Multicausality: Reserpine, Breast Cancer, and Obesity

Introduction

There is a suspicion that there is an association between reserpine use and the risk of breast cancer development. According to the table of Annual age-adjusted incidence of breast cancer per 100,000 women by body weight and reserpine status, this prediction may match reality. It depicts that people, who apply reserpine on a regular basis, are more likely to have breast cancer in the future. The index for reserpine user is 10.47, while it is 6.14 for other ones. It is evident that there is a connection between reserpine use and the liability to breast cancer development (Abdelfatah & Efferth, 2015). However, it is worthy of taking into consideration that the impact is relatively weak.

Another issue, which causes multiple concerns, regards the built of an individual. There is an assumption that obesity increases the chances of having breast cancer (Argolo et al., 2018). The table, which has already been mentioned above, presents that there is a considerable difference in morbidity statistics. The index of the liability to breast cancer is 8.72 among obese individuals, while it is 4.22 among people with normal built. For this reason, it is possible to conclude that there is obesity may lead to increasing the risk of breast cancer development.

After reviewing the table and the possible risk factors, a logical question follows concerning the possible association between reserpine use and obesity. The table demonstrates that the index for the individuals, who reject reserpine, is 4.10 for normally-built ones and 8.30 for obese participants, while reserpine users have an index of 6.40 and 12.50, respectively. Therefore, it is apparent that the suspicion matches reality, though it is not impactful to a large extent.

In summary, it should be noted that all the aforementioned factors are not significant in the context of the liability to breast cancer development, though their minor influence is undeniable. Whether reserpine use and obesity are combined in a single case, their impact cannot be underestimated (Siddiqui et al., 2020). However, there is no evidence that the association between reserpine and breast cancer is attributable to obesity.

Chronic Obstructive Pulmonary Disease

The focus of the 20-year study is to explore the connections between chronic obstructive pulmonary disease (COPD) and such factors as low SO2 and low FEV1. The participants were copper smelters with high SO2 and truck maintenance workers with low SO2. It should be noted that the majority of them, namely 55% of each group, were smokers. The results revealed that the risk of COPD was significantly higher among smelter with a smoking habit as compared to truck maintenance workers. Therefore, it is apparent that a high SO2 level has an influence on the liability to COPD, as well as smoking on a regular basis.

FEV1 is an important measure for evaluating COPD and monitoring the progression of the disease. The normal result varies from person to person, considering such specialties as age, race, gender, and others. It is helpful in identifying the current stage of COPD (Agusti & Faner, 2018). However, it is not applied for revealing this disease, as another breathing measure named FVC is also required in order to be precise in establishing a diagnosis. The combination of FEV1 and FVC helps to present a comprehensive picture of the lung condition (Agusti & Faner, 2018; Lange et al., 2016). For determining the exact impact of COPD, CAT is also applied. Therefore, FEV1 is the amount of air the patient is capable of forcing in one second, and this measure can be used to diagnose other diseases. For instance, low FEV1 may demonstrate the sign of asthma, and for this reason, it cannot be considered an independent risk factor for COPD. Consequently, it presents the best reason for not controlling for low FEV1 as a potential confounder.

Oral Contraceptive Use, Plasma Homocysteine Level, and Myocardial Infarction

There is a suspicion that oral contraceptive use may lead to myocardial infarction. Roach et al. state that Combined oral contraceptives (COCs) have been associated with an increased risk of arterial thrombosis, i.e. myocardial infarction or ischemic stroke (2015, para. 1). Two possible causal models, which include oral contraceptive use (OC), plasma homocysteine level (HCS), and myocardial infarction (MI), exist. One approach implies the development of MI on the basis of the combination of OC use, HCS factor, other circumstances, which are highly likely to result in the liability to the disease. Therefore, the range of factors leads to MI, and in this case, HCS may be considered to be a confounder of the relationship between OC and MI.

Moreover, there is another sequence of factors, which may end in MI. There is a causal model that implies another connection between OC use and the risk of MI. In this model, HCS may appear to be an interim step, namely applying OC may lead to HCS and then, combined with other risk factors, result in MI. Consequently, analyzing the relationship between OC and MI, in this case, HCS is not a confounder.

Contraception Methods and Their Risks

The Oxford Family Planning Association Contraceptive Study was applied to divide the participants into three groups in accordance with the contraception methods they prefer to use. The study reviews such methods as oral contraception, diaphragm contraception, and intrauterine device (IUD). After reviewing the table, which depicts the results of the research, and the factors mentioned in it, it is possible to note that there are some aspects that may present the sources of bias.

The first one is the factor percentage aged 25-29 years. It becomes evident that there are participants, who refer to other age groups, and the results on them are not covered comprehensively. In addition, participants aged 25-29 are not the majority of using the chosen methods of contraception. This aspect may be the cause of misunderstanding of the study. The second issue, which may lead to bias, is percentage in Social Classes I or II, which may appear not to be informative, considering the topic of the study. The third bias regards the percentage smoking 15 or more cig./day characteristics. This point reveals only the ones, who some actively on a regular basis, though does not pay attention to the individuals, who have the same habit, but preferred to use fewer cigarettes. Other applicants may be considered to be non-smokers, which is highly likely no to match reality.

It is apparent that the study is difficult to be perceived objectively. Moreover, the aforementioned biases may lead to an improper understanding of the relationship between oral contraceptive use and circulatory deaths. Another aspect, which should be highlighted in this context, is the duration of using this method, which appears to have a significant impact on the health state. Apart from this, the factor of age should be broadened and taken into consideration.

References

Abdelfatah, S. A. A., & Efferth, T. (2015). Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells. Phytomedicine, 22(2), 308-318.

Agusti, A., & Faner R.(2018). COPD beyond smoking: New paradigm, novel opportunities. The Lancet, 6(5), 324-326.

Argolo, D. F., Hudis, C. A., & Iyengar, N. M. (2018). The impact of obesity on breast cancer. Curr Oncol Rep, 20(47).

Lange, P., Halpin, D. M., ODonnell, D. E., & MacNee, W. (2016). Diagnosis, assessment, and phenotyping of COPD: Beyond FEV. International journal of chronic obstructive pulmonary disease, 11 Spec Iss, 312.

Roach, R. E., Helmerhorst, F. M., Lijfering, W. M., Stijnen, T., Algra, A., & Dekkers, O. M. (2015). Combined oral contraceptives: The risk of myocardial infarction and ischemic stroke. Cochrane Database of Systematic Reviews, 8.

Siddiqui, M., Bhatt, H., Judd, E. K., Oparil, S., & Calhoun, D. A. (2020). Reserpine substantially lowers blood pressure in patients with refractory hypertension: A proof-of-concept study. American Journal of Hypertension, 33(8), 741747.

Breast Cancer: Research Review Paper

Introduction

Breast cancer is the most common form of cancer among women. However, plenty of scholars investigations help doctors, nurses, and patients to take precautionary and care measures improving their physical and psychological condition.

Gap analysis of the previous investigation

In order to deepen the investigation, the so-called gap analysis was provided as new study would contribute to an understanding of the topic in a way that could improve clinical practice for the nurse practitioner and improve patient outcomes. Previously considered Breastfeeding and the Prevention of Breast Cancer: a Retrospective Review of Clinical Histories article by González-Jiménez, García, Aguilar, Padilla, and Álvarez (2013) suggests the idea that breastfeeding, especially prolonged one reduces the risk of breast cancer, but lactation protects only non-smoking mothers. In its turn, Fostering Early Breast Cancer Detection: Faith Community Nurses Reaching At-risk Populations study by Shackelford, Weyhenmeyer, and Mabus (2014) states that education of faith community nurses of principles of preventive examinations is significant as they would be able to provide a clinical examination and teach women to carry out breast self-examination. Moreover, based on statistic data the article proves that plenty of women living in cities and megacities have higher chances to become breast cancer victims. It happens because of the environmental pollution that negatively affects not only nature but also human himself. That is why African American women and women living in rural areas have low rates of illness and consequently low mortality rates.

Concluding from the reviewed articles one may note that there is a lack of information about overweight and obesity women who suffer from malignant or benign breast tumors. In my opinion, it is of great importance to study the above topic to achieve a complete research.

Obesity as a Key Determinant of the Breast Cancer

Obesity becomes a scourge of the modern humanity. According to statistics, since 1980, the number of obese people has doubled. If earlier it was believed that obesity is a problem only for the countries with high income, now overweight and obese people are found around the world. In 2014, the World Health Organisation released facts that 1.9 billion adults are overweight among which 600 million are obese (Obesity and Overweight, n.d., par. 1). In 2000, for the first time in human history, the number of adults who were overweight was more than the number of adults who were underweight. US rates of obesity of the population are the fourth largest in the world: about 2/3 of the people in America are overweight, including about one-third are obese (Obesity and Overweight, n.d., par. 1). The complications of obesity include dyslipidemia, hypertension, sleep apnoea, and glucose intolerance, claim Dannenberg and Berger (2013, p. 62). Despite the disheartening statistics, the breast cancer death rate is reducing due to early diagnosis and improved treatment methods.

Clinical Relevance of the Proposed Research Question

Speaking of the clinical relevance, it is significant to define the role of a nurse in the process of care of patients with breast cancer. I agree with Denton (2011) who considers that nurse should be familiar with the patients history, previous treatments used and their efficacy, the physical appearance of the lesion, and the patients description of how it liked before (p. 177). A nurse should provide ongoing psychological support including the following aspects: to talk with the patient about the measures to prevent obesity and to dispense physical and emotional stress of the patient in the organization of his rest and rehabilitation.

