EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018

Introduction to Symptoms, Risks Factors, Treatment and Management

Ebosetale Blessing Ikhuoria, Christian Bach

 manner. Better remedial alternations and significant Abstract—This paper aims to review current research and improvement in general wellbeing, public health and care advancement in prevention and management of breast . have resulted in impressive reduction in mortality and a Occurrence of has increased globally in the last major increment in lifespan longevity. Breast cancer decade. It been recorded that 15% of cancer-specific breast uncommon in men, constituting 1% of all breast cancer cancer. It is a comprehensive literature review on Breast cancer and its dependent variables created a theoretical analyze and diagnoses in the united states and below 0.1% foundation of the paper. Using the review-centric theory, a of cancer related death in men. The type of breast cancer is model was developed and presented to encapsulate the important in determining the most effective treatment knowledge of the benefits associated with exercise on breast approach[12]. Hormone Receptor-positive breast cancer is cancer outcomes through adiposity and immunological the most common type of breast cancer, which account for mechanisms. The model highlights breast cancer and its about 75% of all breast cancer. This cancer category grows relationship with immunological biomarkers, obesity-related biomarkers, exercise or physical activity, biomarkers for in reaction to the hormones and progesterone and adiposity. However, more research is needed to understand the as such considered to respond to therapies that intend and use of low doses of radiation inadequate screening, sometimes a restrain the development of these hormones[17]. HER2- screening test may not be able to show with certainty that there positive breast cancer is another type of breast cancer is no cancer, or occasionally may miss breast cancer. classified by the system, it is epitomized by cells that Overtreatment, some breast that are found by produce high amount of protein known as HER2/neu. It would never become a health problem in the woman’s lifetime. False negatives, other test results miss breast exhibits 20-30% of Hormone Receptive-positive breast cancer. This shows how signs and symptoms of breast cancer, cancer. HER2-Negative are depicted cancer that do not over causes and risks factors associated with breast cancer, enunciate HER2/neu [18]. It represents 20–30% of Hormone treatment of breast cancer and the management of breast Receptor- Positive breast cancers [19]. Tumors that do not cancer malignancy can help in the decreased of mortality rate overexpress HER2/neu are described as HER2-negative in woman and men who has and are likely to test malignancy to [20]. Breast cancer is a disease that has various symptoms breast cancer disease. but is mostly detected at a later stage. Outlining and Index terms— Breast Cancer; Signs and symptoms; Breast understanding the molecular and biochemical mechanism Pain; ; Treatment; Therapy; Endocrine Therapy; that underlies the role of some risk factor both genetics and Nipple Retraction; Lump; ; H90 inhibitors; environmental factor in breast cancer aid screening, Genetic Mutation; Malignancy; Body mass; Medication usage treatment planning and prevention of the diseases thus in a way decrease the high mortality and modalities associated with the disease. There is a lack of research pertaining I. INTRODUCTION Triple negative breast cancer (TNBC), is a subtle form of There is a growing literature on breast cancer overview breast cancer, which is known as a sub type of HER2- characterized by the uncontrolled growth of abnormal cells negative cancer. TNBC indicate malignant cells, where [1]-[10]. Breast cancer is an individual tragedy for those estrogen and progesterone receptors are deficient or affected. It is a highly curable disease when detected early, destitute, these cells also do not over expressed the HER2 and an inevitably mortal disease when discovered too late proteins TNBC account for about 15% of breast cancer, and [11]. Breast cancer is described by recalcitrant growth of it is belligerent and more rigid to treat, as it counter and malignant cell. In the epithelial tissue of breast male and never respond to standard treatment. Due to the female could be affected by these diseases. Breast cancer aggressiveness of this type of breast cancer, it is more has been accounted as the most common cancer in women essential to treat patient early. However, with few effective in the world, which ascent vividly with age. 29% of new treatments feasible there is high-negative therapeutic need. cancer cases is breast cancer and 14% of all cancer death related in the world among women in 2012. This analysis II. RESEARCH METHODOLOGY shows that 1.7 million new cancer cases in women and Review Centric Research about 522,000 deaths in 2012 [15]. As dangerous as its might appear, the mortality to occurrence incidence A comprehensive literature review on Breast cancer and proportion more benign than pancreas and liver cancer, with its dependent variables created a theoretical foundation of proportions of 0.98 and 0.95, respectively termination of the paper. Using the review-centric theory, a model was developed and presented to encapsulate the knowledge of the benefits associated with exercise on breast cancer Publised on July 31, 2018 E. B. Ikhuoria and C. Bach are with University of Bridgeport, USA. (e- mail: [email protected])

