Introduction

Introduction:
Breast cancer is an uncontrolled growth of breast cells. Breast cancer is reported to be the second most common type of cancer in the world and the most frequent cancer among women with an estimated of 1.67 million new cases diagnosed in 2012 (25% of all cancers)
International Agency for Cancer Research (IARC)/World Health Organisation (WHO) performed a project called GLOBOCAN 2012 and collected data from 184 countries, which show that breast cancer ranks as the fifth cause of death from cancer overall; it is the most frequent cause of cancer death in women in less developed countries and the second cause of cancer death in more developed regions, after lung cancer. ADDIN EN.CITE <EndNote><Cite><Author>Cancer</Author><Year>2012</Year><RecNum>58</RecNum><DisplayText>(Cancer, 2012; Organization, 2015)</DisplayText><record><rec-number>58</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1531168586″>58</key></foreign-keys><ref-type name=”Generic”>13</ref-type><contributors><authors><author>International Agency for Research on Cancer</author></authors></contributors><titles><title>GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012</title></titles><dates><year>2012</year></dates><urls></urls></record></Cite><Cite><Author>Organization</Author><Year>2015</Year><RecNum>59</RecNum><record><rec-number>59</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1531168660″>59</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>World Health Organization</author></authors></contributors><titles><title>GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012</title><secondary-title>Lung cancer fact sheet.Citated 2016 Jun 15. Available at http://globocan. iarc. fr/Pages/fact_sheets_cancer. aspx</secondary-title></titles><periodical><full-title>Lung cancer fact sheet.Citated 2016 Jun 15. Available at http://globocan. iarc. fr/Pages/fact_sheets_cancer. aspx</full-title></periodical><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>(Cancer, 2012; Organization, 2015)
Breast cancer is a complex and heterogeneous disease, comprising multiple tumor entities associated with distinctive histological patterns and different biological features and clinical behaviors. ADDIN EN.CITE <EndNote><Cite><Author>Weigelt</Author><Year>2009</Year><RecNum>16</RecNum><DisplayText>(Weigelt &amp; Reis-Filho, 2009)</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526942451″>16</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Weigelt, Britta</author><author>Reis-Filho, Jorge S.</author></authors></contributors><titles><title>Histological and molecular types of breast cancer: is there a unifying taxonomy?</title><secondary-title>Nature Reviews Clinical Oncology</secondary-title></titles><periodical><full-title>Nature reviews Clinical oncology</full-title></periodical><pages>718</pages><volume>6</volume><dates><year>2009</year><pub-dates><date>12/01/online</date></pub-dates></dates><publisher>Nature Publishing Group</publisher><work-type>Review Article</work-type><urls><related-urls><url>http://dx.doi.org/10.1038/nrclinonc.2009.166</url></related-urls></urls><electronic-resource-num>10.1038/nrclinonc.2009.166</electronic-resource-num></record></Cite></EndNote>(Weigelt & Reis-Filho, 2009)
Breast cancer is one of the important malignancies worldwide which has accounted as the most cancer among women. Early detection and monitoring of patients are found as main aspects of breast cancer therapy ADDIN EN.CITE <EndNote><Cite><Author>Weigel</Author><Year>2010</Year><RecNum>19</RecNum><DisplayText>(Weigel &amp; Dowsett, 2010)</DisplayText><record><rec-number>19</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526943162″>19</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Weigel, Marion T</author><author>Dowsett, Mitch</author></authors></contributors><titles><title>Current and emerging biomarkers in breast cancer: prognosis and prediction</title><secondary-title>Endocrine-related cancer</secondary-title></titles><periodical><full-title>Endocrine-related cancer</full-title></periodical><pages>R245-R262</pages><volume>17</volume><number>4</number><dates><year>2010</year></dates><isbn>1351-0088</isbn><urls></urls></record></Cite></EndNote>(Weigel & Dowsett, 2010) According to the World Health Organization (WHO, 2007), one million women have diagnosed annually with breast cancer in the world.