Moreover, it is important for a nurse to help to overcome the stereotype of public consciousness, according to which all obese people eat in huge amounts all the time. Unfortunately, they usually consume no more food than people of normal weight, and the cause of obesity lies in the presence of complex metabolic disorders leading to the accumulation and deposition of the excess fat. According to Borland (2011, July 20), scientists say that obesity is the biggest avoidable cause of the disease (par. 16). The risk of the breast cancer may depend on genetic predisposition and other factors, but there some things that women can do to reduce the risk of illness. The role of nurses here is to explain and promote the healthy lifestyle, particularly reduction of weight in terms of limiting fast food, alcohol drinking, and other measures. An adequate physical activity that stimulates the process of metabolism of food glucose also contributes to the weight reduction. A treatment of the obesity in order to avoid breast cancer is mainly depending on proper care, adherence, and diet. In this regard, the role of nurses in the effectiveness of the treatment is increasing.

Ideas about Research Design

Every study needs a research design before starting because it is an integral part of the research. Therefore, I need to determine a research method of possible investigation. According to Brown and Simpson (2014), obesity-related postmenopausal tumors are largely dependent on steroid hormones for growth while obese premenopausal women tend to develop triple negative tumors (p. 8). With this in mind, I would like to investigate this group of women. In my research, I would use mixed design of investigation. A qualitative method involves the collection of information in a free form; it focuses on the understanding, explanation, and interpretation of empirical data that is the source of speculation and productive ideas. A quantitative method comprises conducting various surveys based on the use of structured questions of closed type, which corresponds to a large number of respondents. The main objective of quantitative research is to obtain a numerical estimate of the issue or the reaction of respondents towards it. For example, it would be better if the number of obese women was accompanied the explanation of the situation. Accordingly, I would like to provide quantitative research finding out the number of women patients with the breast cancer in different living or social conditions (for example, rural or living in city), of diverse age after menopause and before (40-55), and of different stages of the breast cancer (I, II, III, IV). After that, I would like to interpret and understand the results to make relevant conclusions and contribute to some extent to the breast cancer patients care. Overall, it seems appropriate to interview approximately 250 women from different hospitals, hospices, and, perhaps, at their homes. I consider that the less number of interviewee would lead to the incorrect results.

Conclusion

It should be stressed that the results of the review paper lead to the conclusion that there is a need to conduct an investigation concerning the relation between obesity and overweight and risk of the breast cancer development among women close to the menopause. In my opinion, the research design suggested above is appropriate and deliberated as, precisely speaking, it is women after forty who suffer from the breast cancer more than others do.

References

Borland, S. (2011). Obesity Is Bigger Cause of Breast Cancer than Smoking or Drinking Daily Mail. Web.

Brown, K., & Simpson, E. (2014). Obesity and Breast Cancer: The Role of Dysregulated Estrogen Metabolism. New York: Springer.

Dannenberg, A., & Berger, N. (2013). Obesity, Inflammation and Cancer. New York, NY: Springer.

Denton, S. (2011). Breast Cancer Nursing (2nd ed.). London: Springer-Science.

Obesity and Overweight. (n.d.). World Health Organisation. Web.

Breast Cancer: Analysis and Data Collection

Introduction

This study seeks to answer question relating to a pilot research study done in two health centers in Connecticut to determine the effect of dance and movement on the quality of life for 32 breast cancer survivors. It was undertaken in a period of 12 weeks.

Data Collection Method Used

Data was collected through questionnaires which were self administered to 32 respondents. Data was also obtained from two sample groups; the waiting list and the intervention groups. Statistical and expert techniques were also used to give a deeper insight into the observations (Sandel et al., 2005).

Data Collection Instruments

Data was collected through FACT B questionnaires. The body image scale was a secondary measure. This was used to support the outcomes of the other measures used. Shoulder ROM and the circumference of the arm were measured by an independent individual in the entire response group (Sandel et al., 2005).

Accuracy and reliability of Instruments used

The FACT-B type of questionnaire has been validated in various countries around the world with a primary use in cancer research. A number of countries have incorporated the use of the body image scale in their research studies on cancer victims and its use has been confirmed to be accurate and reliable. However, ROM and circumference of the arm outcomes are not that reliable because they are open to human error. Moreover, reproducibility trials were not done (Sandel et al., 2005).

Statistical or Analytical Methods Used

Variables of a binomial nature were measured using the chi-square tests. In addition, variables of a continuous nature were measured using the t-tests. U tests were used to analyze the data relating to the unevenly distributed time period for the breast cancer treatments. The arm circumference and the ROM were determined by the t-tests. These were used in pairs on the surgery. Linear models of a general nature were used to determine the credibility of the respondents replies. ANOVA measures were used repetitively to determine the effects relating to time as well as effects relating to the X groups. Reviewing of the data was done in an access data base that were incorporated it into an SPSS version (Sandel et al., 2005).

Statistical Values Reported

The FACT B measure improved from 102.0:15.8 to 116.7:16.9 in the intervention group. Compared to the thirteenth week, the waist group recorded statistical figures of 108.1:16.4 to 107.1: 21.3. The statistical figures regarding the impact of the program on the respondents health in the 26th week was significant. This recorded a time effect of P~.03; while the order of training signified P=.25. The shoulder ROM for both intervention and waist list groups also increased. The increase was from about -15oC to 8oC in the thirteenth week. This was quite significant considering the time frame. The body image scale also recorded significant improvement over the period of the program at the 13th and 26th weeks (Sandel et al., 2005).

Conclusion

The study to determine the quality of health was a qualitative research study because it showed a significant improved in the quality of life for the breast cancer victims. All the control measures including body image, FACT B questionnaires and the ROM measures showed an improvement in the quality of life. This therefore means that dance and movement can improve the quality of life for breast cancer survivors.

Reference

Sandel, S., Judge, J., Landry, N., Faria, L., Oullette, R., & Majczack, M. (2005). Dance and Movement Program Improves Quality-of-Life Measures in Breast Cancer Survivors. Philadelphia: Lippincott Williams & Wilkins, Inc.

Breast Cancer: The Story of One Patient

Michelle has always been the funniest person with the most contagious laugh at every family meeting until she was diagnosed with cancer six months ago. I loved visiting my aunt as she would always have a little gift for me  jewelry, which she is obsessed with. Michelle still has the most colorful and extravagant yet elegant outfits at every gathering. With the diagnosis came the change of character, depression, fear in the eyes, and mundane clothes. It is fascinating to trace the gradual transformation of a person throughout a history of the illness, which will be demonstrated by outlining my dialogue with her.

Michelle was diagnosed with breast cancer days prior to her 40th birthday, which she was excited to celebrate. The call from the doctor, as she explains, has divided her life into before and after. The news became devastating for Michelle and her family; thus, she commanded not to express pity in her presence, as she has always wanted to be strong for everyone. Michelle expresses her emotions in the first moments of the news: I was truly betrayed as a woman that the very thing that gives sustenance to a new life could become the death of you. Therefore, that moment became a turning point and the beginning of a long battle with breast cancer.

Breast cancer is a diagnosis each woman is frightened to hear, which becomes a burden for the rest of the life. It is the second most prevalent cancer diagnosed among women in the United States (Mayo Clinic, 2019). In recent years the support and spread of awareness regarding the disease have reached their peak, which consequently helped the disease treatment funding. Such tendency significantly increased survival and decreased death rates specifically related to breast cancer, with the most advanced technology emergence. Even though the diagnosis is highly dangerous, its identification in the early stages, which is the case for Michelle, provides a high probability of fully recovering.

Threatening diagnosis such as cancer is expected to bring a change of character; however, it is always a mystery how a person will take the news and go through an internal battle of fear, devastation, and hope. At the family gatherings, Michelle kept her head high, however internally, she felt obliged to be joyful, when inside I was dying physically and mentally. A depressive and sad mental state is common among patients, and family members are coping with cancer (American Cancer Society, 2020). Mental pressure and fear took over my aunt during the first months of her cancer journey; thus, it is critical to prevent the severe stages of grief.

Michelle has always had the best hair in the family, which every member highly admired at every event. The start of chemotherapy and consequent loss of all the hair significantly worsened the state of my aunts mind. Not only was she frightened each time going through chemotherapy and the indescribable pain it gave, but also the reflection in the mirror afterward, the woman shared. She grieved the loss of her hair, but with that, Michelle felt like she lost her dignity and pride that has always been the fundamental part of self-confidence. All a brave woman saw in herself is a cancer patient instead of a joyful, confident woman, wife, and mother. And in this state, Michelle was diagnosed with depression.

When the overwhelming feelings of death started to take over, Michelle decided it was enough and start directing her mental health into a more positive path. She began therapy and convinced her husband and daughter to do it too so that each of the family members could find a way to deal with the current circumstances. Such treatment is proved to improve the mental health among people with cancer, allowing them to have a better quality of life (American Cancer Society, 2020). Individual and group therapy helped Michelle and her family to look at the situation more positively and channel their fear into expressing love and support.

After talking with each other about their feelings, a woman discovered that her daughter was perhaps even more scared of the illness consequences than Michelle. 13-year old Lilly revealed to her therapist that she was frightened to lose her mother and also feared that breast cancer is what she is going to develop as a woman too. My aunt was shaken with such revelation: I was so focused on myself and my problems that did not even acknowledge how terrified my own daughter was. The incident taught how important it is to listen, support, and encourage one another because it is not just one person that is affected by cancer; it is the whole family, Michelle emphasizes.

When a family member is diagnosed with cancer, it is everyone that is affected by the disease. This is something my aunt did not realize until beginning counseling. The family dynamic significantly changes after the frightening call from the doctor, and from that second, each person is starting to learn the new habits of living. In the first months of my journey, I realized to be focusing more on my grievances, but it is also important to recognize that others are going through the same as you, a woman explains. The tension inside the family radically shifted and disappeared after each of them expressed their feeling and expectations from each other.

