Breast cancer 70547 225981415 2008-07-16T09:05:29Z THEN WHO WAS PHONE? 7456377 Reverted 7 edits by [[Special:Contributions/12.168.59.4|12.168.59.4]] identified as [[WP:VAND|vandalism]] to last revision by [[User:Sfmammamia|Sfmammamia]]. ([[WP:TW|TW]]) {{Infobox_Disease | Name = Breast Cancer | Image = Mammogram showing breast cancer.jpg | Caption = Mammogram showing breast cancer (indicated by arrow)| DiseasesDB = 1598 | ICD10 = {{ICD10|C|50||c|50}} | ICD9 = {{ICD9|174}}-{{ICD9|175}} | ICDO = | OMIM = 114480 | MedlinePlus = 000913 | eMedicineSubj = med | eMedicineTopic = 2808 | MeshID = D001943 | }} '''Breast cancer''' is a [[cancer]] that starts in the [[Cell (biology)|cells]] of the [[breast]] in men and women.<ref name="acs what is bc">{{cite web |author=[[American Cancer Society]] |month=September 26, |year=2007 |title=What Is Breast Cancer? |url=http://www.cancer.org/docroot/CRI/content/CRI_2_2_1X_What_is_breast_cancer_5.asp?sitearea= |accessdate=2008-02-03}}</ref> Worldwide, breast cancer is the second most common type of cancer after [[lung cancer]] (10.4% of all cancer incidence, both sexes counted)<ref name="WHO WCR">{{cite web |author=[[World Health Organization]] [[International Agency for Research on Cancer]] |month=June |year=2003 |title=World Cancer Report |url=http://www.iarc.fr/IARCPress/pdfs/wcr/index.php |accessdate=2008-02-03}}</ref> and the fifth most common cause of cancer death.<ref name="who fact sheet">{{cite web |author=World Health Organization |month=February |year=2006 |title=Fact sheet No. 297: Cancer |url=http://www.who.int/mediacentre/factsheets/fs297/en/index.html |accessdate=2007-04-26}}</ref> Worldwide, breast cancer is by far the most common cancer amongst women, with an incidence rate more than twice that of colorectal cancer and cervical cancer and about three times that of lung cancer. However breast cancer mortality worldwide is just 25% greater than that of lung cancer in women.<ref name="WHO WCR"/> In 2005, breast cancer caused 502,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths).<ref name="who fact sheet"/> The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.<ref name=indy>{{cite news | last = Laurance | first = Jeremy | title = Breast cancer cases rise 80% since Seventies | work = [[The Independent]] |date=2006-09-29 | url = http://www.independent.co.uk/life-style/health-and-wellbeing/health-news/breast-cancer-cases-rise-80-since-seventies-417990.html | accessdate = 2006-10-09 }}</ref><ref>{{cite web | title = Breast Cancer: Statistics on Incidence, Survival, and Screening | work = [http://imaginis.com/ Imaginis Corporation] |date=2006 | url = http://imaginis.com/breasthealth/statistics.asp | accessdate = 2006-10-09 }}</ref> The incidence of breast cancer varies greatly around the world, being lower in less-developed countries and greatest in the more-developed countries. In the twelve world regions, the annual age-standardized incidence rates per 100,000 women are as follows: in Eastern Asia, 18; South Central Asia, 22; sub-Saharan Africa, 22; South-Eastern Asia, 26; North Africa and Western Asia, 28; South and Central America, 42; Eastern Europe, 49; Southern Europe, 56; Northern Europe, 73; Oceania, 74; Western Europe, 78; and in North America, 90.<ref>[http://www.scribd.com/doc/2350813/World-Cancer-Report-2003-Stuart-e-Kleihues-WHO-e-IARC Stewart B. W. and Kleihues P. (Eds): World Cancer Report. IARCPress. Lyon 2003]</ref> Women in the United States have the highest incidence rates of breast cancer in the world; 141 among white women and 122 among African American women.<ref>Ries LAG, Eisner MP, Kosary CL, et al. SEER Cancer Statistics Review, 1975–2000. Bethesda, MD: National Cancer Institute, 2003.</ref><ref name="acs bc key stats"/> Among women in the US, breast cancer is the most common cancer and the second-most common cause of cancer death (after lung cancer).<ref name="acs bc key stats">{{cite web |author=American Cancer Society |month=September 13, |year=2007 |title=What Are the Key Statistics for Breast Cancer?|url=http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_breast_cancer_5.asp |accessdate=2008-02-03}}</ref> Women in the US have a 1 in 8 (12.5%) lifetime chance of developing invasive breast cancer and a 1 in 35 (3%) chance of breast cancer causing their death.<ref name="acs bc key stats"/> In 2007, breast cancer was expected to cause 40,910 deaths in the US (7% of cancer deaths; almost 2% of all deaths).<ref name="acs cancer facts 2007">{{cite web |author=American Cancer Society |year=2007 |title=Cancer Facts & Figures 2007 |url=http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf |accessdate=2007-04-26}}</ref> In the US, both incidence and death rates for breast cancer have been declining in the last few years.<ref name="pmid17939129">{{cite journal |author=Espey DK, Wu XC, Swan J, ''et al'' |title=Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska Natives |journal=Cancer |volume=110 |issue=10 |pages=2119–52 |year=2007 |pmid=17939129 |doi=10.1002/cncr.23044}}</ref><ref name="acs cancer facts 2007"/> Nevertheless, a US study conducted in 2005 by the [[Society for Women's Health Research]] indicated that breast cancer remains the most feared disease,<ref>{{cite press release |title=Women's Fear of Heart Disease Has Almost Doubled in Three Years, But Breast Cancer Remains Most Feared Disease | publisher=Society for Women's Health Research |date=2005-07-07 | url=http://www.womenshealthresearch.org/site/News2?page=NewsArticle&id=5459&news_iv_ctrl=0&abbr=press_ |accessdate=2007-10-15 }} </ref> even though [[heart disease]] is a much more common cause of death among women.<ref>{{cite web |url=http://www.nhlbi.nih.gov/health/hearttruth/press/infograph_dressgraph.pdf |title=Leading Causes of Death for American Women 2004 |accessdate=2007-10-15 |format=PDF |work=National Heart Lung and Blood Institute }}</ref> Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males.<ref name=Dave>{{cite web | title = Male Breast Cancer Treatment - National Cancer Institute | work = [http://www.cancer.gov/ National Cancer Institute] |date=2006 | url = http://www.cancer.gov/cancertopics/pdq/treatment/malebreast/healthprofessional | accessdate = 2006-10-16 }}</ref><ref>{{cite web | title = Breast Cancer in Men: Cancer Research UK | work = [http://www.cancerhelp.org.uk/ Cancer Research UK] |date=2007 | url = http://www.cancerhelp.org.uk/help/default.asp?page=5075 | accessdate = 2007-11-06 }}</ref> Incidences of breast cancer in men are approximately 100 times less common than in women, but men with breast cancer are considered to have the same statistical survival rates as women.<ref name="acs bc key stats men">{{cite web |author=American Cancer Society |month=September 27, |year=2007 |title=What Are the Key Statistics About Breast Cancer in Men? |url=http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_male_breast_cancer_28.asp?sitearea= |accessdate=2008-02-03}}</ref> ==Classification== {{splitsection}} <!-- [[Image:BCtimeline.jpg|thumb|450px|Time line of breast cancer suggesting probable [[heterogeneity]]. Primary breast cancers begin as single (or more) cells which have lost normal regulation of differentiation and proliferation but remain confined within the [[basement membrane]] of the [[duct]] or [[lobule]]. As these cells go through several doublings, at some point they invade through the basement membrane of the duct or lobule and ultimately [[metastasize]] to distant organs.<ref>Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics (Contemporary Cancer Research) by Anne M. Bowcock (1999)</ref>]] image is deleted --> Breast cancers are described along four different classification schemes, or groups, each based on different criteria and serving a different purpose: *[[Pathology]] - A [[surgical pathology|pathologist]] will categorize each tumor based on its [[Histology|histological]] (microscopic anatomy) appearance and other criteria. The most common pathologic types of breast cancer are invasive [[ductal carcinoma]], [[malignant]] cancer in the breast's [[Duct (anatomy)|ducts]], and invasive [[lobular carcinoma]], malignant cancer in the breast's [[Lobe (anatomy)|lobules]]. *[[Bloom-Richardson grade|Grade of tumor]] - The histological grade of a [[tumor]] is determined by a pathologist under a microscope. A ''well-differentiated'' (low grade) tumor resembles normal tissue. A ''poorly differentiated'' (high grade) tumor is composed of disorganized cells and, therefore, does not look like normal tissue. ''Moderately differentiated'' (intermediate grade) tumors are somewhere in between. *[[Protein expression|Protein]] & [[gene expression]] status - Currently, all breast cancers should be tested for expression, or detectable effect, of the [[estrogen receptor]] (ER), [[progesterone receptor]] (PR) and [[HER2/neu]] proteins. These tests are usually done by [[immunohistochemistry]] and are presented in a pathologist's report. The profile of expression of a given tumor helps predict its [[prognosis]], or outlook, and helps an [[oncology|oncologist]] choose the most appropriate treatment. More genes and/or proteins may be tested in the future. *Stage of a tumor - The currently accepted staging scheme for breast cancer is the [[TNM classification]]. There are five tumor classification values (Tis, T1, T2, T3 or T4) which depend on the presence or absence of invasive cancer, the dimensions of the invasive cancer, and the presence or absence of invasion outside of the breast (e.g. to the skin of the breast, to the muscle or to the rib cage underneath): *Tx - Primary tumor cannot be assessed. *T0 - No evidence of primary tumor. *Tis - Carcinoma in situ. ** Tis([[Ductal carcinoma|DCIS]]) - Intraductal Carcinoma in situ. ** Tis([[LCIS]]) - Lobular Carcinoma in situ. ** Tis(Paget's) - [[Paget's disease of the breast|Paget's disease]] of the nipple with no tumor. * T1 - Tumor 2cm or less in its greatest dimension. ** T1mic - Microinvasion 0.1cm or less in greatest dimension. ** T1a - Tumor more then 0.1cm but not more than 0.5cm in its greatest dimension. ** T1b - Tumor more than 0.5cm but not more than 1.0cm in its greatest dimension. ** T1c - Tumor more than 1.0cm but not more than 2.0cm in its greatest dimension. *T2 - Tumor more than 