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{{Breast cancer}}
{{CMG}}; '''Assistant Editor(s)-In-Chief:''' [[User:Jack Khouri|Jack Khouri]]
{{CMG}}; {{AE}} {{Soroush}} {{Ammu}}
==Overview==
Breast cancer was first described in Egyptian literature. In 1976, mammography became officially recommended by the [[American cancer society]] for screening breast cancer. Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. Genes involved in the pathogenesis of breast cancer include  ''BRCA1'', ''BRCA2'' and ''p53''. On microscopic histopathological analysis, minimal tubule formation marked pleomorphism, and numerous mitotic figures are characteristic findings of breast cancer. Breast cancer must be differentiated from other diseases that cause mass in the breast such as [[fibroadenoma]], [[fibrocystic disease of the breast]], [[mastitis]], [[galactocele]], [[traumatic fat necrosis]], [[intraductal papilloma]], and [[lipoma]]. The prevalence of breast cancer is approximately 124.8 per 100,000 women per year. The number of deaths was 21.9 per 100,000 women per year, based on 2010-2012 data. Common risk factors in the development of breast cancer are family history, dense breast, obesity, radiation therapy, older age at first birth or never having given birth, hormone replacement therapy, and alcohol. Symptoms of breast cancer include a lump in the breast, discharge from the nipple, and thickening of the skin. A breast biopsy may be helpful in the diagnosis of breast cancer. Breast cancer chemotherapy refers to the use of [[cytotoxicity|cytotoxic]] [[drug]]s ([[chemotherapy]]) in the treatment of [[breast cancer]]. The aim of chemotherapy is to prevent the growth of micrometastatic disease that is responsible for systemic disease recurrence. Surgery is the mainstay of treatment for breast cancer.
 
==Historical Perspective==
Breast cancer was first described in Egyptian literature. In 1976, [[mammography]] became officially recommended by the American cancer society for [[Screening (medicine)|screening]] the [[breast]] [[Cancer|cance]]<nowiki/>r.
 
==Classification==
Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. There are also other methods of classification such as classification based on gene expression, and classification based on hormone receptors present. In practice, a combination of all above-mentioned classification is combined with the surgical characteristics of tumors and radiologic findings is being applied for patient management, treatment planning, and prognosis determination.
 
==Pathophysiology==
Genes involved in the pathogenesis of breast cancer include ''[[BRCA1]]'', ''[[BRCA2]]'' and ''[[p53]]''. On microscopic [[Histopathology|histopathologi]]<nowiki/>cal analysis, minimal tubule formation, marked [[pleomorphism]], and numerous [[Mitosis|mitotic figures]] are characteristic findings of breast cancer.


==Overview==
==Causes==
'''Breast cancer''' is a [[cancer]] of the glandular [[breast]] tissue.
The cause of breast cancer is not yet known exactly, though many risk factors can increase the chance of developing breast cancer.
 
==Differentiating Epithelioid sarcoma from other Diseases==
Breast cancer must be differentiated from other diseases such as [[malignancy]], [[cysts]], [[inflammation]] and non-inflammatory solid lumps. Breast symptoms such as [[nipple discharge]] and [[mastalgia]] require assessment as well. Differentiating breast cancer different types of breast lumps are based on imaging findings and breast clinical exam results.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
Worldwide, breast cancer is the fifth most common cause of cancer death (after [[lung cancer]], [[stomach cancer]], [[liver cancer]], and [[colon cancer]]).<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> In 2005, breast cancer caused 502,000 deaths (7% of cancer deaths; almost 1% of all deaths) worldwide.<ref name="who fact sheet" /> Among women worldwide, breast cancer is the most common cause of death due to cancer.<ref name="who fact sheet" />
The prevalence of breast cancer is approximately 124.8 per 100,000 women per year. The number of deaths was 21.9 per 100,000 women per year, based on 2010-2012 data. About 1 out of 8 women in United states will develop invasive [[breast]] cancer. Annually (i . e in 2019) around 268,600 and 62,930 new cases of invasive and non-invasive (in situ) breast cancer are expected to be diagnosed respectively. In men, life time likelihood of developing breast cancer is about 1 in 883. Annually 2,670 new cases of invasive breast cancer are expected to be diagnosed in males. Breast cancer increasing pattern of [[incidence]] rates began decreasing after year 2000 in US.
 
==Risk Factors==
Common risk factors in the development of breast cancer are family history, dense breast, obesity, radiation therapy, older age at first birth or never having given birth, hormone replacement therapy, and alcohol.
 
==Screening==
According to the U.S. Preventive Service Task Force (USPSTF), screening for breast cancer by a mammogram is recommended for women aged 50-74 years, twice a year.
 
==Natural history, Complications and Prognosis==
If left untreated, 22% of patients with breast cancer may regress. Common complications of breast cancer include metastasis. Prognosis is generally good with treatment.
 