Beginning therapy was one of the best decisions my aunt has made during her battle with breast cancer, as it returned her previous positive mindset and united her family more than ever. Talking with the daughter about accurate prognosis, fears and consequences brought them closer as women and as family, ensuring support for each other at all times. Michelle also started to recognize and acknowledge support from her husband, who was trying to be the pillar, when in reality, he was also fearful for his wifes life. Thus, going through individual and group therapy revealed each of the members grievances, teaching one another how to deal with them and show support no matter the consequence.

Luckily, with the loving support of the family and immense internal strength, Michelle is in the final stages of recovering from breast cancer. She is a proud survivor, and although she will never be the same joyful and spirited woman, she has changed into a proud, strong, and loving mother, wife, and daughter that inspires the whole family each day. She has shown integral progress mentally and physically throughout her fight with breast cancer, becoming a better version of herself. After being declared cancer-free, she applied for psychology courses at a local community college. Aunt is now aspiring to become a certified counselor to professionally help women like her battle with destructive thoughts during her cancer journey.

References

American Cancer Society. (2020). Depression. Web.

Mayo Clinic. (2019). Breast cancer  Symptoms and causes. Web.

Understanding Epigenetic Mechanisms in Breast Cancer

Introduction

Human cells become cancerous when they undergo genetic modifications that make them acquire growth and multiplication advantages. Cancerous cells do not carry out normal physiological roles in human beings. The processes that culminate in genetic changes occur in an orderly manner that involves the accumulation of inherited changes that alter the functions of genes. Two classes of genes have been implicated in the development of cancers in human beings (Huang, Nayak, Jankowitz, Davidson & Oesterreich 2011). First, tumour suppressor genes prevent cells from growing and surviving. Second, oncogenes facilitate the processes of cell growth and survival. Research has shown that different mechanisms are involved in converting cells from normal conditions to cancerous states (Grønbæk, Hother & Jones 2007). Grønbæk and colleagues (2007) assert that the mechanisms of cell alterations ultimately modify the proteins that encode nucleotides, alter the number of genes and increase the rate of gene transcription. Signalling pathways in cells are important in maintaining normal cell functions. However, epigenetic and genetic changes have been shown to cause abnormal cell activities by interfering with the normal pathways involved in cell functions. The number of oncogenes could be increased by gaining extra number of chromosomes, amplifying genes, activating point mutations and shifting the building blocks of DNA. Also, tumour suppressor genes could be deactivated by deleting gross regions in chromosomes, deleting small gene portions and deleting specific nucleotides within a DNA sequence.

Epigenetics is the study of how cell activities are inherited through DNA and RNA patterns that are not influenced by nucleotide sequences. Methylation is an example of epigenetic change that has been widely studied. DNA methylation occurs after DNA replication and it is characterised by the addition of methyl groups to DNA molecules at the sites with cytosine residues. Research has shown that cytosine residues are vey close to CpG islands that are marked by a high concentration of guanidine residues (Huang et al 2011). Thus, methylation of DNA occurs in regions with a high concentration of guanidine residues. Bird (2002) asserts that CpG islands are found in about two thirds of gene promoters. Genes with DNA that is hypermethylated are not expressed. On the other hand, hypomethylation is correlated with increased gene activities. Thus, it could be expected that cancer cells have DNA molecules that are hypomethylated. Specifically, oncogenes are hypomethylated while tumour suppressor genes are characterised by high levels of hypermethylation. Thus, it could be asserted that DNA methylation has implications for the development and progression of cancer.

DNA methylation

Research has identified three enzymes that are associated with DNA methylation in human beings. First, DNA methyltransferase 1 (DNMT1) is involved in maintaining methylation patterns in cells. Second, DNA methyltransferase 3A (DNMT3A) is concerned with regulating de novo methylation processes in cells. It has also been suggested that DNA methyltransferase 3B (DNMT3B) has the same functions as that of DNMT3A (Chen et al 2007; Chedin 2010). The three enzymes are expressed at different rates, but their modes of expression do not always correlate with hypomethylation and hypermethylation. The variations are caused by the action of miRNAs that regulate the molecular events of DNMT (Blair and Yan 2012).

There are different mechanisms for DNA methylation. One of the best explained mechanisms is through the involvement of TET1-3 proteins, which belong to hydroxylases (Tahiliani et al 2009). The molecules catalyse the conversion of 5mc, 5HMC, 5fC and 5caC (Ito, DAlessio, Taranova, Hong, Sowers & Zhang 2010; He et al 2011; Pfaffeneder et al 2011).

DNA methylation

Point mutations due to DNA methylation

Grønbæk and colleagues (2007) show that point mutations are promoted in regions characterised by 5mc residues through many ways. A cytosine that could be methylated could encounter deamination to form a thymine. If the changes are not corrected by independent molecular events in cells, then they result in disease due to point mutations in regions coding for genes. In most cases, genes that are affected are those that are concerned with the regulation of cell growth and survival. More than 30% of human diseases that are associated with point mutations have been shown to have alterations at the CpG dinucleotides.

Chromatin and histone modification

Chromatin is the physiological template for the human genome. The basic unit of chromatin is the nucleosome that is characterised by about 200bp of DNA. The base pairs are organised in small basic units of proteins that exist as octamers. A collection of octamers is known as histone. Thus, histone is the major molecular material that is involved in organising and maintaining the structural integrity of DNA and genes. The human DNA has been found to lie on the surface while histone materials are found in the inner parts of histone molecules. Nucleosomes are part of euchromatin and heterochromatin. Also, euchromatin and heterochromatin are found in mitotic chromosomes. However, heterochromatin and euchromatin of the human genome differ significantly in terms of structure and function. Heterochromatin is packed tightly to prevent transcription factors from accessing histone. On the other hand, euchromatin is not tightly packed. Thus, factors involved in transcription could easily access major regions of DNA that are involved in the initiation of transcription of DNA (Richards & Elgin 2002).

Chromatin and histone modification

Research has also shown that cancer could be caused by epigenetic modifications that alter the normal structure of histone. DNA molecules in every cell nucleus wraps around histone materials, which have an extensive altered N-terminal tails that could also be flexible. The rate at which transcription of DNA occurs greatly depends on specific alterations that could either tighten or loosen molecules of DNA from histone (Blair and Yan 2012).

Chromatin and histone modification

Some alterations of histone correlate with active genes such as trimethylation in histone H3. Some changes could also be connected with genes that could be repressed such as H3K9me3. Acetylation of histone occurs when histone acetyltransferases (HATs) catalyse the addition of acetyl groups to lysine residues. The remove of such residue is catalysed by histone deacetylase (HDACs). Methyl groups are removed through the action of histone demethylases (HDMs). Another important modification of histone is phosphorylation, which ensures that essential residues in histone are phosphorylated. The roles of the enzymes that catalyse the activities of phosphorylation, methylation, and acetylation are not clearly understood (Blair & Yan 2012).

Breast cancer

Research shows that BRAC1 and BRAC2 genes could be responsible for coding proteins that make breast cells grow and multiply abnormally. Disease progression and degrees of severity vary among the different types of breast cancer (Stecklein, Jensen & Pal 2012). If a patient lacks the three receptors that signify the presence of breast cancer, then such a patient is said to be triple negative. It has been shown that a patient presenting with cancer characterised by this state (triple negative) could be difficult to treat. In such patients, there are no readily available hormonal therapy approaches that could be used to treat cancer. Patients who present with cancers characterised by estrogen receptor (ER) tumours are treated using hormonal therapy. Clinical data also show that trastuzumab (Herceptin®) has been used to treat patients with human epidermal growth receptor (HER) positive tumours (Blair & Yan 2012). Epidermal growth factor has been correlated with cancers with high rates of metastasis and invasiveness. Such tumours are quite difficult to treat, especially when they are treated at advanced stages. At such advanced stages, the tumours could have spread to other body organs where they cause physiological damage. However, the effect of EGFR on the development and progression of breast cancers has been reduced through the use of tyrosine kinase inhibitors. An example of such inhibitors is gentinib. The pharmacological product has also been shown to target cells with over-expression of HER2.

Many forms of breast cancer are hypomethylated (Soares, Pinto, Cunha, Andre, Barão, Sousa & Cravo 1999). The observation is similar to findings from other studies (Hinshelwood & Clark 2008). Hypermethylation in noncancerous cells does not occur in the same regions like those in cancer cells (Hinshelwood & Clark 2008). This is a major observation that differentiates molecular events between caner and healthy cells. In order for cancer to progress, tumour suppressor genes need to be suppressed. If they are suppressed, then they lose the ability to prevent the growth of tumours associated with the progression of cancer. DNA hypermethylation results in unstable genes that could lead to cancer. In fact, a significant number of unstable genes results in various forms of cancer because they code for abnormal proteins that facilitate cells to grow abnormally.

DNMTs could be involved in gene-based methylation that is common in breast cancer (Girault, Tozlu, Lidereau & Bièche 2003). However, a weak correlation between DNMTs and breast cancer has been demonstrated. Methylation of the promoter of ER could result in the down-regulation of ER. Breast cancers with over-expressed ER and PR are treated through the use of drugs that imitate the receptors (Blair & Yan 2012). Scientists have concentrated on deciphering the roles of HMTs and HDMs in the development and progression of breast cancer. Such efforts have shown that there are elevated levels of H3K27 methyltransferases, which enhance the activities of zeste homologue 2 (EZH2). Cancer states that are characterised by elevated levels of H3K27 methyltransferases have fast rates of metastasis. Such cancers are difficult to treat and manage. Breast cancer is also associated with over-expression of lysine-specific demethylases that are involved in the removal of methyl groups from lysine residues. Research has demonstrated that there is over-expression of H3K4 demethylase in ER negative tumours. In fact, this is being used as a diagnostic marker for breast cancers that have high chances of metastasising.