2.0cm but not more than 5.0cm in its greatest dimension. *T3 - Tumor more than 5cm in its greatest dimension. *T4 - Tumor of any size with direct extension to (a) chest wall or (b) skin as described below: ** T4a - Extension to chest wall. ** T4b - [[Edema]] (including [[peau d'orange]]) or ulceration of the breast skin, or satellite skin nodules confined to the same breast. ** T4c - Both T4a and T4b. ** T4d - [[Inflammatory breast cancer]]. [[lymph node|Lymph '''N'''ode]] - There are four lymph node classification values (N0, N1, N2 or N3) which depend on the number, size and location of breast cancer cell deposits in lymph nodes. * Nx - regional lymph nodes cannot be assessed. Perhaps due to previous removal. * N0 - no regional lymph node metastasis. * N1 - metastasis to movable regional axillary lymph nodes on the same side as the affected breast. * N2 - metastasis to fixed regional axillary lymph nodes, or metastasis to the internal mammary lymph nodes, on the same side as the affected breast. * N3 - metastasis to supraclavicular lymph nodes or infraclavicular lymph nodes or metastasis to the internal mammary lymph nodes with metastasis to the axillary lymph nodes. [[Metastasis|'''M'''etastases]] - There are two metastatic classification values (M0 or M1) which depend on the presence or absence of breast cancer cells in locations other than the breast and lymph nodes (so-called distant metastases, e.g. to bone, brain, lung). ===Pathologic types=== '''Note: The following table includes benign tumours (non cancers) as well as malignant tumours (cancers)''' The latest (2003) [[World Health Organization]] (WHO) classification of tumors of the breast<ref>''Tumours of the breast and female genital organs'', WHO classification of tumours, 2003, ISBN 92 832 2412 4</ref> recommends the following pathological types: {{col-begin}} {{col-break}} '''Invasive breast carcinomas''' * [[Ductal carcinoma|Invasive ductal carcinoma]] ** Most are "not otherwise specified" ** The remainder are given subtypes: *** Mixed type carcinoma *** Pleomorphic carcinoma *** Carcinoma with osteoclastic giant cells *** Carcinoma with choriocarcinomatous features *** Carcinoma with melanotic features * Invasive lobular carcinoma * Tubular carcinoma * Invasive cribriform carcinoma * Medullary carcinoma * Mucinous carcinoma and other tumours with abundant mucin ** Mucinous carcinoma ** Cystadenocarcinoma and columnar cell mucinous carcinoma ** [[Signet ring cell carcinoma]] * [[Neuroendocrine]] tumours ** Solid neuroendocrine carcinoma ([[carcinoid]] of the breast) ** Atypical carcinoid tumour ** Small cell / [[oat cell carcinoma]] ** Large cell neuroendocrine carcioma * Invasive papillary carcinoma * Invasive micropapillary carcinoma * Apocrine carcinoma * Metaplastic carcinomas ** Pure epithelial metaplastic carciomas *** [[Squamous cell carcinoma]] *** Adenocarcinoma with spindle cell metaplasia *** Adenosquamous carcinoma *** [[Mucoepidermoid carcinoma]] ** Mixed epithelial/mesenchymal metaplastic carcinomas * Lipid-rich carcinoma * Secretory carcinoma * Oncocytic carcinoma * Adenoid cystic carcinoma * Acinic cell carcinoma * Glycogen-rich clear cell carcinoma * Sebaceous carcinoma * [[Inflammatory breast cancer|Inflammatory carcinoma]] * Bilateral breast carcinoma '''Mesenchymal tumors''' (including [[sarcoma]]) * Haemangioma * Angiomatosis * Haemangiopericytoma * Pseudoangiomatous stromal hyperplasia * Myofibroblastoma * Fibromatosis (aggressive) * Inflammatory myofibroblastic tumour * [[Lipoma]] ** Angiolipoma * Granular cell tumour * [[Neurofibroma]] * [[Schwannoma]] * Angiosarcoma * Liposarcoma * Rhabdomyosarcoma * Osteosarcoma * [[Leiomyoma]] * Leiomysarcoma {{col-break}} '''Precursor lesions''' * Lobular neoplasia ** lobular carcinoma in situ * Intraductal proliferative lesions ** Usual ductal [[hyperplasia]] ** Flat epithelial hyperplasia ** Atypical ductal hyperplasia ** [[Ductal carcinoma in situ]] * Microinvasive carcinoma * Intraductal papillary neoplasms ** Central [[papilloma]] ** Peripheral papilloma ** Atypical papilloma ** Intraductal papillary carcinoma ** Intracystic papillary carcinoma '''Benign epithelial lesions''' * Adenosis, includin variants ** Sclerosing adenosis ** Apocrine adenosis ** Blunt duct adenosis ** Microglandular adenosis ** Adenomyoepithelial adenosis * Radial scar / complex sclerosing lesion * Adenomas ** Tubular adenoma ** Lactating adenoma ** Apocrine adenoma ** [[Pleomorphic adenoma]] ** Ductal adenoma '''Myoepithelial lesions''' * Myoepitheliosis * Adenomyoepithelial adenosis * Adenomyoepithelioma * Malignant myoepithelioma '''Fibroepithelial tumours''' * [[Fibroadenoma]] * [[Phyllodes tumour]] ** Benign ** Borderline ** Malignant * Periductal stromal sarcoma, low grade * Mammary [[hamartoma]] '''Tumours of the nipple''' * Nipple adenoma * Syringomatous adenoma * [[Paget's disease]] of the nipple '''Malignant [[lymphoma]]''' '''Metastatic tumours''' '''Tumours of the male breast''' * [[Gynecomastia]] * Carcinoma ** In situ ** Invasive {{col-end}} The classifications above show that breast cancer is usually, but not always, classified by its histological appearance. Rare variants are defined on the basis of [[physical exam]] findings. For example, [[Inflammatory breast cancer]] (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other [[carcinoma]]s by the [[inflammation|inflamed]] appearance of the affected breast.<ref>{{cite journal |author=Giordano SH, Hortobagyi GN |title=Inflammatory breast cancer: clinical progress and the main problems that must be addressed |journal=Breast Cancer Res. |volume=5 |issue=6 |pages=284–8 |year=2003 |pmid=14580242 |doi=10.1186/bcr608}} [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14580242 Free Full Text].</ref> In the future, some pathologic classifications may be changed. For example, a subset of ductal carcinomas may be re-named [[basal-like carcinoma]] (part of the [[Triple Negative Breast Cancer|"triple-negative" tumors]]).{{Fact|date=February 2008}} ==Signs and symptoms== The first [[symptom]], or subjective sign, of breast cancer is typically a lump that feels different than the surrounding breast tissue. According to the [[Merck Manual of Diagnosis and Therapy|Merck Manual]], greater than 80% of breast cancer cases are discovered as a lump by the woman herself.<ref name="merck">{{cite web |author=[[Merck Manual of Diagnosis and Therapy]] |month=February |year=2003 |title=Breast Disorders: Cancer |url=http://www.merck.com/mmhe/sec22/ch251/ch251f.html#sec22-ch251-ch251f-525 |accessdate=2008-02-05}}</ref> According to the [[American Cancer Society]] (ACS), the first [[medical sign]], or objective indication of breast cancer as detected by a physician, is discovered by mammogram.<ref name="acs cancer facts 2007"/> Lumps found in lymph nodes located in the armpits<ref name="merck"/> and/or collarbone{{Fact|date=February 2008}} can also indicate breast cancer. Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain is an unreliable tool in determining the presence of breast cancer, but may be indicative of other [[Breast health|breast-related health]] issues such as [[mastodynia]].<ref name="acs cancer facts 2007"/><ref name="merck"/><ref name="eMed">{{cite web |author=[[eMedicine]] |month=August 23, |year=2006 |title=Breast Cancer Evaluation |url=http://www.emedicine.com/med/TOPIC3287.HTM |accessdate=2008-02-05}}</ref> When breast cancer cells invade the dermal lymphatics, small lymph vessels in the skin of the breast, its presentation can resemble skin inflammation and thus is known as inflammatory breast cancer (IBC). Symptoms of inflammatory breast cancer include pain, swelling, warmth and redness throughout the breast, as well as an orange peel texture to the skin referred to as ''peau d'orange''.<ref name="merck"/> Another reported symptom complex of breast cancer is [[Paget's disease of the breast]]. This [[syndrome]] presents as [[eczema]]toid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.<ref name="nci paget">{{cite web |author=[[National Cancer Institute]] |month=June 27, |year=2005 |title=Paget's Disease of the Nipple: Questions and Answers |url=http://www.cancer.gov/cancertopics/factsheet/Sites-Types/pagets-breast |accessdate=2008-02-06}}</ref> Occasionally, breast cancer presents as [[metastatic]] disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. More common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific," meaning they can also be manifestations of many other illnesses.<ref name="nci metastatic">{{cite web |author=[[National Cancer Institute]] |month=September 1, |year=2004 |title=Metastatic Cancer: Questions and Answers |url=http://www.cancer.gov/cancertopics/factsheet/Sites-Types/metastatic |accessdate=2008-02-06}}</ref> Most symptoms of breast disorder do not turn out to represent underlying breast cancer. [[Benign breast diseases]] such as [[mastitis]] and [[fibroadenoma]] of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.<ref name="merck breasts">{{cite web |author=[[Merk Manual of Diagnosis and Therapy]] |month=February |year=2003 |title=Breast Disorders: Introduction |url=http://www.merck.com/mmhe/sec22/ch251/ch251a.html |accessdate=2008-02-05}}</ref> ==Epidemiology and etiology== {{main|Epidemiology and etiology of breast cancer}} [[Epidemiology|Epidemiological]] risk factors for a disease can provide important clues as to the [[etiology]], or cause, of a disease. The first [[case-control]]led study on breast cancer epidemiology was done by [[Janet Lane-Claypon]], who published a comparative study in 1926 of 500 breast cancer cases and 500 control patients of the same background and lifestyle for the British Ministry of Health.<ref name='Lane-Claypon 1926'>{{cite book | last = Lane-Claypon | first = Janet Elizabeth | authorlink = Janet Lane-Claypon | coauthors = | title = A further report on cancer of the breast, with special reference to its associated antecedent conditions | publisher = Her Majesty’s Stationery Office (HMSO) |date=1926 | location = London, Greater London | pages = | url = | oclc = 14713036 | doi = | id = | isbn = }}</ref>{{Verify source|date=January 2008}}<ref name="isbn3-7643-6818-7">{{cite book | author = Alfredo Morabia | title = A History of Epidemiologic Methods and Concepts | publisher = Birkhauser | location = Boston | year = 2004 | pages = 301-302 | isbn = 3-7643-6818-7 | oclc = | doi = | url = http://books.google.com/books?id=E-OZbEmPSTkC&pg=PA301&lpg=PA301&dq=%22lane+claypon%22+%22further+report+*+cancer%22&source=web&ots=jSQWua-Sx0&sig=3arOIXuwGU_w_Omza11lEDj2TEo#PPA301,M1 | accessdate = 2007-12-31}}</ref> Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors. Some of these factors include: # Lesions to [[DNA]] such as [[Mutation|genetic mutations]]. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.<ref name="pmid16675129">{{cite journal |author=Cavalieri E, Chakravarti D, Guttenplan J, ''et al'' |title=Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention |journal=Biochim. Biophys. Acta |volume=1766 |issue=1 |pages=63–78 |year=2006 |pmid=16675129 |doi=10.1016/j.bbcan.2006.03.001}}</ref> Beyond the contribution of estrogen, research has implicated [[viral oncogenesis]] and the contribution of [[ionizing radiation]] in causing genetic mutations.{{Fact|date=February 2008}} # Failure of [[immune surveillance]], a theory in which the immune system removes malignant cells throughout one's life.<ref name="immune">{{cite web |author=Farlex |year=2005 |title=The Free Dictionary: Immunological Surveilliance |url=http://medical-dictionary.thefreedictionary.com/immunological+surveillance">immunological surveillance |accessdate=2008-02-10}}</ref> # Abnormal [[growth factor]] signaling in the interaction between [[stromal cell]]s and [[epithelial cell]]s can facilitate malignant cell growth. For example, tumors can induce blood vessel growth ([[angiogenesis]]) by secreting various growth factors further facilitating cancer growth.{{Fact|date=February 2008}} # Inherited defects in [[DNA repair genes]], such as ''BRCA1'', ''BRCA2''<ref name="acs bc facts 2005-6">{{cite web |author=American Cancer Society |year=2005 |title=Breast Cancer Facts & Figures 2005-2006 |url=http://www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf |accessdate=2007-04-26}}</ref> and ''p53''.{{Fact|date=February 2008}} Although many epidemiological risk factors have been identified, the cause of any individual breast cancer is often unknowable. In other words, epidemiological research informs the patterns of breast cancer incidence across certain populations, but not in a given individual. The primary risk factors that have been identified are sex,<ref name="Giordano">{{cite journal | last = Giordano | first = Sharon H | authorlink = | coauthors = Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN | title = Breast carcinoma in men | journal = Cancer | volume = 101 | issue = 1 | pages = 51–57 | publisher =American Cancer Society |date=May 2004 | url= http://www3.interscience.wiley.com/cgi-bin/fulltext/108565241/HTMLSTART | doi = | id = | accessdate = }}</ref> age,<ref>{{cite web | title = Individual Risk Factors| publisher = BreastCancer.org | url = http://www.breastcancer.org/symptoms/understand_bc/who_gets/ind_risk.jsp | accessdate = 2007-03-11}}</ref> childbearing, hormones,<ref>{{cite journal |author=Yager JD |coauthors=Davidson NE |title=Estrogen carcinogenesis in breast cancer |journal=New Engl J Med |volume=354 |issue=3 |year=2006 |pages=270–82 |pmid=16421368 | doi = 10.1056/NEJMra050776}}</ref> a high-fat diet,<ref>{{cite journal | author = Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK, et al. | title = Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study (WINS) | journal =J Natl Cancer Inst | volume =98 | issue =24 | pages =1767–1776 | pmid = 17179478 | url =}}</ref> alcohol intake,<ref name=Boffetta_2006>{{cite journal | last = Boffetta | first = Paolo | coauthors = Hashibe, Mia; La Vecchia, Carlo; Zatonski, Witold; Rehm, Jürgen | title = The burden of cancer attributable to alcohol drinking | journal = International Journal of Cancer | volume = 119 | issue = 4 | pages = 884–887 | publisher = Wiley-Liss, Inc |date=2006-03-23 | url = http://www3.interscience.wiley.com/cgi-bin/abstract/112550783/ABSTRACT | doi = 10.1002/ijc.21903 | accessdate = 2006-10-09 | pmid=16557583 }}</ref><ref> [http://news.yahoo.com/s/nm/20080413/hl_nm/breastcancer_alcohol_dc;_ylt=AtGS284WPB.IUGjuanLfVhas0NUE]</ref> obesity,<ref>BBC report [http://news.bbc.co.uk/1/hi/health/5171838.stm Weight link to breast cancer risk]</ref> and environmental factors such as tobacco use, radiation<ref name="acs bc facts 2005-6"/> and shiftwork.<ref>WHO international Agency for Research on Cancer [http://www.iarc.fr/ENG/Press_Releases/pr180a.html Press Release No. 180], December 2007.</ref> No etiology is known for 95% of breast cancer cases, while approximately 5% of new breast cancers are attributable to hereditary syndromes.<ref name=Madigan_1995>{{cite journal | author = Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN | title = Proportion of breast cancer cases in the United States explained by well-established risk factors | journal = J. Natl. Cancer Inst. | volume = 87 | issue = 22 | pages = 1681–5 | year = 1995 | pmid = 7473816 | doi = 10.1093/jnci/87.22.1681}}</ref> In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occurs.<ref name=Venkitaraman_2002>{{cite journal |last= Venkitaraman |first= AR |title= cancer susceptibility and the functions of BRCA1 and BRCA2 |year= 2002 |journal= Cell |volume= 108 | issue= 2 | pages= 171–82 |doi= 10.1016/S0092-8674(02)00615-3 }}</ref> == Prevention == Lower age of first childbirth (less than 24 years maternal age), having more children (about 7% lowered risk per child), and breastfeeding (4% per breastfeeding year, with an average [[relative risk]] around 0.7<ref>{{cite journal |author=McTiernan A, Thomas DB |title=Evidence for a protective effect of lactation on risk of breast cancer in young women. Results from a case-control study |journal=Am. J. Epidemiol. |volume=124 |issue=3 |pages=353–8 |year=1986 |month=September |pmid=3740036 |doi= |url=http://aje.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=3740036}}</ref><ref>{{cite journal |author=Byers T, Graham S, Rzepka T, Marshall J |title=Lactation and breast cancer. Evidence for a negative association in premenopausal women |journal=Am. J. Epidemiol. |volume=121 |issue=5 |pages=664–74 |year=1985 |month=May |pmid=4014158 |doi= |url=http://aje.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=4014158}}</ref>) have all been correlated to lowered breast cancer risk in large studies.<ref name="pmid10213546">{{cite journal |coauthors=Collaborative Group on Hormonal Factors in Breast Cancer. |year=1997 |month= |title=Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer |journal=Lancet |volume=350 |issue=9084 |pages=1047–59 |pmid=10213546 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673697082330 |accessdate= 2008-04-08|doi=10.1016/S0140-6736(97)08233-0}}</ref> In addition, exercising three times a week for one hour each has been found to lower breast cancer by up to 40%.{{Fact|date=April 2008}} === Phytoestrogens and soy === [[Phytoestrogens]] such as found in [[soybeans]] have been extensively studied in animal and human ''in-vitro'' and epidemiological studies. The literature support the following conclusions: # Plant estrogen intake, such as from soy products, in early adolescence may protect against breast cancer later in life.<ref name="pmid17158751">{{cite journal |author=Rice S, Whitehead SA |title=Phytoestrogens and breast cancer--promoters or protectors? |journal=Endocr. Relat. Cancer |volume=13 |issue=4 |pages=995–1015 |year=2006 |pmid=17158751 |doi=10.1677/erc.1.01159}}</ref> # Plant estrogen intake later in life is not likely to influence breast cancer incidence either positively or negatively.<ref>{{cite journal |author=Gikas PD, Mokbel K |title=Phytoestrogens and the risk of breast cancer: a review of the literature |journal=Int J Fertil Womens Med |volume=50 |issue=6 |pages=250–8 |year=2005 |pmid=16526415 |doi= |url=}}</ref> === Folic acid (folate) === {{main|Folic acid#Folic acid and cancer}} {{Disputed|date=March 2008}} Studies have found that "folate intake counteracts breast cancer risk associated with alcohol consumption"<ref>Mayo Clinic news release [[June 26]] 2001 [http://www.mayoclinic.org/news2001-rst/857.html "Folate Intake Counteracts Breast Cancer Risk Associated with Alcohol Consumption"]</ref> and "women who drink alcohol and have a high folate intake are not at increased risk of cancer."<ref>Boston University,[http://www.bu.edu/aodhealth/issues/issue_may04/html/04-0506-ellison_baily.html ''Folate, Alcohol, and Cancer Risk'']</ref><ref>{{cite journal |author=Bailey LB |title=Folate, methyl-related nutrients, alcohol, and the MTHFR 677C-->T polymorphism affect cancer risk: intake recommendations |journal=J. Nutr. |volume=133 |issue=11 Suppl 1 |pages=3748S–3753S |year=2003 |month=November |pmid=14608109 |doi= |url=http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=14608109}}</ref><ref name="Zhang_1999">{{cite journal |author=Zhang S, Hunter D, Hankinson S, Giovannucci E, Rosner B, Colditz G, Speizer F, Willett W |title=A prospective study of folate intake and the risk of breast cancer |journal=JAMA |volume=281 |issue=17 |pages=1632–7 |year=1999 |pmid=10235158 | doi = 10.1001/jama.281.17.1632}}</ref> A prospective study of over 17,000 women found that those who consume 40 grams of alcohol (about 3-4 drinks) per day have a higher risk of breast cancer. However, in women who take 200 micrograms of folate (folic acid or Vitamin B9) every day, the risk of breast cancer drops below that of alcohol abstainers.<ref> Baglietto, Laura, et al. Does dietary folate intake modify effect of alcohol consumption on breast cancer risk? Prospective cohort study. British Medical Journal, August 8, 2005 </ref> Folate is involved in the synthesis, repair, and functioning of DNA, the body’s genetic map, and a deficiency of folate may result in damage to DNA that may lead to cancer.<ref name="Oldref_43">{{cite journal | author=Jennings E. | title=Folic acid as a cancer preventing agent | journal=Medical Hypotheses | volume=45 | issue=3 | year=1995 | pages=297–303 | pmid=8569555 | doi = 10.1016/0306-9877(95)90121-3}}</ref> In addition to breast cancer, studies have also associated diets low in folate with increased risk of [[pancreatic cancer|pancreatic]], and colon cancer.