctors can control the abnormal cell proliferation in the breast cell, and this is most important to the treatment of the early stage of breast cancer (Wagner et al. 2020).
As per the above discussion, it can be concluded that this research describes the importance of AIs in the treatment of breast cancer. On the other hand, this research also describes the mode of action of the aromatase inhibitors. As per the above discussion, it can be said that aromatase is the most common enzyme, and this is responsible for the biosynthesis of Oestrogen, and this is generally found in the breast cell. However, high levels of Oestrogen are the cause of abnormal cell development and abnormal cell proliferation, and this leads to breast cancer in postmenopausal women. As per the above discussion, AIs responsible for inhibiting the biosynthesis of Oestrogen thus, this strategy is used to control the “breast cancer in postmenopausal women”.
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