In Arab countries, breast cancer has the prevalence of being the most frequent cancer among women; it comprises between 14 to 42% ADDIN EN.CITE <EndNote><Cite><Author>Al-Sejari</Author><Year>2014</Year><RecNum>23</RecNum><DisplayText>(Al-Sejari &amp; Al-Kandari, 2014)</DisplayText><record><rec-number>23</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526944564″>23</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Al-Sejari, Maha M.</author><author>Al-Kandari, Yagoub Y.</author></authors></contributors><titles><title>Breast Cancer Knowledge and Awareness among Kuwaiti Women</title><secondary-title>Journal of the Gulf &amp; Arabian Peninsula Studies</secondary-title></titles><periodical><full-title>Journal of the Gulf &amp; Arabian Peninsula Studies</full-title></periodical><pages>17-45</pages><volume>40</volume><number>153</number><keywords><keyword>BREAST cancer risk factors</keyword><keyword>GENETIC disorders</keyword><keyword>DISEASES in women</keyword><keyword>CANCER diagnosis</keyword><keyword>KUWAIT</keyword></keywords><dates><year>2014</year></dates><publisher>Kuwait University, Academic Publication Council</publisher><isbn>02544288</isbn><accession-num>97064957</accession-num><work-type>Article</work-type><urls><related-urls><url>http://search.ebscohost.com/login.aspx?direct=true&amp;db=awr&amp;AN=97064957&amp;site=ehost-live</url></related-urls></urls><remote-database-name>awr</remote-database-name><remote-database-provider>EBSCOhost</remote-database-provider></record></Cite></EndNote>(Al-Sejari & Al-Kandari, 2014).
Globally, breast cancer is the most common cancer affecting women. In 2008 some 1,380,000 million new cases and 458,000 deaths were reported worldwide. One in eight women in the United States will be diagnosed with breast cancer. ADDIN EN.CITE <EndNote><Cite><Author>Tobias</Author><Year>2014</Year><RecNum>6</RecNum><DisplayText>(Tobias, Hochhauser, &amp; Tobias, 2014)</DisplayText><record><rec-number>6</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526846143″>6</key></foreign-keys><ref-type name=”Book”>6</ref-type><contributors><authors><author>Tobias, Jeffrey S</author><author>Hochhauser, Daniel</author><author>Tobias, Jeffrey</author></authors></contributors><titles><title>Cancer and its management</title></titles><dates><year>2014</year></dates><publisher>John Wiley &amp; Sons</publisher><isbn>1118468732</isbn><urls></urls></record></Cite></EndNote>(Tobias, Hochhauser, & Tobias, 2014)
About Breast Cancer:
Breast cancer is labeled according to where it arises, whether it is invasive and the appearance of the cells. Breast cancers can begin in glands called ducts (86%) or lobules (12%). These cancers are often referred to as adenocarcinomas. In rare cases, breast cancer can arise in the surrounding tissue. Cancer is also described as invasive (infiltrating) when it has spread into the surrounding tissue. Non-invasive carcinomas may be called ductal (or lobular) carcinoma in situ or intraductal carcinoma. Various names may be present in the pathology report, based on the appearance of the cells. ADDIN EN.CITE <EndNote><Cite><Author>Buchanan</Author><Year>2004</Year><RecNum>7</RecNum><DisplayText>(Buchanan, O&apos;connell, &amp; Mosconi, 2004)</DisplayText><record><rec-number>7</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526846574″>7</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Buchanan, Mary</author><author>O&apos;connell, Deirdre</author><author>Mosconi, Paola</author></authors></contributors><titles><title>EUROPA DONNA, the European breast cancer coalition: Lobbying at European and local levels</title><secondary-title>The Journal of ambulatory care management</secondary-title></titles><periodical><full-title>The Journal of ambulatory care management</full-title></periodical><pages>146-153</pages><volume>27</volume><number>2</number><dates><year>2004</year></dates><isbn>0148-9917</isbn><urls></urls></record></Cite></EndNote>(Buchanan, O’connell, ; Mosconi, 2004)
Types of Breast Cancer:
Subtypes are distinguished by patient characteristics or according to phenotypic or genotypic characteristics of the tumor such as tumor stage, grade, histological characteristics, genetic background, and clinical behaviors. Since subtypes also differ in their responses to clinical treatment, classification of breast cancers help in targeting treatment and improve therapy as well as prognostication.