<ref name="Oldref_45">{{cite journal | author=Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs C, Rosner BA, Speizer FE, Willett WC. | title=Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study | journal=Annals of Internal Medicine | volume=129 | issue=7 | year=1998 | pages=517–524 | pmid=9758570}}</ref><ref> name="Oldref_42">{{cite journal | author=Freudenheim JL, Grahm S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G | title=Folate intake and carcinogenesis of the colon and rectum | journal=International Journal of Epidemiology | volume=20 | issue=2 | year=1991 | pages=368–374 | pmid=1917236 | doi = 10.1093/ije/20.2.368}}</ref> Foods rich in folate include [[citrus fruit]]s, citrus juices, dark [[green leafy vegetable]]s (such as [[spinach]]), dried [[bean]]s, and [[pea]]s. Vitamin B9 can also be taken in a multivitamin pill. ===Avoiding exposure to secondhand tobacco smoke=== Breathing [[secondhand smoke]] increases breast cancer risk by 70% in younger, primarily pre-menopausal women. The [[California Environmental Protection Agency]] has concluded that [[passive smoking]] causes breast cancer<ref name="calepa2005">[http://repositories.cdlib.org/context/tc/article/1194/type/pdf/viewcontent/ California Environmental Protection Agency: Air Resources Board, "Proposed Identification of Environmental Tobacco Smoke as a Toxic Air Contaminant" (June 24, 2005)]; on January 26, 2006, the Air Resources Board, following a lengthy review and public outreach process, determined ETS to be a Toxic Air Contaminant (TAC).</ref> and the US [[Surgeon General]]<ref>[http://www.surgeongeneral.gov/library/secondhandsmoke/ U.S. Department of Health and Human Services. "The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General", 2006]</ref> has concluded that the evidence is "suggestive," one step below causal. There is some evidence that exposure to tobacco smoke is most problematic between puberty and first childbirth. The reason that breast tissue appears most sensitive to chemical carcinogens in this phase is that breast cells are not fully differentiated until lactation.<ref>J. Russo, I. Russo. "Molecular Basis of Breast Cancer: Prevention and Treatment," Springer, 2003</ref> ===Oophorectomy and mastectomy=== Prophylactic [[oophorectomy]] (removal of ovaries), in high-risk individuals, when child-bearing is complete, reduces the risk of developing breast cancer by 60%, as well as reducing the risk of developing ovarian cancer by 96%.<ref name=Kauff_2002>{{cite journal |author=Kauff N, Satagopan J, Robson M, Scheuer L, Hensley M, Hudis C, Ellis N, Boyd J, Borgen P, Barakat R, Norton L, Castiel M, Nafa K, Offit K |title=Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation |journal=N Engl J Med |volume=346 |issue=21 |pages=1609–15 |year=2002 |url=http://content.nejm.org/cgi/content/abstract/NEJMoa020119v1 |pmid=12023992 | doi = 10.1056/NEJMoa020119}}</ref> ===Medications=== [[Hormonal therapy (oncology)|Hormonal therapy]] has been used for chemoprevention in individuals at high risk for breast cancer. In 2002, a [[clinical practice guideline]] by the [[US Preventive Services Task Force]] (USPSTF) recommended that "clinicians discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse effects of chemoprevention" with a grade B recommendation.<ref name='USPSTF Ratings'> {{cite web|url=http://www.ahrq.gov/clinic/3rduspstf/ratings.htm |title=Guide to Clinical Preventive Services, Third Edition: Periodic Updates, 2000-2003 |accessdate=2007-10-07 |work=Agency for Healthcare Research and Quality |publisher=US Preventive Services Task Force }}</ref>{{Verify source|date=October 2007}}<ref name="pmid12093249">{{cite journal |author= |title=Chemoprevention of breast cancer: recommendations and rationale |journal=Ann. Intern. Med. |volume=137 |issue=1 |pages=56–8 |year=2002 |pmid=12093249 |doi=|url=http://www.annals.org/cgi/content/full/137/1/56}}</ref><ref name="pmid12093250">{{cite journal |author=Kinsinger LS, Harris R, Woolf SH, Sox HC, Lohr KN |title=Chemoprevention of breast cancer: a summary of the evidence for the U.S. Preventive Services Task Force |journal=Ann. Intern. Med. |volume=137 |issue=1 |pages=59–69 |year=2002 |url=http://www.annals.org/cgi/content/full/137/1/59|pmid=12093250 |doi=}}</ref> ====Selective estrogen receptor modulators (SERMs)==== The guidelines{{Clarifyme|date=March 2008}} were based on studies of [[Selective estrogen receptor modulator|SERM]]s from the MORE, BCPT P-1, and Italian trials. In the MORE trial, the [[relative risk reduction]] for raloxifene was 76%.<ref name="pmid10376571">{{cite journal |author=Cummings SR, Eckert S, Krueger KA, ''et al'' |title=The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation |journal=JAMA |volume=281 |issue=23 |pages=2189–97 |year=1999 |pmid=10376571| doi = 10.1001/jama.281.23.2189}}</ref> The P-1 preventative study demonstrated that tamoxifen can prevent breast cancer in high-risk individuals. The relative risk reduction was up to 50% of new breast cancers, though the cancers prevented were more likely estrogen-receptor positive (this is analogous to the effect of [[finasteride]] on the prevention of [[prostate cancer]], in which only low-grade prostate cancers were prevented).<ref name="pmid16288118">{{cite journal |author=Fisher B, Costantino JP, Wickerham DL, ''et al'' |title=Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study |journal=J. Natl. Cancer Inst. |volume=97 |issue=22 |pages=1652–62 |year=2005 |pmid=16288118 |doi=10.1093/jnci/dji372}}</ref><ref name="pmid9747868">{{cite journal |author=Fisher B, Costantino JP, Wickerham DL, ''et al'' |title=Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study |journal=J. Natl. Cancer Inst. |volume=90 |issue=18 |pages=1371–88 |year=1998 |pmid=9747868| doi = 10.1093/jnci/90.18.1371}}</ref> The Italian trial showed benefit from tamoxifen.<ref name="pmid17470740">{{cite journal |author=Veronesi U, Maisonneuve P, Rotmensz N, ''et al'' |title=Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy |journal=J. Natl. Cancer Inst. |volume=99 |issue=9 |pages=727–37 |year=2007 |pmid=17470740 |doi=10.1093/jnci/djk154}}</ref> Additional [[randomized controlled trials]] have been published since the guidelines. The IBIS trial found benefit from tamoxifen.<ref name="pmid17312304">{{cite journal |author=Cuzick J, Forbes JF, Sestak I, ''et al'' |title=Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial |journal=J. Natl. Cancer Inst. |volume=99 |issue=4 |pages=272–82 |year=2007 |pmid=17312304 |doi=10.1093/jnci/djk049}}</ref> In 2006, the [[NSABP]] STAR trial demonstrated that raloxifene had equal efficacy in preventing breast cancer compared with tamoxifen, but that there were fewer side effects with raloxifene.<ref name="pmid16754727">{{cite journal |author=Vogel VG, Costantino JP, Wickerham DL, ''et al'' |title=Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial |journal=JAMA |volume=295 |issue=23 |pages=2727–41 |year=2006 |pmid=16754727 |doi=10.1001/jama.295.23.joc60074}}</ref> The RUTH Trial concluded that "benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke".<ref name="pmid16837676">{{cite journal |author=Barrett-Connor E, Mosca L, Collins P, ''et al'' Raloxifene Use for The Heart (RUTH) Trial Investigators. |title=Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women |journal=N. Engl. J. Med. |volume=355 |issue=2 |pages=125–37 |year=2006 |pmid=16837676 |doi=10.1056/NEJMoa062462}}</ref> On [[September 14]], 2007, the [[US Food and Drug Administration]] approved [[raloxifene]] (Evista) to prevent invasive breast cancer in postmenopausal women.<ref>[http://afp.google.com/article/ALeqM5iN5TpHWbHfPZMBgXvaIyVlgc-XZQ AFP.google.com, US approves Lilly's Evista for breast cancer prevention]</ref> ==Screening== {{main|Breast cancer screening}} Breast cancer screening is an attempt to find unsuspected cancers. The most common screening methods are self and clinical breast exams, x-ray mammography, and breast Magnetic resonance imaging (MRI) ===X-ray mammography=== Mammography is still the modality of choice for screening of early breast cancer, since it is relatively fast, reasonably accurate, and widely available in developed countries. Due to the high incidence of breast cancer among older women, screening is now recommended in many countries. Recommended screening methods include [[breast self-examination]] and [[mammography]]. Mammography has been estimated to reduce breast cancer-related mortality by 20-30%.<ref>{{cite journal | author = Elwood J, Cox B, Richardson A | title = The effectiveness of breast cancer screening by mammography in younger women | journal = Online J Curr Clin Trials | volume = Doc No 32 | issue = | pages = [23,227 words; 195 paragraphs] | year = | pmid = 8305999}}</ref> Routine (annual) mammography of women older than age 40 or 50 is recommended by numerous organizations as a screening method to diagnose early breast cancer and has demonstrated a protective effect in multiple clinical trials.<ref>{{cite journal | author = Fletcher S, Black W, Harris R, Rimer B, Shapiro S | title = Report of the International Workshop on Screening for Breast Cancer | journal = J Natl Cancer Inst | volume = 85 | issue = 20 | pages = 1644–56 | year = 1993 | pmid = 8105098 | doi = 10.1093/jnci/85.20.1644}}</ref> The evidence in favor of mammographic screening comes from eight randomized clinical trials from the 1960s through 1980s. Many of these trials have been criticised for methodological errors, and the results were summarized in a review article published in 1993.<ref name=Fletcher_1993>{{cite journal | author = Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S | title = Report of the International Workshop on Screening for Breast Cancer | journal = J. Natl. Cancer Inst. | volume = 85 | issue = 20 | pages = 1644–56 | year = 1993 | pmid = 8105098 | doi = 10.1093/jnci/85.20.1644}}</ref> Improvements in mortality due to screening are hard to measure; similar difficulty exists in measuring the impact of [[Pap smear]] testing on [[cervical cancer]], though worldwide, the impact of that test is likely enormous. Nationwide mortality due to cancer before and after the institution of a screening test is a surrogate indicator about the effectiveness of screening, and results of mammography are favorable. [[Image:Mammo breast cancer.jpg|thumb|right|Normal (left) versus cancerous (right) mammography image.]] The U.S. [[National Cancer Institute]] recommends screening mammography every one to two years beginning at age 40.