The discovery of the genes and molecules involved in the development and progression of breast cancers has been very sequential. The orderly manner in which scientists have been discovering breast cancer-specific genes and molecules has greatly impacted the management of the disease. For example, hormonal therapy has been adopted in the treatment of breast cancers that are characterised by ER. In the future, further research could result in the identification of more genes and molecules with regard to breast cancer. Therefore, more treatment approaches would be designed in the future.

Aim and objective

DNMT1 is essential in maintaining DNA methylation pathways. If the enzyme is over-expressed, then hypermethylation occurs. This is the implication for many forms of breast cancer (Girault et al 2003). The proposed study aims at assessing the effect of demethylation on the growth of normal human cells and development and progression of breast cancer cells. The study will use the wound healing method that is often used in the study of the biology involved in the migration of cells (Francisco et al 2003).

Hypothesis

The study hypothesises that a significant change (arrest of cell migration) will be observed when breast cancer cell lines will be demethylated using a demethylating enzyme.

Materials and methods

Assays will be conducted in a biotechnology laboratory that will have all the required facilities.

Cell lines

The MCF-10A and HMT-3522 will be the normal epithelial cells and the T47D and ZR-75-1 will be breast cancer cell lines that will be utilised in the study.

Protocol

A standard protocol will be used to maintain the cell lines in vitro. All cell lines will be allowed to grow in independent dishes for a period of 48 hours. The dishes will be supplied with RPMI-1640 that will contain essential growth materials such as L-glutamate, penicillin, streptomycin and 50% carbon dioxide. A temperature of 370C will be maintained. DNMT1 (methylase) will be added to the normal epithelial cells while 5-methylcytosine (demethylase) will be added to breast cancer cell lines. The cells will then be monitored for a period of 24 hours. Controls will not have either a demethylating or methylating enzyme added. A wound will be stimulated by scratching the cell structures in the plates at an angle of 30 degrees. A sterile needle will be used. After 24 hours, cells will be washed using HBSS. Images will be taken every six hours to observe cell migration patterns. The metric relative wound density method will be utilised to determine the rate of cell migration. Afterwards, an automated Incucyte FLR machine will be used to achieve live cell imaging.

Analysis

The images that will be obtained from the cell migration (wound healing) assay will be studied through the use of MVTec software. In order to obtain a graph, the relative wound density assay figures will be plotted against time take to achieve specific distances of cell movements.

Expenditure of main reagents

Reagent Cost (pounds)
5-methylcytosine demethylase 176.20 for 500mg
FBS 122 for 200mg
HEPES buffer 73.60 for 200ml

Figure 4. Table showing the reagents to be used in the study and their prices.

Health and safety

Health and safety are important when conducting research activities in scientific laboratories. Precautions will be taken so that the various chemicals in the laboratory cannot cause harm to the personnel working in the laboratory. Standard health and safety procedures have been developed to help tom protect personnel in laboratories from any harm. Also, the standard procedures aim at protecting the environment from the negative impact of laboratory chemicals. Health and safety procedures will be used at all times while conducting the proposed study. Laboratory coats and gloves will be used. Contaminated materials will be decontaminated using standard procedures.

References

Bird, A, 2002, DNA methylation patterns and epigenetic memory, Genes & development, vol. 16, no. 1, pp. 6-21.

Blair, LP, & Yan, Q, 2012, Epigenetic mechanisms in commonly occurring cancers, DNA and cell biology, vol. 31, no. 1, pp. 49-61.

Chedin, F, 2010, The DNMT3 family of mammalian de novo DNA methyltransferases, Progress in molecular biology and translational science, vol. 101, no.1, pp. 255-285.

Chen, T, Hevi, S, Gay, F, Tsujimoto, N, He, T, Zhang, B.,& & Li, E, 2007, Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells, Nature genetics, vol. 39, no. 3, pp. 391-396.

Francisco, J. A., Cerveny, C. G., Meyer, D. L., Mixan, B. J., Klussman, K., Chace, D. F.,& & Wahl, A. F. (2003). cAC10-vcMMAE, an anti-CD30monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood, 102(4), 1458-1465.

Girault, I, Tozlu, S, Lidereau, R, & Bièche, I, 2003, Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas, Clinical Cancer Research, vol. 9, no. 12, pp. 4415-4422.

Grønbæk, K, Hother, C, & Jones, PA, 2007, Epigenetic changes in cancer. Apmis, vol. 115, no. 10, pp. 1039-1059.

He, YF, Li, BZ, Li, Z, Liu, P, Wang, Y, Tang, Q,& & Xu, GL, 2011, Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA, Science, vol. 333, 6047, pp. 1303-1307.

Hinshelwood, R. A., & Clark, S. J. (2008). Breast cancer epigenetics: normal human mammary epithelial cells as a model system. Journal of molecular medicine, 86(12), 1315-1328.

Huang, Y, Nayak, S, Jankowitz, R, Davidson, NE, & Oesterreich, S, 2011, Epigenetics in breast cancer: whats new?, Breast Cancer Research, vol. 13, no. 6, pp. 1-11.

Ito, S, DAlessio, AC, Taranova, OV, Hong, K, Sowers, LC, & Zhang, Y, 2010, Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification, Nature, vol. 466, no. 7310, pp. 1129-1133.

Pfaffeneder, T, Hackner, B., Truß, M, Münzel, M, Müller, M, Deiml, CA,& & Carell, T, 2011, The discovery of 5formylcytosine in embryonic stem cell DNA, Angewandte Chemie, vol. 123, no. 31, pp. 7146-7150.

Richards, EJ, & Elgin, SC, 2002, Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects, Cell, vol. 108, no. 4, pp. 489-500.

Soares, J, Pinto, AE., Cunha, CV, Andre, S, Barão, I, Sousa, JM, & Cravo, M, 1999, Global DNA hypomethylation in breast carcinoma, Cancer, vol. 85, no. 1, pp. 112-118.

Stecklein, SR., Jensen, RA, & Pal, A, 2012, Genetic and epigenetic signatures of breast cancer subtypes, Front Biosci (Elite Ed), vol. 4, no. 1, pp. 934-949.

Tahiliani, M, Koh, KP, Shen, Y, Pastor, WA, Bandukwala, H, Brudno, Y,& & Rao, A, 2009, Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1, Science, vol. 324, no. 5929, pp. 930-935.

BRCA Gene Mutation and Breast Cancer

Abstract

Cancer remains one of the major threats to human health. It occurs as a result of gene mutation. Breast cancer is the most prevalent cancer among women. Additionally, breast cancer affects men, though in rare cases. The disease occurs as a result of mutations in breast cancer susceptibility genes 1 and 2. The genes produce proteins that facilitate the restoration of damaged DNA. Mutations in the BRCA 1 and BRCA 2 genes inhibit the recovery of DNA leading to subsequent alterations in the DNA. The changes result in the cells growing and splitting uncontrollably causing cancer. Breast cancers are classified based on the available hormone receptors. Physicians use radiotherapy, operation or chemotherapy to assist individuals suffering from breast cancer. The operation entails the amputation of the infected breast. On the other hand, chemotherapy and radiation therapy kill the cancer cells or prevent them from multiplying.

Introduction

Cancer is the leading killer disease in the world. Easton, Ford and Bishop (2005) maintain that cancer refers to a collection of illnesses that involve irregular cell growth and are likely to attack different parts of the body. According to Easton et al. (2005), it is important to understand that not all cell growths are cancerous. They cite benign tumors as one of the diseases that are not cancerous. Cancer accounts for at least 20% to 46% of the deaths. Currently, cancer is prevalent in developed countries. The risk factors associated with the disease include old age, ethnicity, environmental conditions, diet, and lifestyle. Breast cancer is one of the leading killer diseases among women. Cancer results from a hereditary gene mutation. Easton et al. (2005) cite breast cancer susceptibility genes 1 and 2 (BRCA 1 and BRCA 2) as the common types of gene mutations that lead to breast cancer. BRCA 1 and BRCA 2 mutations can be acquired from either parent and can result in both men and women suffering from cancer. Prevention is the ultimate way of dealing with cancer. Environmental factors contribute to at least 70% of cancer cases. Lifestyle change can go a long way towards combating the disease.

Research Objective

The primary objective of this study is to determine how BRCA 1 and BRCA 2 gene mutations contribute to breast cancer. The study will also analyze the role of BRCA1 and BRCA 2 in the restoration of the damaged DNA as well as the different categories of breast cancer.

Literature Review

Breast Cancer

Breast cancer occurs as a result of irregular duplication of cells in the breast leading to a tumor. Breast cancer is prevalent in women. However, it does not mean that men cannot suffer from breast cancer. Mostly, breast cancer occurs as a result of the irregular reproduction of the cells that surround the milk ducts. Breast cancer is hard to detect during the early stages because it does not cause pain (Fackentha & Olopade, 2007). As the disease progresses, the signs become apparent. The symptoms include nipple discharge, change in the shape of the breast, a lump in the breast, and skin irritation among others. Nonetheless, the symptoms may differ due to numerous conditions. A person may exhibit these symptoms and not be diagnosed with breast cancer. In the United States, at least, 12% of the women suffer from breast cancer. Researchers claim that in 2015, the United States reported over 230,000 new cases of breast cancer. The gene transformations that lead to breast cancer are common among particular communities. Besides, the gene mutations are prevalent in particular geographic zones.