Breast cancer used to be [[Cancer staging|staged]] according to the TNM system. Recently, the American Joint Committee on Cancer (AJCC) Staging Manual (8th edition, last updated 1/25/2018) extensively revised their staging system. The 8th edition of the AJCC TNM breast cancer staging system delivers a flexible platform for prognostic classification based on traditional anatomic factors, which may be modified and enhanced with respect to patient biomarkers and other prognostic panel data. Nevertheless, in order to maintain worldwide value, AJCC tumor staging system remained based on classic TNM anatomic factors. 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.
 
==Diagnostic study of choice==
 
Biopsy is the gold standard test for the diagnosis of breast cancer. Meanwhile, the diagnostic study of choice for breast cancer screening is mammography. [[Magnetic resonance imaging]] ([[Magnetic resonance imaging|MRI]]) is also recommended in selected patients. Compared to the [[Mammography|Mammography,]] [[Magnetic resonance imaging|MRI]]<nowiki/>has higher [[Sensitivity (tests)|sensitivity]] and lower [[Specificity (tests)|specificity]].
 
==Biopsy==
Breast [[biopsy]] the only definite way to [[Diagnosis|diagnose]] breast cancer. Hence, every patient with a suspicious [[Breast lumps|lesion in her/his breast]] needs a [[biopsy]] to evaluate the nature of the mass precisely. Nevertheless, a large number of [[biopsy]] samples taken from [[breast lumps]] are found to be [[benign]].
 
==History and Symptoms==
Symptoms of breast cancer include a lump in the breast, discharge from the nipple, and thickening of the skin.
 
==Physical Examination==
Patients with breast cancer usually are generally well appearing. Physical examination of patients with breast cancer is usually remarkable for a lump in the breast, peau d'orange, an inverted nipple.
 
==Laboratory Findings==
Laboratory studies play a crucial role in [[Prevention (medical)|prevention]], [[diagnosis]], [[Cancer staging|staging]], [[Treatment Planning|treatment planning]], management, determining [[prognosis]] and follow up of patients with breast cancer. Among them are single gene studies (i. e. [[BRCA1]], [[BRCA2]], and [[HER2]]), multiple gene panels (i.e. Oncotype DX), [[Tumor marker|tumor markers]] (Ki67), and metastatic markers such as serum [[alkaline phosphatase]] as a marker of [[bone metastasis]]. A variety of other blood chemistry tests are also used in the management process of patients with breast cancer, among them are [[liver function tests]] ([[Alanine transaminase|alanine aminotransferase]] ([[Alanine transaminase|ALT]]), [[aspartate transaminase]] ([[Aspartate transaminase|AST]]) , [[bilirubin]], [[alkaline phosphatase]]) and markers of kidney function ([[Blood urea nitrogen|BUN]], [[creatinine]]).
 
== Electrocardiogram ==
There are no ECG findings associated with breast cancer
 
== X Ray ==
There are no x-ray findings associated with breast cancer. However, an x-ray may be helpful in the diagnosis of complications of breast cancer, which include:
 
* Bone and lung metastasis.
* Nevertheless, more accurate and sensitive imaging techniques are available and are widely used, among them are [[Computed tomography|CT scan]], [[Magnetic resonance imaging|MRI]], [[Positron emission tomography|PET scan]], PET- CT scan.
 
== CT scan ==
There are no CT scan findings associated with breast cancer. However, a CT scan may be helpful in staging and the diagnosis of complications of breast cancer, which include [[Metastasis|brain, bone, liver, lung, and peritoneal metastasis]]. A combination of CT scan with other imaging techniques such as PET scan increases its
 
==MRI==
Although a number of breast MRI indications remained controversial, breast MRI has been recommended for a variety of conditions such as studying a probable occult primary breast cancers, evaluation of disease extension, watching up the response to neoadjuvant chemotherapy, studying disease recurrence, as an adjuvant method to clarify inconclusive clinical or imaging findings, and as the recommended method of screening for high-risk patients another indication of breast MRI is assessment of silicone implant integrity
 
==Ultrasound==
Breast ultrasound may be helpful in the diagnosis of breast [[cancer]], especially, to further evaluate an abnormal mammogram and to distinguish between solid and cystic lesions. [[Medical ultrasonography|Ultrasonography]] is the first-line imaging method in pregnant women and women less than 30 years old with focal breast sign and symptoms. Although[[Medical ultrasonography|Ultrasonography]] might be used as an adjunct to [[mammography]] in women with increased breast density, it has not been shown to decrease mortality from breast cancer. Nevertheless, using ultrasound may increase the risk for false-positive findings, unnecessary breast biopsy, and follow-up imaging.