<ref name="NCI_MMG_Screening">{{cite web |url=http://www.cancer.gov/newscenter/mammstatement31jan02 |title=NCI Statement on Mammography Screening - National Cancer Institute |accessdate=2007-09-11 |format= |work=}}</ref> In the UK, women are invited for screening once every three years beginning at age 50. Women with one or more first-degree relatives (mother, sister, daughter) with premenopausal breast cancer should begin screening at an earlier age. It is usually suggested to start screening at an age that is 10 years less than the age at which the relative was diagnosed with breast cancer. A clinical practice guideline by the US Preventive Services Task Force recommended "screening mammography, with or without clinical breast examination (CBE), every 1 to 2 years for women aged 40 and older."<ref name="pmid12204019">{{cite journal |author= |title=Screening for breast cancer: recommendations and rationale |journal=Ann. Intern. Med. |volume=137 |issue=5 Part 1 |pages=344–6 |year=2002 |pmid=12204019 |doi=|url=http://www.annals.org/cgi/content/full/137/5_Part_1/344}}</ref> The Task Force gave a grade B recommendation.<ref name='USPSTF Ratings'/>{{Verify source|date=October 2007}} In 2005, 67.9% of all U.S. women age 40–64 had a mammogram in the past two years (74.5% of women with private [[health insurance#Health insurance in the United States|health insurance]], 56.1% of women with [[Medicaid]] insurance, 38.1% of currently [[Health care in the United States#Inequities|uninsured]] women, and 32.9% of women uninsured for > 12 months).<!-- --><ref name="Ward 2008">{{cite journal |author=Ward E, Halpern M, Schrag N, Cokkinides V, DeSantis C, Bandi P, Siegel R, Stewart A, Jemal A |month=Jan-Feb |year=2008 |title=Association of insurance with cancer care utilization and outcomes |journal=CA Cancer J Clin |volume=58 |issue=1 |url=http://caonline.amcancersoc.org/cgi/content/full/CA.2007.0011v1 |pmid=18096863 |doi=10.3322/CA.2007.0011 |doi_brokendate=2008-06-26}}</ref> ===Criticisms of screening mammography=== Several scientific groups however have expressed concern about the public's perceptions of the benefits of breast screening.<ref>{{cite news | first= | last= | coauthors= | title=Women 'misjudge screening benefits' | date= Monday, 15 October, 2001 | publisher= | url =http://news.bbc.co.uk/1/hi/health/1601267.stm | work =BBC | pages = | accessdate = 2007-04-04 | language = }}</ref> In 2001, a controversial review published in [[The Lancet]] claimed that "there is no reliable evidence that screening for breast cancer reduces mortality".<ref>{{cite journal |author=Olsen O, Gøtzsche P |title=Cochrane review on screening for breast cancer with mammography |journal=Lancet |volume=358 |issue=9290 |pages=1340–2 |year=2001 |pmid=11684218 | doi = 10.1016/S0140-6736(01)06449-2}}</ref><ref>{{cite news | first= | last= | coauthors= | title=New concerns over breast screening | date= Thursday, 18 October, 2001 | publisher= | url =http://news.bbc.co.uk/1/hi/health/1607113.stm | work =BBC | pages = | accessdate = 2007-04-04 | language = }}</ref>The Cochrane Collaboration concluded, "for every 2000 women invited for screening throughout 10 years, one will have her life prolonged. In addition, 10 healthy women, who would not have been diagnosed if there had not been screening, will be diagnosed as breast cancer patients and will be treated unnecessarily. It is thus not clear whether screening does more good than harm."<ref>[http://www.cochrane.org/reviews/en/ab001877.html Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD001877. DOI: 10.1002/14651858.CD001877.pub2]</ref> False positives are a major problem of mammographic breast cancer screening. Data reported in the UK Million Woman Study indicates that if 134 mammograms are performed, 20 women will be called back for suspicious findings, and four biopsies will be necessary, to diagnose one cancer. Recall rates are higher in the U.S. than in the UK.<ref name="pmid15814020">{{cite journal |author=Smith-Bindman R, Ballard-Barbash R, Miglioretti DL, Patnick J, Kerlikowske K |title=Comparing the performance of mammography screening in the USA and the UK |journal=Journal of medical screening |volume=12 |issue=1 |pages=50–4 |year=2005 |pmid=15814020 |doi=10.1258/0969141053279130}}</ref> The contribution of mammography to the early diagnosis of cancer is controversial, and for those found with benign lesions, mammography can create a high psychological and financial cost. ====Mammography in women less than 50 years old==== Part of the difficulty in interpreting mammograms in younger women stems from the problem of breast density. Radiographically, a dense breast has a preponderance of glandular tissue, and younger age or [[estrogen]] [[hormone replacement therapy]] contribute to mammographic breast density. After menopause, the breast glandular tissue gradually is replaced by fatty tissue, making mammographic interpretation much more accurate. Some authors speculate that part of the contribution of estrogen hormone replacement therapy to breast cancer mortality arises from the issue of increased mammographic breast density. Breast density is an independent adverse prognostic factor on breast cancer prognosis. A [[systematic review]] by the [[American College of Physicians]] concluded "Although few women 50 years of age or older have risks from mammography that outweigh the benefits, the evidence suggests that more women 40 to 49 years of age have such risks".<ref name="pmid17404354">{{cite journal |author=Armstrong K, Moye E, Williams S, Berlin JA, Reynolds EE |title=Screening mammography in women 40 to 49 years of age: a systematic review for the American College of Physicians |journal=Ann. Intern. Med. |volume=146 |issue=7 |pages=516–26 |year=2007 |pmid=17404354 |doi=}}</ref>. A report released November 27, 2007 by the Journal of the National Cancer Institute showed that the formula doctors use to calculate a woman's risk of breast cancer underestimates the danger for black women most of the time and especially for those age 50 and older — the age when they are most likely to benefit from screening tests and protective drugs, according to the first major reassessment of the widely used tool.<ref name="pmid18000216">{{cite journal | author = Chlebowski RT, Anderson GL, Lane DS, Aragaki AK, Rohan T, Yasmeen S, Sarto G, Rosenberg CA, Hubbell FA | title = Predicting risk of breast cancer in postmenopausal women by hormone receptor status | journal = J. Natl. Cancer Inst. | volume = 99 | issue = 22 | pages = 1695–705 | year = 2007 | pmid = 18000216 | doi = 10.1093/jnci/djm224| url = http://jnci.oxfordjournals.org/cgi/content/abstract/99/22/1695 | accessdate = 2007-12-02}}</ref> ===Enhancements to mammography=== CAD is especially established in US and the Netherlands. It is used in addition to the human evaluation of the diagnostician. ===Breast MRI=== [[Magnetic resonance imaging]] (MRI) has been shown to detect cancers not visible on mammograms, but has long been regarded to have disadvantages. For example, although it is 27-36% more sensitive, it is less specific than mammography.<ref>{{cite journal | author = Hrung J, Sonnad S, Schwartz J, Langlotz C | title = Accuracy of MR imaging in the work-up of suspicious breast lesions: a diagnostic meta-analysis | journal = Acad Radiol | volume = 6 | issue = 7 | pages = 387–97 | year = 1999 | pmid = 10410164 | doi = 10.1016/S1076-6332(99)80189-5}}</ref> As a result, MRI studies will have more [[Type I and type II errors|false positives]] (up to 5%), which may have undesirable financial and psychological costs. It is also a relatively expensive procedure, and one which requires the intravenous injection of a chemical agent (from which there are side effects, potentially serious in a small number of people) to be effective. Proposed indications for using MRI for screening include:<ref>{{cite journal | author = Morrow M | title = Magnetic resonance imaging in breast cancer: one step forward, two steps back? | journal = JAMA | volume = 292 | issue = 22 | pages = 2779–80 | year = 2004 | pmid = 15585740 | doi = 10.1001/jama.292.22.2779}}</ref> *Strong family history of breast cancer *Patients with BRCA-1 or BRCA-2 tumour suppressor gene mutations *Evaluation of women with breast implants *History of previous lumpectomy or breast biopsy surgeries *Axillary metastasis with an unknown primary tumor *Very dense or scarred breast tissue However, two studies published in 2007 demonstrated the strengths of MRI-based screening: *In March 2007, an article published in the ''[[New England Journal of Medicine]]'' demonstrated that in 3.1% of patients with breast cancer, whose [[contralateral]] breast was clinically and mammographically tumor-free, MRI could detect breast cancer. [[Sensitivity (tests)|Sensitivity]] for detection of breast cancer in this study was 91%, [[Specificity (tests)|specificity]] 88%.<ref>{{cite journal | author = Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, Peacock S, Smazal SF, Maki DD, Julian TB, DePeri ER, Bluemke DA, Schnall MD | title = MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer| journal = N Engl J Med.| volume = 356 | issue = 13| pages = 1295–1303| year = 2007 | pmid = 17392300 | doi = 10.1056/NEJMoa065447}}</ref> *In August 2007, an article published in ''The Lancet'' compared MRI breast cancer screening to conventional mammographic screening in 7,319 women. MRI screening was highly more sensitive (97% in the MRI group vs. 56% in the mammography group) in recognizing early high-grade Ductal Carcinoma in situ (DCIS), the most important precursor of invasive carcinoma. Despite the high sensitivity, MRI screening had a [[positive predictive value]] of 52%, which is totally accepted for cancer screening tests.<ref>{{cite journal | author = Kuhl CK, Schrading S, Bieling HB, Wardelmann E, Leutner CC, Koenig R, Kuhn W, Schild HH| title = MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study| journal = The Lancet | volume = 370 | issue = 9586 | pages = 485–492 | year = 2007| doi = 10.1016/S0140-6736(07)61232-X}}</ref> The author of a comment published in the same issue of ''The Lancet'' concludes that "MRI outperforms mammography in tumour detection and diagnosis."