DOI: http://dx.doi.org/10.24018/ejers.2018.3.7.745 58 EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018 outcomes through adiposity and immunological IV. SIGNS AND SYMPTOMS mechanisms. The research about signs or symptoms of breast cancer This review paper shows how signs and symptoms of has been helped to reduce mortality rate of the disease, breast cancer, causes ad risks factors associated with breast female and male who are susceptible to this disease can self- cancer, treatment of breast cancer and the management of evaluate themselves before going to the doctor but breast cancer malignancy can help in the decreased of nevertheless doctors have to perform various test to approve mortality rate in woman and men who has and are likely to malignancy or benign of breast cancer. Common symptoms test malignancy to breast cancer disease. This review paper of breast cancer are change in look or feel of the breast, shows how signs and symptoms of breast cancer, causes ad nipple and nipple discharge, doing examination of breast risks factors associated with breast cancer, treatment of regularly help detect these symptoms immediately to breast cancer and the management of breast cancer prevent growth of disease, redness or scariness of the nipple malignancy can help in the decreased of mortality rate in or breast skin, or a discharge are also symptoms [21]. woman and men who has and are likely to test malignancy Previous surgery has effect on breast cancer as these women to breast cancer disease. might experience late symptoms and this is caused by around the chest wall and shoulder [22]. Palpable III. BREAST CANCER lump, mass, thickening tissue, irregularity that feels The research has been regarding breast cancer around the distinctly different from surrounding tissue, should be world. Breast has been done in various identify as signs and symptoms during lifespan [23]. stages, because of the way that malignancy has distinctive Various machines are used to detect breast cancer in stages from early recognition to substantial development of women, diagnostic mammography is commonly used for the tumor. These growths develop in the breast tissue and it women who have showed common signs [24]. A change in a is seen in women mostly and it has high death rate but breast wart or mole is a warning sign and symptoms, identify by cancer malignancy is seen in men and women [13]. thickening or lump on body, unexplained weight loss and a Different difficulties happen amid and after cancer because change in bowel or bladder habits [25]. Data suggest that various medical teams work together to stifle/destroy the sexual dysfunction and hormonal symptom are prevalent in tumor for the body [86]. Breast cancer malignancy causes male cancer breast survivor (Ruddy et al., 2013). According most death in underdeveloped countries around the world in to all the researchers and authors all signs and symptoms female and its changes human way of life and method of have been seen and demonstrated in cancer patient and living due to the screening involved [83]. theses sign has help to reduce the mortality rate of women recreate wildly by prompting in-situ , which across the world. makes it to attack the typical tissue. Pathologist classified A. Breast lump cancer into subtypes based on glandular or ductal units [82]. Uneasiness in human conduct that is mental and physical Breast lump was the most common symptom, recorded in misery state of mind as a result of the threat related about four-fifths of all women (83%). The next most mortality [95]. As explained before that breast cancer commonly reported presenting symptoms were nipple malignancy are described into 3 sorts: HR positive, human abnormalities (7%), breast pain (6%), and breast skin epidermal development factor receptor 2 positive (HER-2), abnormalities (2%) [26]. The classic symptom for breast and triple-negative cancer diseases these sorts depend on the cancer is a lump found in the breast or armpit [27]. immunohistochemical properties of the body and tumor B. Nipple retraction [93]. Breast tumor is dangerous however because of its Breast self-examination (BSE) is a significant way to be mindfulness and research, researcher have possessed the to be familiar with the size of the breast, skin condition of capacity to turn out with treatment to help deal with the the breast, cyclical changes and breast texture [28]. Alerting ailment in this way decreasing death rate and furthermore features of breast cancer generally known are such as pain in help in destroying the sickness after early detection. nipple, persistent breast tenderness, discomfort or unusual breast pain, bloody or clear nipple discharge, scaly or pitted skin on nipple, lump mass or swelling of the breast, swelling in the armpit lymph nodes, inverted retracted nipple, scaly or pitted skin on nipple [14]. Metastatic advanced stage diseases, bone pain, bone metastases, shortness of breath, neurological pain or weakness are symptoms present in underarm lymph nodes disease [29]. C. Change in breast shape The size or shape of the nipple might be affected by natural changes or any changes in the body weight [30]. However, a situation whereby the nipple retract goes in and

