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==[[Breast cancer classification|Classification]]==
==[[Breast cancer classification|Classification]]==
[[Breast cancer classification#Major Scheme|Major Scheme]] | [[Breast cancer classification#Staging|Staging]] | [[Breast cancer classification#Pathologic Types|Pathologic Types]] | [[Breast cancer classification#Histologic Types|Histologic Types]]
[[Breast cancer classification#Major Scheme|Major Scheme]] | [[Breast cancer classification#Staging|Staging]] | [[Breast cancer classification#Pathologic Types|Pathologic Types]] | [[Breast cancer classification#Histologic Types|Histologic Types]]
===Clinical categorizations===
Breast cancer is occasionally classified clinically (on [[physical exam]] findings, [[medical history|(medical) history]]). [[Inflammatory breast cancer]] (IBC) is an example of a clinically classified breast cancer and can be any histologic type.<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>
==Signs and symptoms==
Early breast cancer can in some cases present as breast pain ([[mastodynia]]) or a painful lump.  Since the advent of breast mammography, breast cancer is most frequently discovered as an asymptomatic nodule on a mammogram, before any symptoms are present.  A lump under the arm or above the [[collarbone]] that does not go away may be present. When breast cancer associates with skin [[inflammation]], this is known as inflammatory breast cancer.  In inflammatory breast cancer, the breast tumor itself is causing an [[inflammatory]] reaction of the skin, and this can cause pain, swelling, warmth, and redness throughout the breast.
Changes in the appearance or shape of the breast can raise suspicions of breast cancer.
Another reported symptom complex of breast cancer is [[Paget's disease of the breast]].  This [[syndrome]] presents as eczematoid skin changes at the nipple, and is a late manifestation of an underlying breast cancer.
Most breast symptoms do not turn out to represent underlying breast cancer.  Benign breast diseases such as fibrocystic mastopathy], [[mastitis]], functional mastodynia, and [[fibroadenoma]] of the breast are more common causes of breast symptoms.  The appearance of a new breast symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.
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.  Pleural effusions are not uncommon with [[metastatic]] breast cancer.  Obviously, these symptoms are "non-specific," meaning they can also be manifestations of many other illnesses.


==Epidemiology and etiology==
==Epidemiology and etiology==
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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/cmn_who_indrisk.html | 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 |id=PMID 16421368}}</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> 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 and radiation.<ref name="acs bc facts 2005-6">{{cite web |author=[[American Cancer Society|ACS]] |year=2005 |title=Breast Cancer Facts & Figures 2005-2006 |url=http://www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf |accessdate=2007-04-26}}</ref>
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/cmn_who_indrisk.html | 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 |id=PMID 16421368}}</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> 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 and radiation.<ref name="acs bc facts 2005-6">{{cite web |author=[[American Cancer Society|ACS]] |year=2005 |title=Breast Cancer Facts & Figures 2005-2006 |url=http://www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf |accessdate=2007-04-26}}</ref>


== Prevention ==
==Signs and symptoms==
=== Phytoestrogens and soy ===
Early breast cancer can in some cases present as breast pain ([[mastodynia]]) or a painful lumpSince the advent of breast mammography, breast cancer is most frequently discovered as an asymptomatic nodule on a mammogram, before any symptoms are present.  A lump under the arm or above the [[collarbone]] that does not go away may be present. When breast cancer associates with skin [[inflammation]], this is known as inflammatory breast cancer. In inflammatory breast cancer, the breast tumor itself is causing an [[inflammatory]] reaction of the skin, and this can cause pain, swelling, warmth, and redness throughout the breast.
[[Phytoestrogens]] such as found in soybeans have been extensively studied in animal and human ''in-vitro'' and epidemiological studiesThe 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>Gikas PD, Mokbel K. (2005[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16526415&query_hl=5&itool=pubmed_docsum Phytoestrogens and the risk of breast cancer: a review of the literature]. Int J Fertil Women's Med.</ref> 
It seems reasonable to conclude that [[soybean]]-based [[phytoestrogens]] are not a major contributor to the incidence of breast cancer.


=== Folic acid (folate) ===
Changes in the appearance or shape of the breast can raise suspicions of breast cancer.
{{main|Folic acid}}
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/act/alcoholandhealth/issues/issue_may04/html/04-0506-ellison_baily.html ''Folate, Alcohol, and Cancer Risk'']</ref><ref>Bailey, L.B. Folate, methyl-related nutrients, alcohol and the MTHFR 677C -> T polymorphous affect cancer risk: intake recommendations. Journal of Nutrition, 2003, 133, 37485-37535</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}}</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 | id=PMID 8569555}}</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  | id=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  | id=PMID 1917236}}</ref>
Another reported symptom complex of breast cancer is [[Paget's disease of the breast]].  This [[syndrome]] presents as eczematoid skin changes at the nipple, and is a late manifestation of an underlying breast cancer.