<ref>{{cite journal | author = Boetes C, Mann RM| title = Ductal carcinoma in situ and breast MRI| journal = The Lancet | volume = 370 | issue = 9586 | pages = 459–460 | year = 2007| doi = 10.1016/S0140-6736(07)61207-0}}</ref> ===Breast self-exam=== [[Breast self-examination]] (BSE) was widely discussed in the 1990s as a useful modality for detecting breast cancer at an earlier stage of presentation. A large clinical trial in China reduced enthusiasm for breast self-exam. In the trial, reported in the ''Journal of the National Cancer Institute'' first in 1997 and updated in 2002, 132,979 female Chinese factory workers were taught by nurses at their factories to perform monthly breast self-exam, while 133,085 other workers were not taught self-exam. The women taught self-exam tended to detect more breast nodules, but their breast cancer mortality rate was no different from that of women in the control group. In other words, women taught breast self-exam were mostly likely to detect benign breast disease, but were just as likely to die of breast cancer.<ref name="pmid12359854">{{cite journal |author=Thomas DB, Gao DL, Ray RM, ''et al'' |title=Randomized trial of breast self-examination in Shanghai: final results |journal=J. Natl. Cancer Inst. |volume=94 |issue=19 |pages=1445–57 |year=2002 |pmid=12359854 |doi=}}</ref> In 2003, the [[American Cancer Society]] relegated structured BSE to an 'optional' method of detecting breast cancer, citing self awareness as more important than structured self exams based on recent research.<ref name="acs bc facts 2005-6"/> ===Genetic testing=== A clinical practice guideline by the US Preventive Services Task Force :<ref name="pmid12204019">{{cite journal |author= |title=Screening for breast cancer: recommendations and rationale |journal=Ann. Intern. Med. |volume=137 |issue=5 Part 1 |pages=344–6 |year=2002 |pmid=12204019 |doi=|url=http://www.annals.org/cgi/content/full/137/5_Part_1/344}}</ref> * "recommends against routine referral for [[genetic counseling]] or routine breast cancer susceptibility gene (BRCA) testing for women whose family history is not associated with an increased risk for deleterious mutations in breast cancer susceptibility gene 1 ([[BRCA1]]) or breast cancer susceptibility gene 2 ([[BRCA2]])" The Task Force gave a grade D recommendation.<ref name='USPSTF Ratings'/>{{Verify source|date=October 2007}} *"recommends that women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing." The Task Force gave a grade B recommendation.<ref name='USPSTF Ratings'/>{{Verify source|date=October 2007}} The Task Force noted that about 2% of women have family histories that indicate increased risk as defined by: * For non–Ashkenazi Jewish women, any of the following: ** "2 first-degree relatives with breast cancer, 1 of whom received the diagnosis at age 50 years or younger" ** "3 or more first- or second-degree relatives with breast cancer regardless of age at diagnosis" ** "both breast and ovarian cancer among first- and second- degree relatives" ** "a first-degree relative with bilateral breast cancer" ** "a combination of 2 or more first- or second-degree relatives with ovarian cancer regardless of age at diagnosis" ** "a first- or second-degree relative with both breast and ovarian cancer at any age" ** "a history of breast cancer in a male relative." *"For women of Ashkenazi Jewish heritage, an increased-risk family history includes any first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer." ==Diagnosis== {{Unreferencedsection|date=October 2007}} Breast cancer is diagnosed by the examination of surgically removed breast tissue. A number of procedures can obtain tissue or cells prior to definitive treatment for histological or cytological examination. Such procedures include fine-needle aspiration, nipple aspirates, ductal lavage, core needle biopsy, and local surgical excision. These diagnostic steps, when coupled with radiographic imaging, are usually accurate in diagnosing a breast lesion as cancer. Occasionally, pre-surgical procedures such as fine needle aspirate may not yield enough tissue to make a diagnosis, or may miss the cancer entirely. Imaging tests are sometimes used to detect metastasis and include [[chest X-ray]], [[bone scan]], [[Cat scan]], [[MRI]], and [[Positron emission tomography|PET]] scanning. While imaging studies are useful in determining the presence of metastatic disease, they are not in and of themselves diagnostic of cancer. Only microscopic evaluation of a biopsy specimen can yield a cancer diagnosis. Ca 15.3 (carbohydrate antigen 15.3, epithelial mucin) is a [[tumor marker]] determined in blood which can be used to follow disease activity over time after definitive treatment. Blood tumor marker testing is not routinely performed for the screening of breast cancer, and has poor performance characteristics for this purpose. ==Staging== {{splitsection|Breast cancer staging}} Breast cancer is [[Cancer staging|staged]] according to the TNM system, updated in the [[AJCC]] Staging Manual, now on its sixth edition. Prognosis is closely linked to results of staging, and staging is also used to allocate patients to treatments both in clinical trials and clinical practice. The information for staging is as follows: TX: Primary tumor cannot be assessed. T0: No evidence of tumor. Tis: Carcinoma in situ, no invasion T1: Tumor is 2 cm or less T2: Tumor is more than 2 cm but not more than 5 cm T3: Tumor is more than 5 cm T4: Tumor of any size growing into the chest wall or skin, or inflammatory breast cancer NX: Nearby lymph nodes cannot be assessed N0: Cancer has not spread to regional lymph nodes. N1: Cancer has spread to 1 to 3 axillary or one internal mammary lymph node N2: Cancer has spread to 4 to 9 axillary lymph nodes or multiple internal mammary lymph nodes N3: One of the following applies: Cancer has spread to 10 or more axillary lymph nodes, or Cancer has spread to the lymph nodes under the clavicle (collar bone), or Cancer has spread to the lymph nodes above the clavicle, or Cancer involves axillary lymph nodes and has enlarged the internal mammary lymph nodes, or Cancer involves 4 or more axillary lymph nodes, and tiny amounts of cancer are found in internal mammary lymph nodes on [[sentinel lymph node]] biopsy. MX: Presence of distant spread (metastasis) cannot be assessed. M0: No distant spread. M1: Spread to distant organs, not including the supraclavicular lymph node, has occurred '''Summary of stages:''' * ''Stage 0'' - [[Carcinoma in situ]] * ''Stage I'' - Tumor (T) does not involve axillary lymph nodes (N). * ''Stage IIA'' – T 2-5 cm, N negative, or T <2 cm and N positive. * ''Stage IIB'' – T > 5 cm, N negative, or T 2-5 cm and N positive (< 4 axillary nodes). * ''Stage IIIA'' – T > 5 cm, N positive, or T 2-5 cm with 4 or more axillary nodes * ''Stage IIIB'' – T has penetrated chest wall or skin, and may have spread to < 10 axillary N * ''Stage IIIC'' – T has > 10 axillary N, 1 or more supraclavicular or infraclavicular N, or internal mammary N. * ''Stage IV'' – Distant metastasis (M) Approximately 90% of new breast cancer cases in the US will be classified as a "Stage I" cases, due to early detection and prevention techniques. Early-stage treatment options are different from late-stage options.<ref>Zuckerman, Diana, [http://www.medscape.com/viewarticle/567114 "Treatment Options for Early-Stage Breast Cancer: Information for Primary Care Providers"], Medscape Continuing Medical Education. National Research Center for Women and Families.</ref> Breast lesions are examined for certain markers, notably sex steroid hormone receptors. About two thirds of postmenopausal breast cancers are estrogen receptor positive (ER+) and progesterone receptor positive (PR+).<ref>{{cite journal |author=Rusiecki JA, Holford TR, Zahm SH, Zheng T |title=Breast cancer risk factors according to joint estrogen receptor and progesterone receptor status |journal=Cancer Detect. Prev. |volume=29 |issue=5 |pages=419–26 |year=2005 |pmid=16185815 |doi=10.1016/j.cdp.2005.07.004 |url=}}</ref> Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal therapy. ==Human epidermal growth factor two ([[HER2]])== The breast cancer is also usually tested for the presence of human epidermal growth factor receptor 2, a protein also known as [[HER2]], neu or erbB2. HER2 is a cell-surface protein involved in cell development. In normal cells, HER2 controls aspects of cell growth and division. When activated in cancer cells, HER2 accelerates tumor formation. About 20-30% of breast cancers overexpress HER2. Those patients may be candidates for the drug [[trastuzumab]], both in the postsurgical setting (so-called "[[adjuvant]]" therapy), and in the metastatic setting.<ref>[http://www.cancer.gov/cancertopics/factsheet/therapy/herceptin, accessed 1/30/07 cancer.gov]</ref> ==Treatment== {{main|Breast cancer treatment}} The mainstay of breast cancer treatment is [[surgery]] when the tumor is localized, with possible adjuvant hormonal therapy (with [[tamoxifen]] or an [[aromatase inhibitor]]), [[chemotherapy]], and/or [[radiotherapy]]. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern. This pattern is subject to change, as every two years, a worldwide conference takes place in St. Gallen, Switzerland, to discuss the actual results of worldwide multi-center studies. Depending on clinical criteria (age, type of cancer, size, metastasis) patients are roughly divided to high risk and low risk cases, with each risk category following different rules for therapy. Treatment possibilities include radiation therapy, chemotherapy, hormone therapy, and immune therapy. In planning treatment, doctors can also use PCR tests like [[Oncotype DX]] or [[microarray]] tests like [[MammaPrint]] that predict breast cancer recurrence risk based on gene expression. In February 2007, the MammaPrint test became the first breast cancer predictor to win formal approval from the [[Food and Drug Administration]]. This is a new gene test to help predict whether women with early-stage breast cancer will relapse in 5 or 10 years, this could help influence how aggressively the initial tumor is treated.