Classification of Breast Cancer

After the biopsy, the breast tissues are analyzed to establish if they have breast cancer. The medical practitioners use progesterone receptors (PR) and estrogen receptors (ER) to classify breast cancer. Gayther et al. (2011) hold that receptors refer to proteins found in the cells. The proteins get fastened on particular substances like hormones that distribute the blood. The ordinary breast cells and some cancer cells constitute receptors that embed to progesterone and estrogen. The progesterone and estrogen often hasten the development of breast cancer cells. A critical step in assessing breast cancer entails examining the tumor extracted from surgery or biopsy to determine if it contains progesterone or estrogen receptors. The breast cancers that constitute estrogen receptors are known as ER-positive (ER+) cancers. On the other hand, those that have progesterone receptors are referred to as PR-positive (PR+) cancers. The doctors must test the presence of these hormone receptors in all kinds of breast cancers. According to Gayther et al. (2011), over 67% of the breast cancers contain one of the receptors.

Breast cancers are categorized according to the hormone receptor present. Additionally, the doctors consider if cancer comprises too much of human epidermal growth factor receptor 2 (HER2). The breast cancers that do not constitute the hormone receptors are referred to as hormone receptor-negative. At times, the doctors use the term hormone-negative to apply to these types of cancer (Gayther et al., 2011). Such tumors are hard to cure using hormone therapy drugs. The hormone-negative tumors grow rapidly and affect women who have not reached the menopause stage. Some breast cancers constitute either progesterone or estrogen. Such tumors are referred to as hormone receptor-positive. The diseases can be cured using hormone therapy drugs. The drugs minimize estrogen intensity or obstruct estrogen receptors. Hormone receptor-positive cancers develop slowly. However, they may recur after an extended period.

Studies on the models of gene expression have resulted in novel ways of grouping breast cancer. Today, doctors classify breast cancer based on the appearance of tumors when observed using a microscope. Doctors have come up with four groups of breast cancers depending on the molecular characteristics of the tumor. The mode of examining breast cancer based on the molecular structure of the tumor is referred to as Prosigna Breast Prognostic Gene Signature Assay (PAM50). The method is useful in testing HER2 and hormone receptors. The four groups of cancer are luminal A, luminal B, HER 2 type and basal type. According to Gayther et al. (2011), luminal A and luminal B types of breast cancer are ER+. Godlewski and Kapu[ciDska (1996) allege that the structure of the gene expression in the tumors is akin to standard cells that cover the milk ducts. The luminal A tumors do not develop rapidly and are easy to diagnose. Conversely, the luminal B cancers develop rapidly. The tumors have a hideous appearance (Godlewski & Kapu[ciDska, 1996). The HER2 types constitute additional copies of the human epidermal growth factor receptor 2. These types of breast cancer have a nice facade when observed through a microscope. The cancers grow fast and can be healed through targeted therapies. The basal types of breast cancers do not have both the progesterone and the estrogen receptors. Further, the cancers have a standard amount of human epidermal growth factor receptor 2. The basal type of breast cancer mostly affects women with BRCA 1 gene mutations.

The Function of BRCA Genes

The breast cancer susceptibility genes fix proteins that facilitate in genome protection. According to King, Marks and Mandell (2003), BRCA 1 protein and BRCA 2 protein are two types of protein that work in diverse phases of the DNA restoration course. King et al. (2003) argue that the breast cancer susceptibility gene 1 protein is a DNA damage reaction protein. The protein plays key roles on both checkpoint activation and DNA restoration. On the other hand, BRCA 2 protein facilitates the conciliation of the crucial processes of homologous recombination. The scientists are yet to understand the relationship between the two proteins. However, researchers claim that the two proteins have to be available to elucidate the striking association of human cancer vulnerability that results from germline mutations in BRCA 1 and BRCA 2. Apart from DNA restoration, BRCA genes help in transcription management in reaction to DNA damage. Latest studies hold that BRCA1 and BRCA 2 proteins are vital in the preservation of chromosomal equilibrium, therefore ensuring that the genome remains unaffected. Research shows that BRCA 1 and BRCA 2 proteins transcriptionally control several genes that facilitate apoptosis and the cell cycle (Yoshida & Miki, 2004). A majority of these functions are made possible through the interaction between BRCAs and numerous cellular proteins. Rennert et al. (2007) claim that BRCA proteins also facilitate several phosphorylation processes. Nonetheless, scientists are yet to understand how phosphorylation-triggered molecular conduits help to prevent tumor.

Genes Associated with Breast Cancer

Rennert et al. (2007) argue that cancer arises as a result of accumulation of mutations in vital genes, which lead to cells developing and splitting uncontrollably forming a growth. In the case of breast cancer, the genetic transformations arise in the course of an individuals life and are found in specific cells in the breast. The affected genes are those that manage cell development and division. The mutation may also arise in the genes that restore damaged DNA. The genetic transformations are referred to as somatic mutations and are not hereditary. Breast cancer occurs mainly due to somatic mutation of different genes. The common gene mutations that occur in other body cells do not significantly contribute to the development of breast cancer. The genetic transformations that occur in most cells of the body are known as germline mutations. The mutations are hereditary. Most breast cancers that affect members of the same family are as a result of genetic mutations in some genes like BRCA 1 or BRCA 2. The BRCA 1 and BRCA 2 are regarded as high penetrance since they are disposed to causing ovarian cancer, breast cancer and many other varieties of cancer particularly in women with mutations (Roy, Chun & Powell, 2012). Besides, men with mutations in BRCA 1 and BRCA 2 genes are also likely to suffer from breast cancer and other types of cancer.

The BRCA 1 and BRCA 2 manufacture proteins that facilitate the repair of spoilt DNA. On the other hand, the DNA guarantees the constancy of genetic information of the cells. The proteins help to stem tumor by preventing cells from developing and splitting uncontrollably. Mutations in BRCA 1 and BRCA 2 inhibit the restoration of DNA, thus enabling devastating mutations to occur in DNA. Increased mutations in the DNA result in the cells growing and splitting uncontrollably to form a growth (Roy et al., 2012). Breast cancer can come as a result of other numerous exceptional genetic syndromes. They include Cowden syndrome that happens due to mutations in the phosphatase and tensin homolog (PTEN) genes and a Li-Fraumeni syndrome that occurs as a result of mutations in the tumor protein p53 (TP53) genes.

Treatment of Breast Cancer

A person suffering from breast cancer may opt for radiotherapy. Radiotherapy entails the use of radiations to kill cancerous cells. The radiations help to prevent cancer cells from multiplying. The doctors may also treat cancer using drugs (chemotherapy). Chemotherapy involves the use of drugs to cure cancer (Yoshida & Miki, 2004). The drugs help to kill cancer cells or prevent them from multiplying. Chemotherapy is mostly administered through the mouth. However, it can also be introduced into a muscle or vein through injection. The administration of chemotherapy depends on the phase and type of breast cancer. Today, doctors also use hormone therapy to treat breast cancer. The treatment entails the deletion or obstruction of hormones that contributes to the growing of cancer cells. For instance, the doctors conduct ovarian ablation to terminate the production of estrogen, which promotes the growth of breast cancer.

Research Methodology

The study will rely on qualitative data. The researcher will gather data from peer-reviewed journals and other appropriate publications. The researcher will rely on online libraries like EBSCOhost, JSTOR, and PubMed among others.

Sampling Technique

The study will use any journal that touches on BRCA 1 and BRCA 2 and their correlation to breast cancer. The researcher will not use probability sampling because the study does not intend to come up with statistically representative samples. Besides, the researcher does not intend to make any statistical inferences from the study. The pollster will use purposive sampling to select the necessary journals.

Data Processing and Analysis Procedures

The researcher will use phenomenological method to process the data obtained from diverse journals. The researcher will go through the collected data to understand it. After understanding the data, the researcher will generate units of meaning. The pollster will be careful not to make redundant subjective judgments. The diverse units of meaning will then be merged to develop the units of significance. Later the researcher will summarize the data collected from the different journals ensuring that they capture the essential information. The pollster will then identify the themes that are common in a majority of the journals and use them to compile the findings of the study.

Conclusion

Cancer is the leading killer disease in the contemporary world. Breast cancer is the most prevalent form of cancer among women. However, breast cancer also affects men, though in rare cases. Breast cancer occurs as a result of BRCA 1 and BRCA 2 genes mutations. The cancer is classified according to the hormone receptors present. Hormone receptor-negative cancers are breast cancers that do not contain hormones. The tumors that constitute estrogen receptors are called estrogen receptor-positive cancers. Those that contain progesterone receptors are known as progesterone receptor-positive cancers. Other types of tumors include luminal A, luminal B, and HER2 types of cancer. The primary function of BRCA1 and BRCA 2 is to facilitate the restoration of damaged DNA. Breast cancer affects the genes that promote the repair of DNA. Numerous exceptional genetic syndromes can also lead to breast cancer. They include Cowden and Li-Fraumeni syndromes. Breast cancer can be cured by surgery, radiation therapy or chemotherapy. The operation entails the amputation of the infected breast. On the other hand, radiation therapy and chemotherapy target the cancer cells. The therapies either kill the cancer cells or prevent them from multiplying.

References

Easton, D., Ford, D., & Bishop, D. (2005). Breast and ovarian cancer incidence in BRCA 1-mutation carriers: Breast cancer linkage consortium. American Journal of Human Genetics, 56(1), 265-271.

Fackentha, J., & Olopade, O. (2007). Breast cancer risk associated with BRCA 1 and BRCA 2 in diverse populations. Nature Reviews Cancer, 7(3), 937-948.

Gayther, S., Mangion, J., Russell, P., Seal, S., Barfoot, R., Ponder, B., Stratton, M., & Easton, D. (2011). Variations of risks of breast and ovarian cancer associated with different germline mutations of the BRCA 2 gene. Nature Genetics, 15(2), 103-115.