Foods rich in folate include citrus fruits, citrus juices, dark green leafy vegetables (such as spinach), dried beans, and peas. Vitamin B9 can also be taken in a multivitamin pill.
Most breast symptoms do not turn out to represent underlying breast cancer.  Benign breast diseases such as fibrocystic mastopathy], [[mastitis]], functional mastodynia, and [[fibroadenoma]] of the breast are more common causes of breast symptoms. The appearance of a new breast symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.


===Oophorectomy and mastectomy===
Occasionally, breast cancer presents as [[metastatic]] disease, that is, cancer that has spread beyond the original organMetastatic 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. Pleural effusions are not uncommon with [[metastatic]] breast cancer. Obviously, these symptoms are "non-specific," meaning they can also be manifestations of many other illnesses.
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}}</ref>
 
Bilateral prophylactic [[Mastectomy|mastectomies]] have been shown to prevent breast cancer in high-risk individuals, such as patients with [[BRCA1]] or [[BRCA2]] gene mutations.
 
===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><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 were based on studies of [[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=}}</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 cancer]]s 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=}}</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, Steven Galson, director, US Food and Drug Administration's [[Center for Drug Evaluation and Research]] announced approval of the sale of raloxifene 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>


==[[Breast cancer screening|Screening]]==
==[[Breast cancer screening|Screening]]==
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==Diagnosis==
==Diagnosis==
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.
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==
==Staging==
Breast cancer is [[Cancer staging|staged]] according to the TNM system, updated in the American Joint Committee on Cancer (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.
Breast cancer is [[Cancer staging|staged]] according to the TNM system, updated in the American Joint Committee on Cancer (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.


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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://newsmax.com/archives/articles/2007/2/6/130740.shtml FDA Approves New Breast Cancer Test]". Associated Press, February 6, 2007.</ref>
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://newsmax.com/archives/articles/2007/2/6/130740.shtml FDA Approves New Breast Cancer Test]". Associated Press, February 6, 2007.</ref>
==[[Breast cancer primary prevention|Primary Prevention]]==
[[Breast cancer primary prevention#Phytoestrogens and soy|Phytoestrogens and soy]] | [[Breast cancer primary prevention#Folic acid (folate)|Folic acid (folate)]] | [[Breast cancer primary prevention#Oophorectomy and mastectomy|Oophorectomy and mastectomy]] |[[Breast cancer primary prevention#Medications|Medications]]


==Prognosis==
==Prognosis==
There are several prognostic factors associated with breast cancer. [[Cancer staging|Stage]] is the most important, as it takes into consideration local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. Breast cancer patients whose lymph nodes are cancer-free have a much better prognosis than those whose lymph nodes are positive for cancer.   
There are several prognostic factors associated with breast cancer. [[Cancer staging|Stage]] is the most important, as it takes into consideration local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. Breast cancer patients whose lymph nodes are cancer-free have a much better prognosis than those whose lymph nodes are positive for cancer.   


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==Cultural references==
==Cultural references==
[[Image:Pink ribbon.svg| 80px | right]]
[[Image:Pink ribbon.svg| 80px | right]]
In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease. A pink ribbon is worn to recognize the struggle that sufferers face when battling the cancer.
In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease. A pink ribbon is worn to recognize the struggle that sufferers face when battling the cancer.

Revision as of 16:28, 29 November 2011

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ICD-10 C50
ICD-9 174-175
OMIM 114480
DiseasesDB 1598
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor(s)-In-Chief: Jack Khouri

Overview

Classification

Major Scheme | Staging | Pathologic Types | Histologic Types

Epidemiology and etiology

Epidemiological risk factors for a disease can provide important clues as to the etiology of a disease. The first work 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.

Today, breast cancer, like other forms of cancer, is considered to be the final outcome of multiple environmental and hereditary factors.

  1. Lesions to DNA such as genetic mutations. Exposure to estrogen has been experimentally linked to the mutations that cause breast cancer.[1] Beyond the contribution of estrogen, research has implicated viral oncogenesis and the contribution of ionizing radiation.
  2. Failure of immune surveillance, which usually removes malignancies at early phases of their natural history.
  3. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells, for example in the angiogenesis necessary to promote new blood vessel growth near new cancers.
  4. Inherited defects in DNA repair genes, such as BRCA1, BRCA2 and p53.

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. Approximately 5% of new breast cancers are attributable to hereditary syndromes, while no etiology is known for the other 95% of cases.[2]

The primary risk factors that have been identified are sex,[3] age,[4] childbearing, hormones,[5] a high-fat diet,[6] alcohol intake,[7] obesity,[8] and environmental factors such as tobacco use and radiation.[9]

Signs and symptoms

Early breast cancer can in some cases present as breast pain (mastodynia) or a painful lump. Since the advent of breast mammography, breast cancer is most frequently discovered as an asymptomatic nodule on a mammogram, before any symptoms are present. A lump under the arm or above the collarbone that does not go away may be present. When breast cancer associates with skin inflammation, this is known as inflammatory breast cancer. In inflammatory breast cancer, the breast tumor itself is causing an inflammatory reaction of the skin, and this can cause pain, swelling, warmth, and redness throughout the breast.