Breast cancer cells taken out during a biopsy or surgery will be tested to see if they have certain proteins that are estrogen or progesterone receptors.

When the hormones estrogen and progesterone attach to these receptors, they fuel the cancer growth. Cancers are called hormone receptor-positive or hormone receptor-negative based on whether or not they have these receptors (proteins).

Normal breast cells and some breast cancer cells have receptors that attach to the hormones estrogen and progesterone, and depend on these hormones to grow.

Breast cancer cells may have one, both, or none of these receptors.

ER-positive: Breast cancers that have estrogen receptors are called ER-positive (or ER+) cancers.

PR-positive: Breast cancers with progesterone receptors are called PR-positive (or PR+) cancers.

Keeping these receptors from attaching to the hormones can help keep cancer from growing and spreading. There are drugs that can be used to do this. PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Tb3RpcmlvdTwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+
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ADDIN EN.CITE.DATA (Morrow M et al.; Sotiriou et al., 2006)
Classification of breast cancers has been suggested according to their gene expression patterns, tumors are divided into four subtypes depending on their Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression; luminal A, luminal B, triple negative basal-like and HER 2. ADDIN EN.CITE ;EndNote;;Cite;;Author;Phipps;/Author;;Year;2010;/Year;;RecNum;60;/RecNum;;DisplayText;(Perou et al., 2000; Phipps, Mirick, Li, ;amp; Davis, 2010);/DisplayText;;record;;rec-number;60;/rec-number;;foreign-keys;;key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1531169868″;60;/key;;/foreign-keys;;ref-type name=”Book Section”;5;/ref-type;;contributors;;authors;;author;Phipps, Amanda I;/author;;author;Mirick, Dana;/author;;author;Li, Christopher I;/author;;author;Davis, Scott;/author;;/authors;;/contributors;;titles;;title;Environmental and Occupational Exposures;/title;;secondary-title;Breast Cancer Epidemiology;/secondary-title;;/titles;;pages;183-221;/pages;;dates;;year;2010;/year;;/dates;;publisher;Springer;/publisher;;urls;;/urls;;/record;;/Cite;;Cite;;Author;Perou;/Author;;Year;2000;/Year;;RecNum;62;/RecNum;;record;;rec-number;62;/rec-number;;foreign-keys;;key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1531203199″;62;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Perou, Charles M;/author;;author;Sørlie, Therese;/author;;author;Eisen, Michael B;/author;;author;Van De Rijn, Matt;/author;;author;Jeffrey, Stefanie S;/author;;author;Rees, Christian A;/author;;author;Pollack, Jonathan R;/author;;author;Ross, Douglas T;/author;;author;Johnsen, Hilde;/author;;author;Akslen, Lars A;/author;;/authors;;/contributors;;titles;;title;Molecular portraits of human breast tumours;/title;;secondary-title;nature;/secondary-title;;/titles;;periodical;;full-title;Nature;/full-title;;/periodical;;pages;747;/pages;;volume;406;/volume;;number;6797;/number;;dates;;year;2000;/year;;/dates;;isbn;1476-4687;/isbn;;urls;;/urls;;/record;;/Cite;;/EndNote;(Perou et al., 2000; Phipps, Mirick, Li, ; Davis, 2010)
Luminal A type expresses ER and/or PR but do not express HER2. It is slow-growing and less aggressive than other subtypes. This type has the best prognosis among all subtypes with high survival and low recurrence rates. Expression of hormone receptors is suggested to be an explanation for this good prognosis since it is predictive of a favorable response to hormonal therapy.

Luminal B type tumors are ER(+) and/or PR(+), and differ from luminal A by expression of HER2. They have high proliferation rates and poorer prognosis compared to luminal A tumors.

Triple negative basal-like tumors are ER(-), PR(-), and HER2(-), as can be understood from its name.

They are aggressive and invasive tumors with the worst prognosis and unresponsiveness to conventional hormonal therapies.
HER2 type: do not express hormone receptors (neither ER nor PR) and tend to grow and spread more aggressively than other types.