Fig. 1. Breast cancer and its components doesn’t return to its normal shape can be as a result of breast cancer [31]. With the aid of mammogram or ultrasound, problem with the milk ducts situated below the nipple surface and areola may be diagnosed [32]. Changes in the breast size and shape after puberty may be a symptom of the

DOI: http://dx.doi.org/10.24018/ejers.2018.3.7.745 59 EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018 swelling of the milk ducts or lobes deep within the breast factors put inconsideration when one is tried harm to bosom and can be due to regular monthly hormonal cycles, growth. fibrocystic breast cancer or a warning sign of a more serious A. Genetic mutation disease [33], [34]. BRCA1/2, the DNA repair associated BRCA1 gene D. Breast Pain product is a nuclear phosphoprotein that participates in the If you are having breast pain, note whether or not it is DNA damage response, cell cycle [36]. The lifetime risks of changing with your monthly period, and if it is present in breast cancer are as high as 80%, among women carrying one or the two . Even though it feels normal, it can be BRCA1 mutations, with a higher frequency of cancer risk at uncomfortable and it might not be worrisome [35]. younger ages. Male carriers of BRCA pathogenic variants However, in a situation where the pain occurs in one breast, have an increased risk of prostate cancer, and those with armpit or off-cycle, it is advisable to get checked. Also, BRCA2 pathogenic variants also have a significantly keeping a good menstrual cycle record might help to increased lifetime risk of developing breast cancer of about understand changes in the hormone in the breast and will be 6% [37]. Family history is a well-known risk factor of BC, useful for doctors in diagnosing what is wrong in the body depending on the number of cases, on ages of the BC, and [12]. on the cases’ degree of relatives. Compared to women without any first degree relatives with BC [38]. There are a number of identified high-risk breast cancer susceptibility genes, including BRCA1, BRCA2, PALB2, TP53, CDH1, and PTEN [39]. B. Body mass Environmental factors can also initiate the occurrence and progression of breast cancer [40]. High body mass index (BMI) could also increase risk of post-menopausal breast cancer and a negative outcome in those with breast cancer history. Breast density is predictive factor of breast cancer risk. A review concluded that women with breast that contains 60-75% dense tissue are 4-6 greater risk of