Godlewski, D., & Kapu[ciDska, M. (1996). BRCA1 and BRCA2 genes: New risk factors in hereditary forms of breast cancer and ovarian carcinoma. Reports of Practical Oncology, 1(1), 53-55.

King, M., Marks, J., & Mandell, J. (2003). Breast and ovarian cancer risks due to inherited mutations in BRCA 1 and BRCA 2. Science, 302(5645), 643-671.

Rennert, G., Bisland-Naggan, S., Barnett-Griness, O., Bar-Joseph, N., Zhang, S., Rennert, H., & Narod, S. (2007). Clinical outcomes of breast cancer in carriers of BRCA 1 and BRCA 2 mutations. The New England Journal of Medicine, 357(2), 115-123.

Roy, R., Chun, J., & Powell, S. (2012). BRCA 1 and BRCA 2: Different roles in a common pathway of genome protection. Nature Reviews Cancer, 12(1), 68-78.

Thompson, D., & Easton, D. (2005). Cancer incidence in BRCA 1 mutation carriers. Journal of the National Cancer Institute, 94(18), 1358-1365.

Xu, J., Wang, B., Zhang, Y., Li, R., Wang, Y., & Zhang, S. (2012). Clinical implications of BRCA gene mutation in breast cancer. Molecular Biology Reports, 39(3), 3097-3102.

Yoshida, K., & Miki, Y. (2004). Role of BRCA 1 and BRCA 2 as regulators of DNA repair, transcription and cell cycle in response to DNA damage. Cancer Science, 95(11), 866-871.

Breastfeeding As A Prevention Of Breast Cancer

Introduction

An enormous increase in the incidence of breast cancer among women is widely seen. Prevention is always the better option, than fighting the disease. Mostly women do initiate the practice of breast feeding soon after giving birth, but majority does not put much effort to continue it .The exact relationship between duration of breast feeding and breast malignancy is not understood or rather, neglected by the public. Hence forth it is pivotal to know how longer or shorter feeding practices increase or decrease the risk of breast malignancy. So, as a registered nurse, author can gain a better knowledge if ,the length of breast feeding can bar off neoplasm of breast.

Analysis

According to an article published on a study, (Breast cancer and breast feeding: 2002), data was collected individually from 47 studies,which was epidemiological studies and involving 30 countries.The data included patterns of breast feeding .This was done among women diagnosed with breast neoplasm accounting for 50302 and women without the disease as control groups accounting for 96973.A collaborative reanalysis of the data collected was performed.The findings were quiet interesting since it paved the way to a link between duration of breast feeding and possible chances of getting a breast cancer. Only a few women with beast cancer provided breast feeding when compared to the control group.(71% and 79%) respectively and that too for a very short duration,9.8 months which is far less than control groups with 15.6 months.For every 1 year of feeding, there was 4.3% lesser risk of developing malignancy.The study ,without doubt, concluded that the more prolonged the duration of breast feed is , the lesser is the risk of getting malignancy of breast.

Another study published( Kim Y,Choi JY,Lee KM et al( 2007) , was carried out in a hospital setting in Korea.It was a case – controlled analysis where the candidates were Korean women who had a positive histology findings for cancer of breast.They were a total of 753 in number and controls were also in the same number.The assessment of risk was carried out by unconditional logistic regression models.The inference from the study was that, The risk of cancer of breast was directly proportional to the months of breast feeding.For a women who breast fed for one year , there was an alarming, 56% lesser risk of breast malignancy than a women who fed for 1 to 4 months.

Conclusion

After thoroughly analyzing the studies and evidences, it can be concluded that there is a strong relationship between the occurrence of breast cancer and length of breast feeding. The longer a women breast feed, the slightest is the chance of getting a breast malignancy. The findings are appropriate and applicable for women in countries like Australia, where the breast feeding time period is considerably short among the new mothers and cases of cancer of breast are intensifying day by day. Various awareness programs and campaigns on promoting breast feeding for a longer duration and its preventive effect on breast malignancy, from both the side of health care professionals and government is highly recommended as an eye opener for all the women.

Breast Cancer In Australia: Risk Factors And Treatment

What is Cancer?

Cancer is an abnormal growth of cells in the human body that tend to grow uncontrollably and metastasise (spread to other parts of the body via metastasis, the process of growth of a secondary malignant kind away from the primary site of cancer) rapidly (in most cases). These cancers can involve any piece of tissue in the human body and are generally named as such (William C. Shiel Jr., 2018).

Many people mistake tumours for a type of cancer, however, in many cases, tumours are not cancerous at all however they run the risk of becoming cancerous if untreated. A tumour is defined a swelling in the human body, generally without inflammation, caused by an abnormal growth of tissue, whether benign or malignant (Lexico (Oxford), date unknown). Benign meaning a disease (in this case a tumour) that is not harmful in effect (Lexico (Oxford), date unknown). Malignant, which is the opposite of benign, thus tends to invade normal tissue and can recur after removal or be cancerous (Lexico (Oxford), date unknown).

The main differences are that cancer is a disease in which cells, almost anywhere in the body, begin to divide uncontrollably and a tumour is when this uncontrolled growth occurs in solid tissue such as an organ, muscle, or bone and leads to swelling, they may not also be harmful to the body if removed. A cancer can also be in liquid form and spread via the blood, a tumour can only be in solid form.

Cancers and tumours are incredibly harmful to the body as they do not die at the natural end point of the cellular life cycle, instead they continue to grow and reproduce rapidly, this rapid growth then leads the body to use energy (adenosine triphosphate/ATP) as well as other valuable nutrients that a regular (necessary) cell needs to grow and to function correctly, instead of using it on the other, more necessary cells, this can lead to many outcomes such as organ failure, immune system vulnerabilities and even death. Cancers and tumours, because they grow quickly and die a lot slower inhibit many of the body’s natural processes. Please see below of the hypothetical series of mutations leading to cancer.

Breast Cancer

Location in the body

Breast cancer most often begins to occur in the milk production ducts of the breasts, it may also occur in the lobules of the breasts (glandular tissues). These common forms of Breast cancer are called Invasive Ductal Carcinoma and Invasive Lobular Carcinoma, respectively. Breast cancer, however, can occur in any part of the breast as cancer can occur in any part of the human body. A person diagnosed with early stage breast cancer has a 99% chance of survival for at least 5 years.

Number of cases annually

In Australia in 2018 approximately 18,087 women were diagnosed with invasive breast cancer, with approximately 49 women being diagnosed with it each day.

Risk factors:

The main risk factors of Breast Cancer include:

  • Being a female, men can get breast cancer, but this only occurs about 1% of the time.
  • If you have a strong family history of getting breast cancer you are more likely to get it.
  • Previous Diagnosis of Breast Cancer.
  • Inheriting a faulty gene from your mother or father you are also much more susceptible.
  • Exposure to chest radiation during childhood.

Less common Risk Factors that slightly increase the risk include:

  • Starting menstruation before 12 years of age.
  • Starting menopause after the age of 55 years.
  • Not breastfeeding – The longer you breastfeed, the more you lower your risk.
  • Not having children.
  • Having a child after 30 years of age
  • Drinking more than 2 standard drinks of alcohol per day.
  • Gaining a lot of weight during adulthood, especially after menopause.
  • Smoking of any kind before the menstrual cycle begins (before 12-14 years of age).
  • The consumption of processed meats regularly.

Warning signs/symptoms:

Some of the early warning signs of Breast Cancer can include:

  • Lumps in the breast or around the underarm area.
  • Changes in breast size and/or breast shape.
  • Pain in a specific area of the Breast that does not eb.
  • More obvious veins that can be along the surface of the breast.
  • Sudden discharge from the nipples.
  • A scab or a rash on the nipple.
  • Swelling, redness, or darkening of or around the breast.
  • Inversion of the nipple
  • Inversion of other parts of the breast.

Some symptoms of inflammatory breast cancer:

  • Swelling.
  • Redness.
  • A pink, reddish purple or bruised appearance of the Breast.
  • A burning sensation.
  • Swollen lymph nodes in the collarbone or underarm areas.
  • Inversion of the nipple.
  • Ridged skin.
  • Pitted skin.
  • Rapid increase of breast size.

Diagnosis/screening/testing:

If a doctor wants to test that you have Breast cancer, they will carry out a Clinical Breast Exam (CBE). During this exam the individual suspected of having Breast cancer will have to remove all clothing from the top half of his or her body. There are two methods for this exam:

Visual Examination: They will ask the individual to raise and then lower both of their arms. This can show differences in the size and/or shape of the breasts. They will also check for any rashes, dimpling, or nipple discharge.

Manual Examination: The doctor will use the pads of their fingers to check the entire breast/s of the individual as well as their underarm and collarbone for any abnormalities and /or suspicious lumps. They will also check any enlarged lymph nodes.

If further testing is required there are also other forms to ensure a correct diagnosis:

Mammogram: An X-Ray of the breast and chest area, this will show any dark spots (growths) within the breast.

Magnetic Resonance Imagery (MRI): A scanning procedure of scanning to provide doctors with a detailed picture of the breast and chest area.

Biopsy: The doctor uses a needle or other extraction device to take a sample of tissue or fluid for further testing.

If a doctor recommends these tests, it does not necessarily mean that they have breast cancer, in most cases it will show that they do not have cancer at all.

Treatment

For an individual diagnosed with early stage breast cancer, multiple treatment options are available. These treatment methods include:

Breast Surgery: Surgery for early breast cancer involves either breast conserving surgery or mastectomy. Breast reconstruction may be possible after a mastectomy. Both types of breast surgery usually also involve surgery to remove of one or more lymph nodes from the underarms.

Mastectomy: Involves the removal of the entire breast (including the nipple) and usually one or more lymph nodes from the underarms.