Poorer short-term prognosis compared to luminal cancers but better than triple negative tumors as a result of the use of targeted therapies for HER2+ cancers ADDIN EN.CITE ;EndNote;;Cite;;Author;Reis-Filho;/Author;;Year;2011;/Year;;RecNum;63;/RecNum;;DisplayText;(Goldhirsch et al., 2011; Reis-Filho ;amp; Pusztai, 2011);/DisplayText;;record;;rec-number;63;/rec-number;;foreign-keys;;key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1531204956″;63;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Reis-Filho, Jorge S;/author;;author;Pusztai, Lajos;/author;;/authors;;/contributors;;titles;;title;Gene expression profiling in breast cancer: classification, prognostication, and prediction;/title;;secondary-title;The Lancet;/secondary-title;;/titles;;periodical;;full-title;The Lancet;/full-title;;/periodical;;pages;1812-1823;/pages;;volume;378;/volume;;number;9805;/number;;dates;;year;2011;/year;;/dates;;isbn;0140-6736;/isbn;;urls;;/urls;;/record;;/Cite;;Cite;;Author;Goldhirsch;/Author;;Year;2011;/Year;;RecNum;64;/RecNum;;record;;rec-number;64;/rec-number;;foreign-keys;;key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1531205292″;64;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Goldhirsch, A;/author;;author;Wood, William C;/author;;author;Coates, Alan S;/author;;author;Gelber, Richard D;/author;;author;Thürlimann, Beat;/author;;author;Senn, H-J;/author;;author;Panel Members;/author;;/authors;;/contributors;;titles;;title;Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011;/title;;secondary-title;Annals of oncology;/secondary-title;;/titles;;periodical;;full-title;Annals of oncology;/full-title;;/periodical;;pages;1736-1747;/pages;;volume;22;/volume;;number;8;/number;;dates;;year;2011;/year;;/dates;;isbn;0923-7534;/isbn;;urls;;/urls;;/record;;/Cite;;/EndNote;(Goldhirsch et al., 2011; Reis-Filho ; Pusztai, 2011)
In situ cancers: There are many types of breast cancer. The most common types are ductal carcinoma in situ, invasive ductal carcinoma, and invasive lobular carcinoma.. ADDIN EN.CITE ;EndNote;;Cite;;Author;Colditz;/Author;;Year;2007;/Year;;RecNum;10;/RecNum;;DisplayText;(Colditz, 2007);/DisplayText;;record;;rec-number;10;/rec-number;;foreign-keys;;key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526847067″;10;/key;;/foreign-keys;;ref-type name=”Book”;6;/ref-type;;contributors;;authors;;author;Colditz, Graham A;/author;;/authors;;/contributors;;titles;;title;Encyclopedia of cancer and society;/title;;/titles;;dates;;year;2007;/year;;/dates;;publisher;Sage Publications;/publisher;;isbn;1452265615;/isbn;;urls;;/urls;;/record;;/Cite;;/EndNote;(Colditz, 2007)
Ductal carcinoma in situ (DCIS; also known as intraductal carcinoma) is a non-invasive or pre-invasive breast cancer.