Fig. 2. Signs and symptoms of breast cancer developing breast cancer when compared to those without dense tissue. However, women that have high BMI have a low breast density, even when increase in BMI corresponds V. RISK FACTORS with increase in breast cancer risk. BMI becomes a stronger The findings have been carried out about risk factors and predictive factor of breast cancer risk if the density of the its part in breast cancer disease. In spite of the fact that the breast is controlled in analyses [41]. exact reasons for breast cancer are vague, we know the C. Diet/Nutritional state principle chance elements. All things considered, most There is increasing evidence that dairy protein and milk women considered at high risk for breast disease don't get it, intake increases circulating IGF-I level, which is linked to while numerous with no known risk factors do develop breast cancer. Dairy intake mainly milk could negatively breast cancer malignancy. Among the most significant affect breast cancer risk factors like: height, number of factors are propelling age and a family history of breast menstrual cycles and birth weight of the mother and her cancer. 10% of all malignancies among ladies worldwide is children through IGF-I [42]. The mechanism proposed for breast cancer which makes it the most widely recognized the effect of dietary fat on BC involves increased estrogen sickness however risk factors are to help or show if anytime production in adipose tissue which causes inflammation and in ones life there will be odds of having breast cancer [84]. modifications in some physiologic processes leading to Risk factors which includes constant irritation, corpulence higher risk of BC [43]. Among vitamin D containing foods, and metabolic brokenness, rest shortage [94]. Pubescence occasional consumption of eggs was associated with lower stage may be considered a risk factor also because of the risk when compared with twice to once per month but fact that the time at which the main mensuration and labor higher when compared with daily to once per week. can make one helpless to the ailment [87]. As early Occasional consumption of mushrooms was found to be detection can help the multidisciplinary group to destroy the significantly associated with higher risk of BC compared to disease however look into has demonstrated that liquor daily consumption. Alcohol consumption increases the risk utilization can cause repeat of breast cancer particularly in of breast cancer up to age 70 by 7% [44]. postmenopausal ladies [92]. Risk factor of breast cancer, contingent upon the quantity of cases, on periods of the D. Drug/Medication usage bosom malignancy, and on the cases' level of relatives, Pharmacotherapy are the use of contrasted with ladies whose family relatives never had first antiestrogens (, raloxifen) reduces the risk. Due to degree growth [42]. Other risk factor elements can likewise side effects, the use should be restricted to high-risk women be considered, utilization of oral contraceptives and with a strong family or mutations in breast utilization of menopausal hormone treatment [81]. Hazard cancer-susceptibility genes. Radiation exposure dose of 4Gy factors as clarified by the creators are for the most part delivered to the breast was associated with a 3.2-fold

DOI: http://dx.doi.org/10.24018/ejers.2018.3.7.745 60 EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018 increase in the risk [44]. Women in either their primary therapeutic target, and the mTOR inhibitors have been tested childhood residential road or cross street nearest to their in many clinical trials. In the phase II TAMRAD trial, the primary childhood residence was divide by a barrier had a addition of everolimus to tamoxifen markedly prolonged moderate increment in breast cancer risk. Combined PFS and OS in patients with AI-resistant metastatic breast analysis suggested a high exposure to traffic-related cancer [46]. Its been demonstrated that the expression of pollutant and that is associated to the overall increment in estrogen responsive genes (PGR, GREB1, TFF1 and breast cancer, post-menopausal breast cancer, and invasive PDZK1) was higher at times in the menstrual cycle when ER- breast cancer risk [40]. the estrogen levels would be expected to be high and low when estrogen levels would be at their nadir. If the expression of responsive genes is affected by circulating hormone levels then measurements of sex hormones may ultimately provide a marker for endocrine sensitivity, and hence disease outcome, after treatment with endocrine agents [47]. B. Hsp90 Inhibitors Pharmacological inhibition of Hsp90 shows great promise in the field of breast cancer treatment because Hsp90 inhibitors have the potential to suppress multiple oncogenic signaling pathways simultaneously, thus reducing the possibility of molecular feedback loops and mutations leading to tumor resistance [48]. HSP90 is a molecular