Breast Conserving Surgery: Involves the removal of the cancer itself as well as a small portion of healthy tissue surrounding the tissue (known as a surgical margin)

Breast Reconstruction surgery: Surgery to rebuild a breasts’ shape after a mastectomy.

Radiotherapy: For people diagnosed with breast cancer, this method is almost always recommended after breast conserving surgery and only sometimes after a mastectomy.

This method uses X-rays to destroy cancer cells in some parts of the body (in this case, the breasts). This method is a localised treatment, meaning that it only treats the area of the body it is targeted towards.

Chemotherapy: This method is usually recommended for people diagnosed with Breast cancer that is suspected to have metastasized to other areas of the body. It can also lower the risk of breast cancer recurring after treatment as well as it increases the likelihood of survival.

This method uses various drugs to destroy cancer cells. As well as killing cancer cells, this method of treatment also destroys normal cells that are rapidly dividing. However, unlike cancer cells, regular cells have the ability to repair the damage and can recover over time.

Hormonal Therapies: This method is used on women whom have hormone receptors on their breast cancer cells. They can be used alone or alongside other forms of treatment.

Hormone Receptors: If a breast cancer cell has hormone receptors on it, it means that the cancer is caused by female hormones. If a woman’s cancer has hormone receptors, there cancer is known as “Hormone Receptor Positive” There are 2 main types of receptors, progesterone receptors (PR), and oestrogen receptors (ER).

It involves the consumption of drugs over a period of time and has been known to decrease the likelihood of cancer returning after the completion of treatment. They stop hormone receptor positive cancer cells from growing.

Targeted (Biological) Therapies: Involve drugs that halt the growth of certain types of cancer cells. This method is only suitable for some women. They may be used with other breast cancer treatments.

The most common targeted therapy used to treat early stage breast cancer is trastuzumab (Herceptin).

New Technology in Oncology

Ever since the Ancient Egyptian times, which is when the treatment of cancer (although it was not called that) in its earliest forms can be found to date back to (Approximately 3000BC), there has been a great deal of development and improvement when it comes to the field of oncology (the study of the development and treatment of cancer). From the development of chemotherapy in the 1940’s to vaccines being discovered to prevent specific cancers, the advancement of technology in regard to oncology is astronomical.

Vaccines for The Prevention of Cervical Cancer:

In 2006, Gardisil and in 2007, Cervarix®, both vaccines that are used in conjunction as a vaccine to prevent Human Papillomavirus (HPV), which is known to be a main co-efficient in the cause of cervical cancer, were certified by the FDA.

These vaccines were created to protect against the four most common types of HPV; HPV 6, HPV 11, HPV 16, and HPV 18. These strains of the Human Papillomavirus are known to be responsible for approximately 70% of cervical cancers internationally.

This form of vaccination (called in various locations by other names and brands) are administered by a needle three times over a period of six months to both males and females between 12 and 18.

Pap Smears for Early Detection of Cervical Cancer

George Papanicolaou (1883 – 1962) discovered the pap smear in 1928 while studying the cytopathology of the human reproductive system. He (debatably) discovered that there was a discernment between normal cells and malignant (cancerous) cells could be detected via observation through a microscope.

In 1943, he published his book “Diagnosis of Uterine Cancer by the Vaginal Smear”, by which his method soon became the gold standard of methods when it comes to detecting cervical cancer. This book described physiological changes the menstrual cycle as well as the influence of hormones and malignancy in vaginal cytology.

Pap smears have been proven to reduce the risk of developing cervical cancer due to the detection and treatment of cervical changes prior to development into cancer. Statistics show that 80% of cervical cancers occur in women who have never been screened or who have not had timely screening of their cervix.

The method involves the scraping of the cervix by an extraction device and the viewing and analysis of the cell sample under a microscope. This method is quick, efficient and cheap to conduct.

According to the US Preventative Services Task Force and the American Congress of Obstetricians and Gynaecologists, it is recommended that women begin getting pap smears at the age of age 21 and book another one every three years until the age of 65.

Mammograms and DNA Sequencing for Early Detection of Breast Cancer Risk: Mammograms and DNA sequencing, as previously stated (See “Breast Cancer”) are two very common methods used for the detection of Breast Cancer.

Mammograms are a low dose x-ray examination of your breasts that were invented in the 1960’s and developed further during the 1970’s. They can sometimes detect breast cancer before there are any signs or symptoms.

DNA Sequencing (Cancer Genome Sequencing), which first appeared in a study of several breast and colorectal tumours in 2006, is the whole genome sequencing of a sing, homogeneous or heterogeneous group of breast cancer cells, it is done to profile and note the changes (mutations) in the DNA of cancer cells. These changes, depending on their mutations, can lead to a specific form of treatment or therapy being recommended of the breast cancer patient.

This method is also used to determine whether or not specific genes can be found within an individual’s genetics such as the BRCA 1 and BRCA 2 genes, which are what a person has if they are likely to inherit either ovarian or breast cancer. Studies have shown that approximately 20 to 25 percent of women globally who are diagnosed with ovarian cancer have a hereditary tendency to develop the disease

Skin And Breast Cancer Prevention

Cancer is a global epidemic that takes millions of lives every year. There are many types of cancers but due to variables like the environment, there are certain ones on the rise. They can be developed through factors such as unhealthy diets, UV radiation, smoking, air pollution, etc. It is formed, in result, of a mutation of cancerous cells. In spite of that, there are ways to prevent the risk of developing one of these cancers. Some of these ways include a change of diet, an increase in physical activity, and quitting harmful habits.

In the article “Environmental and Occupational Causes of Cancer New Evidence, 2005–2007”, the author discusses specific types of cancers, such as brain, lung, and breast, and how one might be at risk to acquire it. For example, one cause of brain cancer mentioned is cell phones. This is due to the radiofrequency fields that are given off by phones (Clapp, Jacobs, Loechler, 2005-2007). In today’s society many people, especially young adults, carry a mobile device with them at all times. Cell phones are used on a daily basis by many and it one of the primary forms of communication. In the publication of “Ultraviolet radiation and skin cancer” it is said that skin cancer is a common type of cancer and it is mainly caused by UV radiation. It can also be caused by tanning beds in a more unnatural setting. Long term exposure to the sun without protection can be dangerous. For example, basal cell carcinoma, a form of skin cancer, is found in areas of the skin that are directly exposed to the sun such as the head and neck. Also, Melanoma, which is also a type of skin cancer, causes 75% of skin cancer deaths (Narayanan, Saladi, and Fox, 2010). Alcohol is consumed by millions of people all over the world on a daily basis and if it is consumed in excess amounts it can lead to the development of a cancer potentially in the throat, liver, esophagus and mouth. At about 50 grams a day, the chances of developing a form of cancer triples. Another one of the most controllable yet common forms of cancer is caused by smoking. In total, at least 30 percent of all cancers are induced by smoking. Even if a person does not develop a form of cancer from smoking, their life expectancy is shortened by 13-14 years (Cengage Learning, 2018). Breast cancer is a very common cancer in women more than men, about 40,000 deaths are caused by breast cancer. On average, every two minutes a woman is diagnosed with breast cancer in the United States. Breast cancer also represents 15% of all cancer cases in the United States. One in eight women will develop breast cancer at some point in their lifetime. Although breast cancer is much more common in females, males can also develop this cancer. However, the risk is much slimmer and every one in 1,000 men develop it (National breast cancer foundation,2019).

Cancer development is a multi step process which involves genetic mutations that some people can not control. Cancerous cells can develop from normal, fully functioning cells and once the cell stops functioning properly the cancer spreads and begins growing uncontrollably. However, people can be born with a mutation and nothing will come of it. For the cell to become cancerous, it has to have gone through multiple mutations. The mutations take time so for this reason people of older age are more likely to develop a type of cancer (The Dr.Susan Love Foundation, 2019). Some cancers can develop as a result of genetics. In fact, genetics are the primary cause in 5-10 percent of all cancers (Cengage Learning, 2018). If someone in a person’s family had cancer in their lifetime, it is possible for that to be passed down. For example, breast cancer can be genetically passed down in women in some families.

According to the article “Physical Activity and Cancer Prevention— Data from Epidemiologic Studies” written by I-Min Lee, the author states that a way to prevent cancer from occurring or developing includes physical activity. Lee had discussed a study in her writing called the Harvard Alumni Study in which men were followed up for up to 26 years. Men who participated in sports and other physical activities and those who were less active. The study showed that men who were more physically active were less prone to develop colon cancer (Hsieh, Lee, Paffenbarger 1991, as cited in Lee, 2003). The study also took notice of the development of prostate cancer and concluded that men who participated in more extreme exercise were at less risk (Hsieh, Lee, Paffenbarger 1992, as cited in Lee, 2003). In the article “How can we prevent cancer?” by Carlo Croce, the author discusses multiple ways a person can change their lifestyle to be less prone to cancer. It is said that eating fruits and vegetables regularly can be beneficial due to the antioxidants and vitamins that they posses. Avoiding cancer causing factors such as tobacco, covering up at the beach, or using sunscreen is also a way to remove the risk of developing cancer (Croce, 2001). A healthy diet is crucial to cancer prevention. Adopting a predominantly vegetarian diet and eating vegetables will greatly reduce one’s chances of developing a form of cancer. Consuming tea, which has the phytonutrient polyphenol, creates a natural antioxidant that can block the formation of nitrosamines and activates carcinogens. However, the first and most important step in cancer prevention is education. If an individual is not aware of how one can develop cancer, how it can occur, or how to prevent it then they will be at a higher risk of getting cancer (Cengage Learning, 2018).