Lobular carcinoma in situ (LCIS) may also be called lobular neoplasia. This breast change is not cancer, though the name can be confusing. In LCIS, cells that look like cancer cells are growing in the lobules of the milk-producing glands of the breast, but they don’t grow through the wall of the lobules. ADDIN EN.CITE <EndNote><Cite><Author>Buchanan</Author><Year>2004</Year><RecNum>7</RecNum><DisplayText>(Buchanan et al., 2004)</DisplayText><record><rec-number>7</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526846574″>7</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Buchanan, Mary</author><author>O&apos;connell, Deirdre</author><author>Mosconi, Paola</author></authors></contributors><titles><title>EUROPA DONNA, the European breast cancer coalition: Lobbying at European and local levels</title><secondary-title>The Journal of ambulatory care management</secondary-title></titles><periodical><full-title>The Journal of ambulatory care management</full-title></periodical><pages>146-153</pages><volume>27</volume><number>2</number><dates><year>2004</year></dates><isbn>0148-9917</isbn><urls></urls></record></Cite></EndNote>(Buchanan et al., 2004)
Diagnosis Of Breast Cancer:
Ultrasounds are other major imaging techniques which are known as the most common method for diagnosis and monitoring response to therapy in breast cancer ADDIN EN.CITE <EndNote><Cite><Author>Ahmad</Author><Year>2011</Year><RecNum>20</RecNum><DisplayText>(Ahmad et al., 2011)</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526943567″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ahmad, Aamir</author><author>Aboukameel, Amro</author><author>Kong, Dejuan</author><author>Wang, Zhiwei</author><author>Sethi, Seema</author><author>Chen, Wei</author><author>Sarkar, Fazlul H</author><author>Raz, Avraham</author></authors></contributors><titles><title>Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells</title><secondary-title>Cancer research</secondary-title></titles><periodical><full-title>Cancer research</full-title></periodical><pages>3400-3409</pages><volume>71</volume><number>9</number><dates><year>2011</year></dates><isbn>0008-5472</isbn><urls></urls></record></Cite></EndNote>) .Ahmad et al., 2011(
Besides, mammography, using of ultrasound is required for the management and diagnosis of breast pathology ADDIN EN.CITE <EndNote><Cite><Author>Ozmen</Author><Year>2015</Year><RecNum>21</RecNum><DisplayText>(Ozmen et al., 2015)</DisplayText><record><rec-number>21</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526943753″>21</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ozmen, Neslihan</author><author>Dapp, Robin</author><author>Zapf, Michael</author><author>Gemmeke, Hartmut</author><author>Ruiter, Nicole V</author><author>van Dongen, Koen WA</author></authors></contributors><titles><title>Comparing different ultrasound imaging methods for breast cancer detection</title><secondary-title>IEEE transactions on ultrasonics, ferroelectrics, and frequency control</secondary-title></titles><periodical><full-title>IEEE transactions on ultrasonics, ferroelectrics, and frequency control</full-title></periodical><pages>637-646</pages><volume>62</volume><number>4</number><dates><year>2015</year></dates><isbn>0885-3010</isbn><urls></urls></record></Cite></EndNote>(Ozmen et al., 2015). MRI is found as other important diagnostic tools for breast cancer. This technique could be used for various aspects of breast cancer treatment including monitoring of response to therapy, assessment of breast cancer metastasis, and study of tumor recurrence ADDIN EN.CITE <EndNote><Cite><Author>Mann</Author><Year>2008</Year><RecNum>22</RecNum><DisplayText>(Mann, Kuhl, Kinkel, &amp; Boetes, 2008)</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1526943942″>22</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Mann, Ritse M</author><author>Kuhl, Christiane K</author><author>Kinkel, Karen</author><author>Boetes, Carla</author></authors></contributors><titles><title>Breast MRI: guidelines from the European society of breast imaging</title><secondary-title>European radiology</secondary-title></titles><periodical><full-title>European radiology</full-title></periodical><pages>1307-1318</pages><volume>18</volume><number>7</number><dates><year>2008</year></dates><isbn>0938-7994</isbn><urls></urls></record></Cite></EndNote>(Mann, Kuhl, Kinkel, & Boetes, 2008)
What are the Risks for Breast Cancer?
The possible risk factors for breast cancer have been reported as:
1.Increasing age
2. Long time exposure to estrogen via
-early menarche (< 12)
-late menopause (>55)
-late age at first birth (?30)
-having no children
-oral contraceptives
-hormone replacement therapy
3.Family history
4. Personal history of breast cancer
5. Previously diagnosed benign breast disease
6. Dense breasts
7. Radiation therapy
8. Diet and lifestyle (obesity
, alcohol consumption, smoking, not excersicing etc) ADDIN EN.CITE <EndNote><Cite><Author>Gurer-Orhan</Author><Year>2017</Year><RecNum>65</RecNum><DisplayText>(Gurer-Orhan, Ince, Suzen, &amp; Saso, 2017)</DisplayText><record><rec-number>65</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1531205452″>65</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Gurer-Orhan, Hande</author><author>Ince, Elif</author><author>Suzen, Sibel</author><author>Saso, Luciano</author></authors></contributors><titles><title>The Role Of Oxidative Stress Modulators In Breast Cancer</title><secondary-title>inflammation</secondary-title></titles><periodical><full-title>inflammation</full-title></periodical><pages>15</pages><volume>14</volume><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>(Gurer-Orhan, Ince, Suzen, & Saso, 2017)
Symptoms of breast cancer: Initially, breast cancer may not cause any symptoms. Signs and symptoms often appear when the tumor grows large enough to be felt as a lump in the breast or when the cancer spreads to surrounding tissues and organs, any of the following unusual changes in the breast can be a symptom of breast cancer:
swelling of all or part of the breast
skin irritation or dimpling
breast pain
nipple pain or the nipple turning inward
redness, scaliness, or thickening of the nipple or breast skin
a nipple discharge other than breast milk
a lump in the underarm area