Fig. 3. Risks factors of breast cancer and its derivatives chaperone involved in the structural maturation of various ‘client proteins’ including EGFR, AKT, PI3K, as well as components of the homologous and non-homologous DNA VI. TREATMENT AND THERAPY repair pathways (e.g. BRCA1, RAD51). Thus, HSP90 The exploration done on breast cancer treatment and its inhibition has the potential to inhibit multiple signaling part in breast cancer. There is different treatment breast cascades regulating growth, proliferation and survival. Two cancer despite the fact that their strength be repetitive of the ongoing phase I clinical trials are evaluating HSP90 tumor, Treatment will rely upon; Chemotherapy can be a inhibitors for advanced TNBC in combination with olaparib possibility for breast cancer malignancy, the kind of breast or paclitaxel [49]. cancer, the phase of the tumor, affectability to hormones the C. Chemotherapy patient's age, general wellbeing, and inclinations. A major treatment approach to breast cancer is Glucocorticoids treatment and studies have demonstrated chemotherapy, which has significantly extended patient life that they may have antagonistic effect on treatment expectancies [50]. Because of the different etiologies of the achievement [89]. A large number of female have access to side effects of chemotherapy patients may encounter a diagnotics due to less surgries as surgeons embraced the certain degree of behavioral difficulties when managing multimodality approach to breast cancer treatment and led their symptoms [51]. TNBC is characterized by higher multidisciplinary team (MDT) working [45]. Tumor markers relapse rates compared with ER-positive breast cancers, are use in counteractive action, screening, treatment and with a predilection to metastasize to brain and lungs along observation of Breast disease, whereby 13 classes of bosom with loco regional recurrence and lower incidence of tumor markers were mulled over [85]. There are different metastases to bone, liver and non-regional lymph nodes. In a types of disease and metatistics breast cancer is considered meta-analysis study platinum-based chemotherapy in breast as an in reparable one because of its treatment modality cancer patients with TNBC showed an improved short-term [88]. Treatment of breast cancer tumor additionally efficacy compared to the non-TNBC group during neo- incorporate radiation treatment due to its transformative adjuvant chemotherapy, but is yet to be demonstrated in the effect as this will enable ladies with beginning time ailment advanced breast cancer setting [52]. The other problems to keep up uprightness of their body in like manner those included constipation, diarrhea, and stomach discomfort. with cutting edge ailment to have help from agony [91]. Patients let nature take its course, used prescribed Registered Tomography and Ultrasound can't be solid amid medicines, or increased dietary fiber to attempt to rectify the removal procedure, MR has the capability of measuring their symptoms [53]. temperature and giving observing, however this capacity is constrained by a few other pragmatic contemplations, D. Surgery including the trouble of utilizing radiofrequency or The best approach to achieve local control in TNBC or microwaves in a MR machine [90]. The fundamental any solid tumor is surgery. Studies were undertaken to choices for treatment of breast cancer incorporate radiation assess the surgical methods that patients chose, either treatment, surgery, organic treatment, or focused on sedate or , and it was found that the triple treatment, hormone treatment. negative status does not influence their choice [4]. Given the A. Endocrine Therapy aggressive nature and high relapse rates associated with TNBC, it has been of concern whether conservative surgery The PI3K-AKT-mTOR pathway is an important is safe in this group of patients. A recent observational

DOI: http://dx.doi.org/10.24018/ejers.2018.3.7.745 61 EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018 review concurs that TNBC patients tend to present with patient, Clinical data such as Tumor location, Tumor size, higher-grade tumors and higher rates of nodal positive Connection to the nipple, Connection to the skin and the disease. However, when comparing across tumor size and thorax wall, Stage of regional nodes [80]. Instrumental data grade, TNBCs exhibit lower involvement [52]. such as Presence of multiple Tumors focuses in the same quadrant or in different ones, distribution and location of micro-calcifications and dimension of interested area needs to be known [16]. There are of course other factors that might influence treatment selection in older women including psycho-social issues, differences in pharmacokinetics including drug absorption, hepatic metabolism, renal function, differences in pharmacodynamics including drug elimination, differences in normal tissue toxicity including impaired bone marrow reserve, impaired mucosal protection, impaired cardiac function, impaired neurological function, performance status and last but by no means least patient preference [59].