<ref name="NewsMax">"[http://archive.newsmax.com/archives/articles/2007/2/6/130740.shtml FDA Approves New Breast Cancer Test]". [[Associated Press]], [[February 6]], [[2007]].</ref> [[Interstitial laser thermotherapy]] (ILT) is an innovative method of treating breast cancer in a [[Minimally invasive surgery| minimally invasive]] manner and without the need for surgical removal, and with the absence of any adverse effect on the health and survival of the patient during intermediate followup <ref>{{cite journal | authorlink = Kenneth J. Bloom | title = Laser Therapy of Breast Cancer with 3-Year follow up | journal = The Breast Journal | volume = 10 | number = 3 | pages = 240–243 | date = May 2004 | publisher = Blackwell Publishing | doi = 10.1111/j.1075-122X.2004.21436.x | author = Dowlatshahi, Kambiz; Dieschbourg, Janice J.; Bloom, Kenneth J.}}</ref>. Radiation treatment is also used to help destroy cancer cells that may linger after surgery. Radiation can reduce the risk of recurrence by 50-66% (1/2 - 2/3rds reduction of risk) when delivered in the correct dose. <ref>[http://www.breastcancer.org/treatment/radiation Breastcancer.org Treatment Options]</ref> == Early-stage research == In mice, flaxseed oil reduced the growth and metastasis of breast cancer tumors that were cultured in the laboratory and implanted in mice. In humans, flaxseed oil reduced markers that are associated with cancer growth.<ref>{{cite journal|author=Wang, L et al|title=The inhibitory effect of flaxseed oil on the growth and metastasis of estrogen receptor negative human breast cancer xenografts is attributed to both its lignan and oil components|journal=International Journal of Cancer|volume=116|issue=5|pages=793–8|year=2005|pmid=15849746 | doi = 10.1002/ijc.21067}}</ref><ref>{{cite journal|author=Thompson, LU et al|title=Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer|journal=Clinical Cancer Research|volume=11|issue=10|pages=3828–35|year=2005|pmid=15897583 | doi = 10.1158/1078-0432.CCR-04-2326}}</ref><ref>{{cite journal|author=Chen, J et al|title=Dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen-dependent human breast cancer (mcf-7) in nude mice|journal=Clinical Cancer Research|year=2004|volume=10|issue=22|pages=7703–11|pmid=15570004 | doi = 10.1158/1078-0432.CCR-04-1130}}</ref><ref>{{cite journal|author=Chen, J et al|title=Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor|journal=Nutrition and Cancer|volume=43|issue=2|pages=187–92|year=2002|pmid=12588699 | doi = 10.1207/S15327914NC432_9}}</ref> ==Prognosis== {{Unreferencedsection|date=October 2007}} A prognosis is the medical team's "best guess" in how cancer will affect a patient. There are many prognostic factors associated with breast cancer: staging, tumour size and location, grade, whether disease is systemic (has metastasized, or traveled to other parts of the body), recurrence of the disease, and age of patient. Stage is the most important, as it takes into consideration size, local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. Larger tumours, invasiveness of disease to lymph nodes, chest wall, skin or beyond, and aggressiveness of the cancer cells raise the stage, while smaller tumours, cancer-free zones, and close to normal cell behaviour (grading) lower it. Grading is based on how cultured biopsied cells behave. The closer to normal cancer cells are, the slower their growth and a better prognosis. If cells are not well differentiated, they appear immature, divide more rapidly, and tend to spread. Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 (depending upon the scale used). Younger women tend to have a poorer prognosis than post-menopausal women due to several factors. Their breasts are active with their cycles, they may be nursing infants, and may be unaware of changes in their breasts. Therefore, younger women are usually at a more advanced stage when diagnosed. The presence of estrogen and progesterone receptors in the cancer cell, while not prognostic, is important in guiding treatment. Those who do not test positive for these specific receptors will not respond to [[hormone therapy]]. Likewise, HER2/neu status directs the course of treatment. Patients whose cancer cells are positive for HER2/neu have more aggressive disease and may be treated with trastuzumab, a [[monoclonal antibody]] that targets this protein. ===Psychological aspects of diagnosis and treatment=== The emotional impact of cancer diagnosis, symptoms, treatment, and related issues can be severe. Most larger hospitals are associated with [[cancer support group]]s which can help patients cope with the many issues that come up in a supportive environment with other people with experience with similar issues. Online cancer support groups are also very beneficial to cancer patients, especially in dealing with uncertainty and body-image problems inherent in cancer treatment. Not all breast cancer patients experience their illness in the same manner. Factors such as age can have a significant impact on the way a patient copes with a breast cancer diagnosis. For example, a recent study conducted by researchers at the College of Public Health of the University of Georgia showed that older women may face a more difficult recovery from breast cancer than their younger counterparts.<ref name="pmid17188505"/> As the incidence of breast cancer in women over 50 rises and survival rates increase, breast cancer is increasingly becoming a geriatric issue that warrants both further research and the expansion of specialized cancer support services tailored for specific age groups.<ref name="pmid17188505">{{cite journal |author=Robb C, Haley WE, Balducci L, ''et al'' |title=Impact of breast cancer survivorship on quality of life in older women |journal=Crit. Rev. Oncol. Hematol. |volume=62 |issue=1 |pages=84–91 |year=2007 |month=April |pmid=17188505 |doi=10.1016/j.critrevonc.2006.11.003 |url=}}</ref> ===Racial disparities in diagnosis and treatment=== {{Merge-multiple|Epidemiology and etiology of Breast cancer|Breast cancer treatment|date=October 2007}} Several studies have found that black women in the U.S. are more likely to die from breast cancer even though white women are more likely to be diagnosed with the disease. Even after diagnosis, black women are less likely to get treatment compared to white women.<ref>''[http://dhfs.wisconsin.gov/wcrs/pdf/cancerwi0004.pdf Wisconsin Cancer Incidence and Mortality, 2000-2004]'' Wisconsin Department of Health and Family Services</ref><ref name="pmid17218849">{{cite journal |author=Tammemagi CM |title=Racial/ethnic disparities in breast and gynecologic cancer treatment and outcomes |journal=Curr. Opin. Obstet. Gynecol. |volume=19 |issue=1 |pages=31–6 |year=2007 |pmid=17218849 |doi=10.1097/GCO.0b013e3280117cf8}}</ref><ref name="pmid17285262">{{cite journal |author=Hirschman J, Whitman S, Ansell D |title=The black:white disparity in breast cancer mortality: the example of Chicago |journal=Cancer Causes Control |volume=18 |issue=3 |pages=323–33 |year=2007 |pmid=17285262 |doi=10.1007/s10552-006-0102-y}}</ref> Scholars have advanced several theories for the disparities, including inadequate access to screening, reduced availability of the most advanced surgical and medical techniques, or some biological characteristic of the disease in the African American population.<ref>''[http://badgerherald.com/news/2007/10/24/breast_cancer_rates_.php Breast cancer rates differ in races]'' by Amanda Villa Wednesday, October 24, 2007. Badger Herald</ref> Some studies suggest that the racial disparity in breast cancer outcomes may reflect cultural biases more than biological disease differences.<ref name="pmid12716040">{{cite journal |author=Benjamin M, Reddy S, Brawley OW |title=Myeloma and race: a review of the literature |journal=Cancer Metastasis Rev. |volume=22 |issue=1 |pages=87–93 |year=2003 |pmid=12716040| doi = 10.1023/A:1022268103136}}</ref> Research is currently ongoing to define the contribution of both biological and cultural factors.<ref name="pmid17876835">{{cite journal |author=Demicheli R, Retsky MW, Hrushesky WJ, Baum M, Gukas ID, Jatoi I |title=Racial disparities in breast cancer outcome: insights into host-tumor interactions |journal=Cancer |volume=110 |issue=9 |pages=1880–8 |year=2007 |pmid=17876835 |doi=10.1002/cncr.22998}}</ref><ref name="pmid17218849">{{cite journal |author=Tammemagi CM |title=Racial/ethnic disparities in breast and gynecologic cancer treatment and outcomes |journal=Curr. Opin. Obstet. Gynecol. |volume=19 |issue=1 |pages=31–6 |year=2007 |pmid=17218849 |doi=10.1097/GCO.0b013e3280117cf8}}</ref> ==Metastasis== Most people understand breast cancer as something that happens in the breast. However it can metastasize (spread) via lymphatics to nearby lymph nodes, usually those under the arm. That is why surgery for breast cancer always involves some type of surgery for the glands under the arm &mdash; either axillary clearance, sampling, or sentinel node biopsy. Breast cancer can also spread to other parts of the body via blood vessels or the lymphatic system. So it can spread to the lungs, pleura (the lining of the lungs), liver, brain, and most commonly to the bones.<ref name="pmid17158753">{{cite journal |author=Lacroix M |title=Significance, detection and markers of disseminated breast cancer cells |journal=Endocr Relat Cancer |volume=13 |issue=4 |pages=1033–67 |year=2006 |pmid=17158753| doi = 10.1677/ERC-06-0001}}</ref> Seventy percent of the time that breast cancer spreads to other locations, it spreads to bone, especially the vertebrae and the long bones of the arms, legs, and ribs. Breast cancer cells "set up house" in the bones and form tumors. Usually when breast cancer spreads to bone, it eats away healthy bone, causing weak spots, where the bones can break easily. That is why breast cancer patients are often seen wearing braces or using a wheelchair, and have aching bones. When breast cancer is found in bones, it has usually spread to more than one site. At this stage, it is treatable, often for many years, but it is not curable. Like normal breast cells, these tumors in the bone often thrive on female hormones, especially estrogen. Therefore treatment with medicines that lower estrogen levels may be prescribed. ==History== {{Unreferencedsection|date=October 2007}} Breast cancer may be one of the oldest known forms of cancer tumors in humans. The oldest description of cancer was discovered in Egypt and dates back to approximately 1600 BC. The [[Edwin Smith Papyrus]] describes 8 cases of tumors or ulcers of the breast that were treated by [[cauterization]].The writing says about the disease, "There is no treatment."