Late signs and symptoms occur as cancer grows larger or spreads to other parts of the body, including other organs. Late symptoms of breast cancer include:
bone pain
weight loss
nausea
loss of appetite
jaundiceshortness of breath
cough
headache
double vision
muscle weakness ADDIN EN.CITE <EndNote><Cite><Author>Molckovsky</Author><Year>2009</Year><RecNum>27</RecNum><DisplayText>(Molckovsky, Fitzgerald, Freedman, Heisey, &amp; Clemons, 2009)</DisplayText><record><rec-number>27</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1527175766″>27</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Molckovsky, Andrea</author><author>Fitzgerald, Barbara</author><author>Freedman, Orit</author><author>Heisey, Ruth</author><author>Clemons, Mark</author></authors></contributors><titles><title>Approach to inflammatory breast cancer</title><secondary-title>Canadian Family Physician</secondary-title></titles><periodical><full-title>Canadian Family Physician</full-title></periodical><pages>25-31</pages><volume>55</volume><number>1</number><dates><year>2009</year></dates><isbn>0008-350X</isbn><urls></urls></record></Cite></EndNote>(Molckovsky, Fitzgerald, Freedman, Heisey, & Clemons, 2009)
CLUSTER OF DIFRRENTIATION:
The cluster of differentiation (CD) designation refers to cell surface proteins. Each unique molecule is assigned a different number designation, which allows identification of cell phenotypes. Surface expression of a particular CD molecule may not be specific for just one cell or even a cell lineage; however, many are useful for characterization of cell phenotypes. The official listing of determinants has identified over 350 individual and unique markers. ADDIN EN.CITE <EndNote><Cite><Author>Actor</Author><Year>2014</Year><RecNum>30</RecNum><DisplayText>(Actor, 2014)</DisplayText><record><rec-number>30</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530284247″>30</key></foreign-keys><ref-type name=”Book”>6</ref-type><contributors><authors><author>Actor, Jeffrey K</author></authors></contributors><titles><title>Introductory Immunology: Basic Concepts for Interdisciplinary Applications</title></titles><dates><year>2014</year></dates><publisher>Academic Press</publisher><isbn>0124200729</isbn><urls></urls></record></Cite></EndNote>(Actor, 2014)
CD (cluster of differentiation) are cell surface molecules expressed on leukocytes and other cells relevant to the immune system. CD markers are used to classify white blood cells produced by the body to help fight infection. These cells are central components of the immune system which work in tandem to identify, target, and neutralize disease-causing pathogens.