C. Cell-Target Suicide Fig. 4. Treatment and therapy of breast cancer and its components The transformation of s pro-drug to toxic metabolite via genetic engineering of tumor cells is a fascinating means of creating an artificial diversity between a normal and VII. MANAGEMENT neoplastic [60]. Higher chance in destroying malignant cells The research done involving management of breast can be achieved by transferring gene that is present normally cancer and its role in patient who test malignancy to breast in human instead of endogenous gene overexpression. A cancer. is carried out by a model for this approach used HSV-1 thymidine kinase gene. various team of breast specialists including surgeons, The gene is given in combination with ganciclovir which is radiologists, pathologists, breast cares nurses and a prodrug in a way different from mammalian thymidine clinical/medical oncologists, breast cancer patients now kinase. The phosphorylated ganciclovir eventually fuses into receive individualized treatment plans that may include DNA thus inhibiting the synthesis and transcription of DNA. surgery to both the breast and axilla [54]. Breast cancer The effectiveness and safety of this method has been tested occurs both in women and in men, but breast cancer is men in many clinical trials that involve multiple malignancies are relatively uncommon but its incidence has been rising. [61]. Traditionally, the Management of Breast cancer in men is D. Gene therapy based on extrapolation from clinical trials of breast cancer in women, due to the much more extensive data available in It is generally accepted that cancer arises because of an women with this disease [55]. Host differences that affect accumulation of multiple molecular genetic defects that end the Management of Breast cancer for young patients up in a cellular phenotype categorized by disregulated including being premenopausal at diagnosis, fertility, growth. Different strategy of gene therapies has been genetics, and social/emotional issues in particular should be developed as prospective new cancer therapies. The present considered early in the course of their care [56]. The proto- and tumor suppresser gene knowledge in Management of Breast cancer within ectopic breast tissue is malignancy genesis has triggered gene therapy development similar to breast cancer identified within the true breast, and tactics aimed at ablating such gene [62]. Finally, immune tumor, node, metastases. system modulation can activate anticancer drug defense mechanisms.[63]. A. Psychological Factor Women with breast cancer suffered from emotional problems, especially for the anxiety issue, from diagnosis to 4 months after diagnosis. Anxiety was proposed as an important psychological factor during the time of diagnosis and active treatment period [57].These distressing symptoms not only affect patients at diagnosis and during cancer treatment but also persist years beyond the end of treatment. Given the growing number of breast cancer survivors and the impact of receiving a cancer diagnosis and undergoing treatment on mood and quality of life, it is important to understand cancer-related mental health symptoms to inform treatment and prevention efforts [58] Fig. 5. Management of breast cancer and its component

B. Treatment Options In the order to select the most suitable treatment for each

DOI: http://dx.doi.org/10.24018/ejers.2018.3.7.745 62 EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018

VIII. OTHER ASSOCIATED COMPONENTS

TABLE I: ADDITIONAL FACTORS THAT CONTRIBUTE TO BREAST CANCER Additional Factors Contribution to Breast Cancer Signs and symptoms “Radionuclide bone scan, abdominal sonography or other image studies were performed if specific symptoms, signs 1. Expression in Breast Cancer or elevated serum alkaline phosphatase level were noted [64] p. 287.”

Associated factors in breast “The greater breast cancer-related symptoms are side-effects, symptoms relating to breast and arm, and hair loss, 2. cancer were associated with the changes in flatter diurnal cortisol slopes during14-month follow up period [65] p. 96.”

Predictors of symptom “Symptom distress may generate physical dysfunction and emotional disturbances, particularly typical symptoms 3. distress in breast cancer such as upper- arm problems, sleep disturbance, fatigue, and body image disturbance, which develop gradually into patients long-term side effects. [66] p. 245.” Risks factors “Risk factors for MBC are generally the same as in women (e.g., advanced age, family history, chest wall irradiation, risk 1. BRCA 1 and 2 gene mutations), but include gender-specific causes of hypo- gonadism, such as Klinefelters, and factors oestrogen treatment for prostate cancer [67] p. 1079.”