Changes in the appearance or shape of the breast can raise suspicions of breast cancer.

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes at the nipple, and is a late manifestation of an underlying breast cancer.

Most breast symptoms do not turn out to represent underlying breast cancer. Benign breast diseases such as fibrocystic mastopathy], mastitis, functional mastodynia, and fibroadenoma of the breast are more common causes of breast symptoms. The appearance of a new breast symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.

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. Pleural effusions are not uncommon with metastatic breast cancer. Obviously, these symptoms are "non-specific," meaning they can also be manifestations of many other illnesses.

Screening

X Ray Mammography | Breast MRI | Breast Ultrasound | Self Exam | Genetic Testing

Diagnosis

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 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

Breast cancer is staged according to the TNM system, updated in the American Joint Committee on Cancer (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.

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)

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+).[10] Receptor status modifies the treatment as, for instance, only ER-positive tumors, not ER-negative tumors, are sensitive to hormonal therapy.

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.[11]

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.[12]

Primary Prevention

Phytoestrogens and soy | Folic acid (folate) | Oophorectomy and mastectomy |Medications

Prognosis

There are several prognostic factors associated with breast cancer. Stage is the most important, as it takes into consideration local involvement, lymph node status and whether metastatic disease is present. The higher the stage at diagnosis, the worse the prognosis. Breast cancer patients whose lymph nodes are cancer-free have a much better prognosis than those whose lymph nodes are positive for cancer.

The presence of estrogen and progesterone receptors in the cancer cell is another important prognostic factor which may guide treatment. Hormone receptor positive breast cancer is usually associated with much better prognosis compared to hormone negative breast cancer.

HER2/neu status has also been described as a prognostic factor. 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 groups 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.

Metastasis

Most people understand breast cancer as something that happens in the breast. However it can metastasise (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 — either axillary clearance, sampling, or sentinel node biopsy.

Breast cancer can also spread to other parts of the body via blood vessels. So it can spread to the lungs, pleura (the lining of the lungs), liver, brain, and most commonly to the bones. 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 why they complain about 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, the doctor often treats the patient with medicines that lower her estrogen levels.

History

Breast cancer may be one of the oldest known forms of cancer tumors in humans. The oldest description of cancer (although the term cancer was not used) 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."[13] 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 mastectomies in 1882. He became known for his Halsted radical mastectomy, a surgical procedure that remained popular up to the 1970s.

Cultural references

In the month of October, breast cancer is recognized by survivors, family and friends of survivors and/or victims of the disease. A pink ribbon is worn to recognize the struggle that sufferers face when battling the cancer.

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.

The patron saint of breast cancer is Saint Agatha of Sicily.

Related Chapters

References

  1. Cavalieri E, Chakravarti D, Guttenplan J; et al. (2006). "Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention". Biochim. Biophys. Acta. 1766 (1): 63–78. doi:10.1016/j.bbcan.2006.03.001. PMID 16675129.
  2. Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN (1995). "Proportion of breast cancer cases in the United States explained by well-established risk factors". J. Natl. Cancer Inst. 87 (22): 1681–5. PMID 7473816. |access-date= requires |url= (help)
  3. Giordano, Sharon H (May 2004). "Breast carcinoma in men". Cancer. American Cancer Society. 101 (1): 51–57. Unknown parameter |coauthors= ignored (help)
  4. "Individual Risk Factors". BreastCancer.org. Retrieved 2007-03-11.
  5. Yager JD (2006). "Estrogen carcinogenesis in breast cancer". New Engl J Med. 354 (3): 270–82. PMID 16421368. Unknown parameter |coauthors= ignored (help)
  6. Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK; et al. "Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study (WINS)". J Natl Cancer Inst. 98 (24): 1767–1776. PMID 17179478.
  7. Boffetta, Paolo (2006-03-23). "The burden of cancer attributable to alcohol drinking". International Journal of Cancer. Wiley-Liss, Inc. 119 (4): 884–887. doi:10.1002/ijc.21903. PMID 16557583. Retrieved 2006-10-09. Unknown parameter |coauthors= ignored (help)
  8. BBC report Weight link to breast cancer risk
  9. ACS (2005). "Breast Cancer Facts & Figures 2005-2006" (PDF). Retrieved 2007-04-26.
  10. Rusiecki JA, Holford TR, Zahm SH, Zheng T. Breast cancer risk factors according to joint estrogen receptor and progesterone receptor status. Cancer Detect Prev 2005;29:419-26
  11. accessed 1/30/07 cancer.gov
  12. "FDA Approves New Breast Cancer Test". Associated Press, February 6, 2007.
  13. "The History of Cancer". American Cancer Society. 2002-03-25. Retrieved 2006-10-09.

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