CD molecules are commonly used as cell markers, allowing the identification and isolation of leukocyte populations, subsets, and differentiation stage ADDIN EN.CITE <EndNote><Cite><Author>Zola</Author><Year>2005</Year><RecNum>29</RecNum><DisplayText>(Zola et al., 2005)</DisplayText><record><rec-number>29</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530284008″>29</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Zola, Heddy</author><author>Swart, Bernadette</author><author>Nicholson, Ian</author><author>Aasted, Bent</author><author>Bensussan, Armand</author><author>Boumsell, Laurence</author><author>Buckley, Chris</author><author>Clark, Georgina</author><author>Drbal, Karel</author><author>Engel, Pablo</author></authors></contributors><titles><title>CD molecules 2005: human cell differentiation molecules</title><secondary-title>Blood</secondary-title></titles><periodical><full-title>Blood</full-title></periodical><pages>3123-3126</pages><volume>106</volume><number>9</number><dates><year>2005</year></dates><isbn>0006-4971</isbn><urls></urls></record></Cite></EndNote>(Zola et al., 2005)
CD Markers in Cancer Diagnosis and Treatment:
In addition to monitoring infection and immune status, CD antigens can be used to detect the abnormal growth of cells known as a neoplasm.
CD markers are not only important in the diagnosis of cancer, but they can also help identify which types of treatment may be most successful and measure how effective the treatment is by monitoring changes in the relevant CD markers. ADDIN EN.CITE <EndNote><Cite><Author>Clarke</Author><Year>2009</Year><RecNum>31</RecNum><DisplayText>(Clarke et al., 2009)</DisplayText><record><rec-number>31</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530284878″>31</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Clarke, Robert</author><author>Peden, John F</author><author>Hopewell, Jemma C</author><author>Kyriakou, Theodosios</author><author>Goel, Anuj</author><author>Heath, Simon C</author><author>Parish, Sarah</author><author>Barlera, Simona</author><author>Franzosi, Maria Grazia</author><author>Rust, Stephan</author></authors></contributors><titles><title>Genetic variants associated with Lp (a) lipoprotein level and coronary disease</title><secondary-title>New England Journal of Medicine</secondary-title></titles><periodical><full-title>New England Journal of Medicine</full-title></periodical><pages>2518-2528</pages><volume>361</volume><number>26</number><dates><year>2009</year></dates><isbn>0028-4793</isbn><urls></urls></record></Cite></EndNote>(Clarke et al., 2009)
CD20: CD20 is a 33- to 37-kDa, non-glycosylated phosphoprotein, a membrane-embedded surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. CD20 is expressed in a vast majority of mature B-cell neoplasms and some cases of B-lymphoblastic leukemia/lymphomas, plasma cell myelomas, Hodgkin lymphomas, T-cell neoplasms, and AMLs. ADDIN EN.CITE <EndNote><Cite><Author>Naeim</Author><Year>2012</Year><RecNum>41</RecNum><DisplayText>(Naeim, 2012)</DisplayText><record><rec-number>41</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530452060″>41</key></foreign-keys><ref-type name=”Book”>6</ref-type><contributors><authors><author>Naeim, Faramarz</author></authors></contributors><titles><title>Atlas of hematopathology: morphology, immunophenotype, cytogenetics, and molecular approaches</title></titles><dates><year>2012</year></dates><publisher>Academic Press</publisher><isbn>012385184X</isbn><urls></urls></record></Cite></EndNote>(Naeim, 2012)
PDL1:
PD-1 is a type 1 transmembrane protein that encoded by the PDCD1 gene , PD-L1 is expressed on a variety of cell types, including placenta, vascular endothelium, pancreatic islet cells, muscle, hepatocytes, epithelium, and mesenchymal stem cells, as well as on B cells, T cells, dendritic cells, macrophages, and mast cells ADDIN EN.CITE <EndNote><Cite><Author>Sharpe</Author><Year>2007</Year><RecNum>40</RecNum><DisplayText>(Sharpe, Wherry, Ahmed, &amp; Freeman, 2007)</DisplayText><record><rec-number>40</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530356846″>40</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Sharpe, Arlene H</author><author>Wherry, E John</author><author>Ahmed, Rafi</author><author>Freeman, Gordon J</author></authors></contributors><titles><title>The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection</title><secondary-title>Nature immunology</secondary-title></titles><periodical><full-title>Nature immunology</full-title></periodical><pages>239</pages><volume>8</volume><number>3</number><dates><year>2007</year></dates><isbn>1529-2916</isbn><urls></urls></record></Cite></EndNote>(Sharpe, Wherry, Ahmed, & Freeman, 2007)
Programmed death ligand 1 (PDL1) is highly expressed on the surface of a variety of cancer cells. It is well known that PDL1 inhibits the proliferation and function of tumor-infiltrating lymphocytes (TILs), leading to an immunosuppressive environment in cancers. ADDIN EN.CITE <EndNote><Cite><Author>Dong</Author><Year>2002</Year><RecNum>28</RecNum><DisplayText>(Dong et al., 2002)</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530280881″>28</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Dong, Haidong</author><author>Strome, Scott E</author><author>Salomao, Diva R</author><author>Tamura, Hideto</author><author>Hirano, Fumiya</author><author>Flies, Dallas B</author><author>Roche, Patrick C</author><author>Lu, Jun</author><author>Zhu, Gefeng</author><author>Tamada, Koji</author></authors></contributors><titles><title>Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion</title><secondary-title>Nature medicine</secondary-title></titles><periodical><full-title>Nature medicine</full-title></periodical><pages>793</pages><volume>8</volume><number>8</number><dates><year>2002</year></dates><isbn>1546-170X</isbn><urls></urls></record></Cite></EndNote>(Dong et al., 2002) PD-L1 is expressed on breast cancer cells. ADDIN EN.CITE <EndNote><Cite><Author>Ghebeh</Author><Year>2006</Year><RecNum>37</RecNum><DisplayText>(Ghebeh et al., 2006)</DisplayText><record><rec-number>37</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530300471″>37</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Ghebeh, Hazem</author><author>Mohammed, Shamayel</author><author>Al-Omair, Abeer</author><author>Qattant, Amal</author><author>Lehe, Cynthia</author><author>Al-Qudaihi, Ghofran</author><author>Elkum, Naser</author><author>Alshabanah, Mohamed</author><author>Amer, Suad Bin</author><author>Tulbah, Asma</author></authors></contributors><titles><title>The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors</title><secondary-title>Neoplasia</secondary-title></titles><periodical><full-title>Neoplasia</full-title></periodical><pages>190-198</pages><volume>8</volume><number>3</number><dates><year>2006</year></dates><isbn>1476-5586</isbn><urls></urls></record></Cite></EndNote>(Ghebeh et al., 2006)
.