Risk of breast cancer “Several forms of breast cancer are estrogen sensitive, with established hormone-related risk factors such as age at 2. menarche and , oral contraceptives, and hormone therapy use [34] p. 137.”

Screening for familial cancer “Only the Gail modified and the Tyrer-Cuzick models include familial and individual risk factors such as, age at 3. risk menarche, age at menopause, parity, age at first term pregnancy, BMI, history of LCIS, history of atypical [68] p. 70.”

Treatment/Therapy

“The transition from treatment to survivorship has been described as a conflicted experience where women try to 1. Treatment transition balance feelings of gratitude or happiness for getting through treatment for breast cancer with the demands of persistent physical symptoms, uncertainty, anxiety, mood changes, and fears of recurrence [69] p. 178.”

“It is important to stress that any diagnostic exam is only justified if therapy can be given: WB-MRI for cancer Breast cancer in pregnant staging is therefore justified in the second and third trimester, when anticancer chemotherapy can be safely given, 2. women treatment while it would be a futile maneuver in the first three months, when the risks associated with chemotherapy are

excessive and diagnosis would not lead to treatment w[70] p. 180.”

Breast cancer therapy “Beyond allowing patients who may not otherwise be candidates to have breast conserving surgery, neoadjuvant 3. chemotherapy provides a platform for in vivo evaluation of a breast cancer's response to therapy [71]p. 2.” Management

“Guidelines for behavioral risk factor management have been recently developed for healthcare providers delivering follow-up care to BCS and include maintaining a healthy weight, engaging in regular physical activity, adhering to a 1. Breast cancer management diet rich in fruits, vegetables and whole grains, reducing dietary fat consumption and limiting alcoholic intake [72]p. 1361.”

“Numerous studies have highlighted the value of hypnotic procedures in different clinical situations, such as stress or 2. Management in breast management, situations which are very frequent in cancer management [4]p. 115.”

“Generally speaking, the surgical management of the axilla in early breast cancer patients has evolved from Surgical management of 3. aggressive surgery towards less invasive surgery during the last two decades, and may even no surgery at all in some breast cancer selected patients with a low risk of ALN in the future. [73]p. 11.”

IX. DISCUSS RESEARCH

Fig. 6. A proposed framework that shows Breast cancer and its components

DOI: http://dx.doi.org/10.24018/ejers.2018.3.7.745 63 EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018