<ref>{{cite web | title = The History of Cancer | work = American Cancer Society |date=2002-03-25 | url = http://www.cancer.org/docroot/CRI/content/CRI_2_6x_the_history_of_cancer_72.asp?sitearea=CRI | accessdate = 2006-10-09 }}</ref> For centuries, physicians described similar cases in their practises, with the same sad conclusion. It wasn't until doctors achieved greater understanding of the circulatory system in the 17th century that they could establish a link between breast cancer and the [[lymph nodes]] in the armpit. The French surgeon [[Jean Louis Petit]] (1674-1750) and later the Scottish surgeon [[Benjamin Bell]] (1749-1806) were the first to remove the lymph nodes, breast tissue, and underlying chest muscle. Their successful work was carried on by [[William Stewart Halsted]] who started performing [[radical mastectomy|mastectomies]] in 1882. He became known for his Halsted radical mastectomy, a surgical procedure that remained popular up to the 1970s. ==Cultural references== [[Image:Pink ribbon.svg| 80px | right]] In the month of [[Breast Cancer Awareness Month|October]], breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease.<ref>{{cite web | title = Breast Cancer Awareness Month | url = http://www.nbcam.com/ | accessdate = 2008-01-04 }}</ref> A [[pink ribbon]] is worn to recognize the struggle that sufferers face when battling the cancer.<ref>{{cite web | title = Pink Ribbon | url = http://pinkribbon.com/ | accessdate = 2008-01-04 }}</ref> [[Pink for October]] is an initiative started by Matthew Oliphant, which asks that any sites willing to help make people aware of breast cancer, change their template or layout to include the color pink, so that when visitors view the site, they see that the majority of the site is pink. Then after reading a short amount of information about breast cancer, or being redirected to another site, they are aware of the disease itself.<ref>{{cite web | title = Pink for October | url = http://pinkforoctober.org/ | accessdate = 2008-01-04 }}</ref> The patron saint of breast cancer is [[Saint Agatha]] of Sicily.<ref>{{cite web | title = Index of Saints | work = Catholic Forum | url = http://www.catholic-forum.com/saints/sainta04.htm | accessdate = 2008-01-04 }}</ref> ==Gallery== <gallery> Image:Breast self exam 1.jpg|Breast self exam Image:En Breast cancer illustrations.gif|Illustration of the early warning signs of breast cancer (click for larger image) Image:Mammogram.jpg|Woman undergoing [[mammogram]] Image:Mammo breast cancer.jpg|Mammography pictures, normal (left) and cancerous (right) Image:Mammogram showing breast cancer.jpg|Mammogram displaying breast cancer, indicated with an arrow (click for larger view) Image:Mastectomie 02.jpg|[[Mastectomy]] patient Image:Discrene Breast forms.JPG|[[Breast prostheses]] used by some mastectomy patients Image:Inflammatory breast cancer.jpg|Drawing of [[inflammatory breast cancer]] Image:RecurrentbreastCA.gif|Patient with advanced local-regional recurrence of breast cancer with an ulcerating axillary mass Image:BreastCancer.jpg|[[Mastectomy]] specimen containing a very large cancer of the breast (in this case, an invasive ductal carcinoma) Image:Breast cancer gross appearance.jpg|Typical macroscopic ([[gross examination|gross]]) appearance of the cut surface of a [[mastectomy]] specimen containing a cancer, in this case, an invasive ductal carcinoma of the breast, pale area at the center Image:Breast cancer.JPG|Excised human breast tissue, showing a stellate area of cancer 2cm in diameter. The lesion could be felt clinically as a hard mobile lump, not attached to skin or chest wall. Image:Granular Cell Tumor.jpg|Benign granular cell tumor removed from a woman's breast. Granular cell tumors of the breast represent one of the few lesions that can impersonate an invasive breast cancer on gross examination. Image:Infiltrating ductal carcinoma of the breast.jpg|Infiltrating ductal carcinoma of the breast Image:Muc1.jpg|Infiltrating ductal carcinoma of the Breast assayed with anti Mucin 1 antibody Image:HER2(2).jpg|Breast cancer (Infiltrating ductal carcinoma of the breast) assayed with anti HER-2 (ErbB2) antibody Image:Breast invasive lobular carcinoma (2).jpg|Invasive lobular carcinoma of the breast demonstrating a predominantly lobular growth pattern Image:Tripolar Mitosis - breast carcinoma.jpg|Metaplastic (sarcomatoid) carcinoma of the breast. Image:Breast DCIS histopathology (1).jpg|Histopathologic image from ductal cell carcinoma in situ (DCIS) of breast. Hematoxylin-eosin stain. Image:Breast invasive scirrhous carcinoma histopathology (1).jpg|Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. Hematoxylin and eosin stain. Image:Breast invasive scirrhous carcinoma histopathology (2) HER2 expression.JPG|Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. HER-2/neu oncoprotein expression by Ventana immunostaining system. Image:IDC1.jpg|Breast cancer (Infiltrating ductal carcinoma of the breast) dyed with H&E Image:Intraductal papilloma histopathology (1).jpg|Histopathology of intraductal papilloma of the breast by excisional biopsy. Hematoxylin and eosin stain. Image:Intraductal papilloma histopathology (2) smooth muscle actin.JPG|Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for alpha-smooth muscle actin. Image:Intraductal papilloma histopathology (3) p63.JPG|Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for p63 protein. Image:Breast fibroadenoma by fine needle aspiration (1) DG stain.jpg|Breast fibroadenoma Image:Breast fibroadenoma by fine needle aspiration (2) PAP stain.jpg|Breast fibroadenoma Image:Breast fibradenoma (1).jpg|Histopathologic image of breast fibroadenoma. Core needle biopsy. Hematoxylin & eosin stain. Image:Breast fibradenoma (2).jpg|Histopathologic image of breast fibroadenoma. Core needle biopsy. Hematoxylin & eosin stain. Image:Intraductal papilloma histopathology (1).jpg|Histopathology of intraductal papilloma of the breast by excisional biopsy. Hematoxylin and eosin stain. Image:Intraductal papilloma histopathology (2) smooth muscle actin.JPG|Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for alpha-smooth muscle actin. Image:Intraductal papilloma histopathology (3) p63.JPG|Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for p63 protein. </gallery> == See also == <div style="-moz-column-count:2; column-count:2;"> *[[List of notable breast cancer patients according to occupation]] *[[List of notable breast cancer patients according to survival status]] *[[List of breast carcinogenic substances]] *[[Mammary tumor]] for breast cancer in other animals *[[Breast reconstruction]] *[[Alcohol and cancer]] *[[Mammography Quality Standards Act]] *[[National Breast Cancer Coalition]] *[[National Comprehensive Cancer Network]] *[[Breast Cancer Action]] *[[Breakthrough Breast Cancer]] *[[Barron Lerner]] (Physician) *[[International Agency for Research on Cancer]] *[[The Hormone Foundation]] *[[Susan G. Komen for the Cure]] </div> ==References== <!-- --------------------------------------------------------------- See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a discussion of different citation methods and how to generate footnotes using the <ref> & </ref> tags and the {{Reflist}} template -------------------------------------------------------------------- --> {{reflist|2}} {{refbegin}} <!-- add references here --> * {{cite web|url=http://www.abortion.org.au/breastcancer.htm |title=Abortion and Breast Cancer — A Forged Link |accessdate=2007-11-03 |last=Arthur |first=Joyce |date=2002-03 |publisher=[[The Humanist]] }} * {{cite web|url=http://www.sesiahs.health.nsw.gov.au/publications/cancerControl/26%20Alcohol.PDF |title=Information for GPs – Alcohol and cancer risk |accessdate=2007-11-03 |last=Ressler |first=Kelly-Anne |date=2002-08 |format=PDF |work=Cancer Control Program |publisher=South Eastern Sydney and Illawarra Area Health Service }} * {{cite web|url=http://www.center4research.org/pdf/booklet04bc.pdf |title=Surgery choices for women with early-stage Breast cancer |accessdate=2007-11-03 |format=PDF |work=National Cancer Institute |publisher=[[United States Department of Health and Human Services]] }} * {{cite web|url=http://envirocancer.cornell.edu/FactSheet/Diet/fs13.alcohol.cfm |title=Alcohol and the Risk of Breast Cancer |accessdate=2007-11-03 |last=Napieralski |first=Julie A. |coauthors=Carol Devine |date=1988-03 |work=Program on Breast Cancer and Environmental Risk Factors in New York State |publisher=[[Cornell University]] }} * {{cite web|url=http://www.nationmaster.com/graph/hea_bre_can_inc-health-breast-cancer-incidence |title= Breast cancer incidence (most recent) by country |accessdate=2007-11-03 |publisher=[[NationMaster.com]] }} * {{cite web|url=http://www.radiologyinfo.org/en/info.cfm?pg=breastcancer&bhcp=1 |title=Radiology Info - Breast Cancer |accessdate=2007-11-03 |work=Radiological Society of North America |publisher=[[Radiological Society of North America]] }} * {{cite web|url=http://www.center4research.org/bc071502.html |title=Mastectomy v. Lumpectomy: Who Decides? |accessdate=2007-11-03 |last=Zuckerman |first=Diana |work=National Research Center for Women & Families |publisher=[[National Research Center]] }} {{refend}} ==External links== {{Commons|Category:Breast cancer|Breast cancer}} {{Wikibooks|Sexual Health|Cancer#Breast Cancer}} * {{dmoz|/Health/Conditions_and_Diseases/Cancer/Breast/}} * {{Yahoo directory|Health/Diseases_and_Conditions/Breast_Cancer/|Breast cancer}} * {{Wiktionary-inline|breast cancer|Breast cancer}} <!--===========================({{NoMoreLinks}})=============================== | DO NOT ADD MORE LINKS TO THIS ARTICLE. WIKIPEDIA IS NOT A COLLECTION OF | | LINKS. 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