Flow Cytometry: Flow cytometry is an optical, laser-based technology which analyzes the physical and fluorescent properties of cells in suspension in real-time as they flow through the instrument.

Flow cytometry is the technique where these measurements are made individually of single particles (cells, nuclei, chromosomes), suspended within a stream of liquid, as they pass through a laser light source. The light scatter and emitted fluorescence of each particle is collected, filtered and converted to digital values which are stored on a computer. ADDIN EN.CITE <EndNote><Cite><Author>Patel</Author><Year>2008</Year><RecNum>46</RecNum><DisplayText>(H. R. Patel, Arya, &amp; Shergill, 2008)</DisplayText><record><rec-number>46</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530890820″>46</key></foreign-keys><ref-type name=”Book”>6</ref-type><contributors><authors><author>Patel, Hitendra RH</author><author>Arya, Manit</author><author>Shergill, Iqbal</author></authors></contributors><titles><title>Basic science techniques in clinical practice</title></titles><dates><year>2008</year></dates><publisher>Springer Science &amp; Business Media</publisher><isbn>1846287405</isbn><urls></urls></record></Cite></EndNote>(H. R. Patel, Arya, & Shergill, 2008)
There are many applications of flow cytometry in both basic and clinical research. The technology permits rapid and accurate measurements of multiple cell and intracellular characteristics that include DNA/RNA cell content, mitochondria and chromosomes, enzyme activity, membrane potential, the measurement of intracellular pH or ions such as calcium, the detection and quantification of cell antigens, the analysis of multidrug resistance. ADDIN EN.CITE <EndNote><Cite><Author>Fleisher</Author><Year>2005</Year><RecNum>47</RecNum><DisplayText>(Fleisher &amp; Braylan, 2005; Herzenberg et al., 2002)</DisplayText><record><rec-number>47</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530892401″>47</key></foreign-keys><ref-type name=”Book Section”>5</ref-type><contributors><authors><author>Fleisher, Thomas A</author><author>Braylan, Raul C</author></authors></contributors><titles><title>Basic principles and clinical applications of flow cytometry</title><secondary-title>Bethesda handbook of clinical hematology</secondary-title></titles><pages>415-424</pages><dates><year>2005</year></dates><publisher>Lippincott Williams &amp; Wilkins, Baltimore</publisher><urls></urls></record></Cite><Cite><Author>Herzenberg</Author><Year>2002</Year><RecNum>48</RecNum><record><rec-number>48</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530892520″>48</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Herzenberg, Leonard A</author><author>Parks, David</author><author>Sahaf, Bita</author><author>Perez, Omar</author><author>Roederer, Mario</author><author>Herzenberg, Leonore A</author></authors></contributors><titles><title>The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford</title><secondary-title>Clinical chemistry</secondary-title></titles><periodical><full-title>Clinical chemistry</full-title></periodical><pages>1819-1827</pages><volume>48</volume><number>10</number><dates><year>2002</year></dates><isbn>0009-9147</isbn><urls></urls></record></Cite></EndNote>(Fleisher & Braylan, 2005; Herzenberg et al., 2002)
Immuno-histochemistry: (IHC) Immunohistochemistry describes the localization of antigens in histological and cytological preparations using antibodies. Immunohistochemistry can be performed on cytological preparations, frozen sections, and paraffin-embedded histological sections. ADDIN EN.CITE <EndNote><Cite><Author>Shi</Author><Year>1991</Year><RecNum>42</RecNum><DisplayText>(Shi, Key, &amp; Kalra, 1991)</DisplayText><record><rec-number>42</rec-number><foreign-keys><key app=”EN” db-id=”daaaafze7pd2f8ead2a5eatwap59d0afwsrs” timestamp=”1530889446″>42</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Shi, Shan-Rong</author><author>Key, MARC E</author><author>Kalra, KRISHAN L</author></authors></contributors><titles><title>Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections</title><secondary-title>Journal of Histochemistry &amp; Cytochemistry</secondary-title></titles><periodical><full-title>Journal of Histochemistry &amp; Cytochemistry</full-title></periodical><pages>741-748</pages><volume>39</volume><number>6</number><dates><year>1991</year></dates><isbn>0022-1554</isbn><urls></urls></record></Cite></EndNote>(Shi, Key, & Kalra, 1991)
Aim of the work:
1-To investigate new markers for early diagnosis of breast cancer.2-To compare between levels of some biomarkers in blood and tissues samples of patients with breast cancer.References:
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