Fig. 7. A proposed framework that shows various factors of Breast cancer survive for 10 years, there will be an additional 1.1 SMs and their associated properties, function, composition and Mechanism of (excluding non-melanoma skin cancers). Approximately action 3.4% of SMs (excluding non-melanoma skin cancers) were X. RESULT AND FINDING attributable to RT. This is lower than previously published studies estimating that 5e9% of SMs were attributable to The most common risk factors among the registry RT. A prior SEER analysis of SMs in BC found organs participants were a strong family history of breast cancer estimated to receive _ 1 Gy during RT, including esophagus, and biopsy findings of a typia. Only one tenth of the pleura, lung, bone and soft tissues, had an increased relative population had BRCA1 or BRCA2 mutations. Quantifying risk of SMs. We found each of these high-risk organs to risk is a difficult endeavor; however, studies have shown have an increased risk of SMs in patients treated with RT that a strong family history can quadruple a woman’s risk of compared to those receiving surgery alone, with the breast cancer. a typia can increase a woman’s risk by 4- to exception of bone, joint and pleura malignancies. Despite 10-fold for AH and LCIS, respectively, and that BRCA1 or 3,644,524 person-years of follow-up, the O and E number of BRCA2 mutations can increase a woman’s risk of breast bone, joint and pleura. cancer 5- to 20-fold. The differences in risk factors between the 2 registries can be largely explained by the differences in XI. CONTRIBUTION AND NEW INTUITION enrollment practices between the 2 institutions. Knowledge and visibility of the registries to both medical and surgical Many contributions have been made regarding various disciplines is crucial for representative sampling factors that could lead to the development of breast cancer across risk factors. We found that while individual or which is one of the most lethal of the gynecologist cancer. women in either their primary childhood residential road or More need to be done regarding how these factors could cross street nearest to their primary childhood residence was eventually lead advance breast cancer disease so as to better divide by a barrier had a moderate increment in breast prevent, diagnose and treat it. This paper put together cancer risk. Combined analysis suggested a high exposure to different factors both genetics and environmental, their traffic-related pollutant and that is associated to the overall structure, function, composition, properties as well as the increment in breast cancer, post-menopausal breast cancer, mechanism at which they can cause ovarian cancer. Many of and invasive ER- breast cancer risk [40]. these factors are able to induce breast cancer development Among these options for premenopausal and metastasis by interrupting many important cellular patients with breast cancer, both endocrine therapy processes that plays a significant role in the biological (tamoxifen whether combined or not with ovarian system. Cellular processes such as cell cycle, DNA repair, suppression using GnRH agonists) and chemotherapy can Senescence and Apoptosis are deregulated and result in substantial bone loss from the suppression of inflammation, cell adhesion as well as breast cell transition oestrogen levels, premature menopause, or direct negative is also induced by some factors [74]-[79]. All of this in a effects of chemotherapy on bone [18]-[20]. Amenorrhea can way contributes to breast cancer development, its treatment, therefore result from ovarian function suppression or management and prevention. chemotherapy-induced ovarian failure. Chemotherapy- induced ovarian dysfunction accelerates the onset of XII. CONCLUSION menopause by an average of 10 years [21]. Between 25% The prognosis of breast cancer has improved due to the and 100% of premenopausal women may experience early comprehensive programmes and menopause or amenorrhea, especially in women over 40 development of new therapies. However, women with years of age [22]. Chemotherapy induced ovarian failure advanced or late breast cancer have a low 5-year survival results in substantial bone mineral density (BMD) loss of up rate. Generally, only 35% of women with late or advanced to 6–8% at the lumbar spine after 1 year [23],[24]. Ovarian breast cancer live for 5years after diagnosis. One third of function suppression with luteinizing hormone-releasing women with breast cancer are diagnosed at stage 4 when the hormone (LHRH) agonists such as goserelin leads to a mean cancer has poor diagnosis. Breast cancer treatment options 10.5% loss of BMD at the lumbar spine and 6.4% at the vary based on the stage at which the disease is diagnosed. femoral neck [25]. Tamoxifen alone and in combination Women diagnosed with early stage breast cancer are mostly with a LHRH agonist are standards of care for women with treated with radiotherapy or surgery while those with oestrogen receptor-positive breast cancer. Although advanced breast cancer are frequently treated with tamoxifen is a selective oestrogen receptor modulator with chemotherapy, hormonal and targeted therapies. some bone protective activity in postmenopausal women, it A better understanding of mechanism behind how some has also been associated with bone loss in premenopausal factors could induce the development of breast cancer cell patients. With an estimated 255,180 new cases of BC will aid in effectively devising strategies for the prevention predicted for 2017 and a 5-year OS rate near 90%treatment- and treatment of this cancer thus reducing its mortality and related toxicity is of particular concern in the management morbidity rate. of BC. Using a large population based database with long- term follow-up, this study found a significant excess risk of SMs in BC survivors compared to the general population. ACKNOWLEDGMENT However, only a small proportion of these cancers were I would like to thank Professor Bach. attributable to the use of post-operative RT. Overall, we found that for every 100 BC patients treated with RT who

DOI: http://dx.doi.org/10.24018/ejers.2018.3.7.745 64 EJERS, European Journal of Engineering Research and Science Vol. 3, No. 7, July 2018

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