In conclusion, cancer is a dangerous attack on an individual’s body that causes mutations in genetics and causes tumors to form. There are many different forms of cancer with some being more prevalent than others such as skin cancer or lung cancer. While there is no definite cure for cancer, there are ways a person can prevent the risk of developing it in their lifetime. By taking the first step and becoming educated about what cancer is and learn about healthy life choices, one may decrease their risk of getting it. Some healthier life choices people should incorporate into their daily life are exercise and an appropriate diet. These choices among others, such as quitting life threatening activities like smoking and sunbathing, can prolong an individual’s life and help with cancer prevention.

References

  1. Breast Cancer Facts. (2019). Retrieved from https://www.nationalbreastcancer.org/breast-cancer-facts.
  2. Clapp, R. W., Jacobs, M. M., & Loechler, E. L. (2008). Environmental and Occupational Causes of Cancer: New Evidence 2005-2007. Reviews on Environmental Health, 23(1), 1–38. doi: 10.1515/reveh.2008.23.1.1
  3. Croce, C. M. (2001). How can we prevent cancer? Proceedings of the National Academy of Sciences, 98(20), 10986–10988. doi: 10.1073/pnas.221453098
  4. How Cancer Develops. (n.d.). Retrieved from https://drsusanloveresearch.org/now-that-you-know-about-dna-rna-and-proteins-its-time-to-learn-about-the-cell-cycle/.
  5. Lee, I.-M. (2003). Physical Activity and Cancer Prevention-Data from Epidemiologic Studies. Medicine & Science in Sports & Exercise, 35(11), 1823–1827. doi: 10.1249/01.mss.0000093620.27893.23
  6. Narayanan, D. L., Saladi, R. N., & Fox, J. L. (2010). Review: Ultraviolet radiation and skin cancer. International Journal of Dermatology, 49(9), 978–986. doi: 10.1111/j.1365-4632.2010.04474.x

Evaluating the Impact of Obesity on the Treatment and Recurrence of Breast Cancer

Introduction

The second biggest cause of cancer in the UK is overweight or obesity and this is preventable. Cancer Research UK (CRUK) reports that breast cancer is now the UK’s most common cancer. (CRUK, 2019). According to the World Health Organisation, (WHO) breast cancer is the second most common cancer in the world. WHO have also now estimated that in the last 40 years, the prevalence of obesity worldwide has more than doubled (WHO, 2018). It is expected that cancer incidence is to rise further if the recent trends in overweight and obesity prevalence continue (CRUK, 2019). It has been reported that the worldwide cancer incidence and mortality rates are reflective of the prevalence in overweight and obesity (CRUK, 2019). Taking into account the current obesity epidemic (Flegal et al. 2012), the effects obesity has on the incidence of cancer and the lower standard of outcomes in patients with cancer seem particularly important. Researching the link between cancer and obesity is essential as being obese is a potentially modifiable factor through changes in lifestyle, exercise and if necessary, medication (Cho et al. 2018). Obesity has been associated with an increased risk of post-menopausal breast cancer. Obesity also has been found to cause several complications in the diagnosis and treatment of breast cancer. There is an increasing amount of evidence that obese breast cancer patients are more susceptible to complications related to surgery, chemotherapy and radiation (Lee et al. 2019). Recent evidence from a systematic review suggests that the risk of recurrence or death is increased by approximately 30% in obese women diagnosed with breast cancer (Chan et al. 2014).

Recurrence

The risk of recurrence is increased in breast cancer when the patient is obese. Minimal residual disease (MRD) is one way in which cancer recurrence can arise. Recurrence also comes about because of a collection of residual tumour cells, which happen to survive the primary treatment given to cancer patients (Denmark-Wahnefried et al. 2012). Most of the deaths that result from breast cancer are because of the inability to successfully prevent recurrence of a tumour (Loi et al. 2005). There are a range of non-biological and biological factors that reflect the association between the increased risk of recurring breast cancer and obesity. These include delayed detection which then leads to the presentation being at a more advanced stage at diagnosis (Loi et al. 2005). The chemotherapeutic agent doses used are sometimes not according to body size and this is another factor, also risks of second primary cancers are increased and causes of death not related to cancer (Ecker et al. 2019).

Biganzoli et al. (2017) conducted a study which investigated if being severely overweight or even obese at diagnosis, which was reflected by the patient’s increased body mass index (BMI), could be related to patterns of breast cancer recurrence. The study looked at the patterns of recurrence over time after the patient’s primary cancer treatment. The recurrence dynamics of breast cancer patients have previously been explored many times and the results showed that there was a multi-peak pattern. The pattern is defined by a high peak which begins early as a steady incline and then peaks at around the second year. This is then followed by a smaller and more delayed peak at around 5 or 6 years (Demicheli et al. 1999).

The results for breast cancer patients of normal weight are as expected showing the multi-peak pattern discussed above. The first early peak is clearly visible at 2 years (24 months), however the smaller peak at about 5-6 years (60-72 months) is partly distorted due to the first peak being very dominant. The pattern for obese patients differs from the normal weight patients as the first peak is displayed at a much higher risk level. The first peak is followed by a cluster of delayed late distant events.

It is thought that the hazard rates following this stable pattern over time in normal weight patients can be explained by the primary tumour surgery. This surgery may possibly result in the primary tumour/metastasis homeostasis being removed (Cornez et al. 2017). The surgery could also cause disruption of tumour dormancy, which then leads to the synchronisation of metastatic growth (Desmedt et al. 2017).

It has been hypothesised that the patients increased BMI, and therefore adiposity at diagnosis, could be influencing the breast cancer dormancy. Recent papers have supported this idea and have demonstrated that activation of dormant tumour cells was prompted by inflammatory marker or by abnormal fatty acid metabolism (Pascual et al. 2017). These processes are both present in overweight and obese patients. There is clearly a difference in recurrence dynamics between normal weight, overweight and obese women. However, when comparing the overweight and obese women, the recurrence dynamics of obese women is not an extreme or more intense pattern of the overweight women. This shows that the disparity observed in recurrence dynamics between overweight women and obese women does not simply indicate different degrees of the same biological process (Fornili et al. 2017). If this was to be the case, then the results would have shown a progressive change in recurrence risk across BMI categories.

Endocrine Therapy

Endocrine therapy is of major therapeutic value for patients with hormone receptor positive breast cancer, which is also known as oestrogen receptor positive breast cancer. Endocrine therapy lowers levels of oestrogen and reduces the growth of the cancer. This therapy aims this by either inhibiting the production of oestrogen or blocking the effect of oestrogen on a receptor level. There are several different classes of endocrine therapy and they all achieve the aim of endocrine therapy in different ways. The two most common classes of endocrine therapy used are selective oestrogen receptor modulators and aromatase inhibitors (Awan and Esfahani 2018). Other classes include selective oestrogen receptor down regulators, luteinising hormone releasing agonists, high-dose oestrogens and targeted therapies (Reinbolt et al. 2015). According to the BNF and NICE guidelines (2019) tamoxifen, which is a selective oestrogen receptor modulator, is recommended as the initial adjuvant endocrine therapy for men and premenopausal women with oestrogen receptor positive invasive breast cancer. An aromatase inhibitor, for example anastrozole, should be given as first-line treatment in postmenopausal women with oestrogen receptor positive invasive breast cancer. Aromatase inhibitors work by blocking the aromatase enzyme from converting androgens to oestrogens. This then prohibits the growth of new, residual, or dormant breast cancer cells. In the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, it was found that there were significant improvements in breast cancer outcomes in women taking Arimidex versus tamoxifen (Tremont et al. 2017) Arimidex is a brand name for the drug Anastrozole. Across all BMI levels, tamoxifen was found just as effective as Arimidex with regard to overall recurrence. This suggests that obesity had no effect on the effectiveness of tamoxifen (Sestak et al. 2010).

An 8 year follow up was conducted and it was found that almost 20% of women using Arimidex had breast cancer recurrence (Azrad and Denmark-Wahnefired 2014). Compared to patients who were of normal weight, obese women were much more likely to experience distant recurrence and disease recurrence. It was also reported that obese women with breast cancer had a significantly increased recurrence rate, this included overall and at distant sites. This suggested that the suppression of the aromatase enzyme by Arimidex could possibly not be entirely effective in postmenopausal women who are obese (Howell et al. 2005). In another trial, the results for treatment with anastrozole showed significant differences when looking at the risk of recurrence and even overall survival in normal weight women and obese women. In additional analysis, obese women taking anastrozole tended to have a much greater risk for reduced disease-free survival compared to obese women who were taking tamoxifen. The data collected form these studies collectively show a worse prognosis for obese women being treated with endocrine agents (Lee et al. 2019). They also suggest that AIs may be of reduced effectiveness than tamoxifen in this group of patients.

Other treatments

Surgery is another treatment option for breast cancer patients. Obesity is a known cause of complications with mastectomy, causing both minor and major surgical complications such as increased risk of bleeding and infections (Garland et al. 2018). For chemotherapy, recent guidelines have recommended administrating the full weight based doses for obese patients rather than using ideal body weight. This has been based on studies that have showed reduced survival rates in obese patients which is due to the under-dosing of cytotoxic therapies (Argolo et al. 2018).

Conclusion

In conclusion, breast cancer patients who are obese illustrate a unique patient population. From many studies, it is known that are at a higher risk for breast cancer development and experience more difficulties with surgery and therapy. Even with appropriate treatment, they still have an increased recurrence risk compared to women of normal weight. Furthermore, endocrine therapy in obese women has proven to be less effective, and there is the idea that tamoxifen is of more effectiveness than AIs in obese patients. Taking all this into account, obesity is often an indicator of an unhealthy lifestyle consisting of excess intake of saturated fats and unsatisfactory levels of physical activity. These are now being recognised as risk factors for worse prognosis of cancer. Based on these challenges, more investigations are needed to assess the effective treatment mechanisms required to successfully target breast cancer in the obese women population.