In the United States, breast cancer is the third most common cause of cancer death (after lung cancer and colon cancer). In 2007, breast cancer caused approximately 40,910 deaths (7% of cancer deaths; almost 2% of all deaths) in the U.S.<!--
It has been shown that heart failure is prevalent in women being treated with this novel treatment. As a potentially serious side effect of this novel treatment, serial [[Echocardiography]] is recommended in all patients treated with [[trastuzumab]].
  --><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>
Among women in the U.S., breast cancer is the most common form of cancer and the second- most common cause of cancer death (after lung cancer).<ref name="acs cancer facts 2007" /> Women in the U.S. have a 1 in 8 lifetime chance of developing invasive breast cancer and a 1 in 33 chance of breast cancer causing their death.<!--
  --><ref name="acs bc key stats">{{cite web |author=[[American Cancer Society]] |month=September 18, |year=2006 |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=2007-04-26}}</ref> A U.S. 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 amongst 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>


The number of cases has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world.<ref name="indy">{{cite news
==Other Imaging Studies==
  | last = Laurance
Other diagnostic studies for breast cancer include modified [[Magnetic resonance imaging|MRI]] utilities (high-field strength MRI, magnetic resonance [[spectroscopy]], and diffusion weighted imaging, breast-specific [[Nuclear medicine|gamma imaging]], [[Positron emission tomography|positron emission]]<nowiki/>mammography, scintimammography, [[Thermography (Sympathetic galvonic skin studies)|thermography]] and bone scan.
  | first = Jeremy
  | title =  Breast cancer cases rise 80% since Seventies
  | work = [[The Independent]]
  | date = 2006-09-29
  | url = http://news.independent.co.uk/uk/health_medical/article1771835.ece
  | 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> Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males, although it is less common.<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>


[[Epidemiological]] risk factors for a disease can provide important clues regarding 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. Some of the effects of environmental and hereditary factors that ultimately cause breast cancer are:
==Mammography==
# Lesions to [[DNA]] such as [[genetic mutations]]. Exposure to estrogen has been experimentally linked to the mutations that cause breast cancer.<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]].
Mammography has been proven to reduce mortality from [[breast cancer]]. No other imaging technique has been shown to reduce risk. In some countries, routine (annual to five-yearly) mammography of older women is encouraged as a screening method to diagnose early breast cancer.
# Failure of immune surveillance, which usually removes malignancies at early phases of their natural history.
# 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.
# Inherited defects in [[DNA repair genes]], such as ''BRCA1'', ''BRCA2'' and ''p53''.


Although many epidemiological risk factors have been identified, the specific cause of any individual breast cancer is often unknown.  In other words, epidemiological research is able to provide information regarding 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.<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 = | accessdate = 2007-05-26}}</ref>
==Other Diagnostic Studies==
Other diagnostic studies for breast cancer is hormone receptor testing.  


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>
==Medical Therapy==
Breast cancer chemotherapy is a combination of [[Cytotoxicity|cytotoxic]] [[Drug|drugs]] ([[chemotherapy]]), hormonal therapy, hormonal receptor modulators, aromatase inhibitors, monoclonal antibodies, and growth factor receptor tyrosine kinase inhibitors


==Diagnosis==
==Surgery==
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.
Surgery is the mainstay of treatment for breast cancer.


==Treatment==
==Bone Metastasis==
The mainstay of breast cancer treatment is [[surgery]] during which 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.
Bone is the most common site of [[breast cancer]] distant spread. Bone [[metastases]] due to the breast cancer cause major morbidity, decrease survival and reduce the quality of life of many patients. Rather than systemic chemotherapy, bisphosphonates like [[Pamidronate]], [[Alendronate]], [[Ibandronate]], [[Risedronate]], and [[Zoledronic acid]] , RANKL-RANK inhibitors like [[Denosumab|Denosumab, also has been recommended and studied for the treatment of bone metastases.]].Additionally, [[External beam radiotherapy]] (EBRT) has been, and continues to be, the mainstay for the treatment of painful, uncomplicated bone metastases.


In planning treatment, doctors can also use PCR tests such as [[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>
==Primary Prevention==
Avoiding risk factors and increasing protective factors may help prevent cancer.


==Future or Investigational Therapies==
Medical investigational therapies are a wide range of new generations of [[targeted therapy]], [[cancer vaccine]]<nowiki/>s, oncolytic [[virotherapy]], [[gene therapy]], and [[immunotherapy]]. Novel surgical and radiation techniques are also under investigation. A new generation of [[Clinical trial|clinical trials]] (adaptive trials) are already being used in the war against breast cancer (i.e. I-SPY 2).
==References==
==References==
{{reflist|2}}
{{reflist|2}}


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Latest revision as of 18:21, 4 October 2019

Breast Cancer Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Breast cancer from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic study of choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

CT scan

MRI

Echocardiography or Ultrasound

Other Imaging Studies

Other Diagnostic Studies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2] Ammu Susheela, M.D. [3]

Overview

Breast cancer was first described in Egyptian literature. In 1976, mammography became officially recommended by the American cancer society for screening breast cancer. Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. Genes involved in the pathogenesis of breast cancer include BRCA1, BRCA2 and p53. On microscopic histopathological analysis, minimal tubule formation marked pleomorphism, and numerous mitotic figures are characteristic findings of breast cancer. Breast cancer must be differentiated from other diseases that cause mass in the breast such as fibroadenoma, fibrocystic disease of the breast, mastitis, galactocele, traumatic fat necrosis, intraductal papilloma, and lipoma. The prevalence of breast cancer is approximately 124.8 per 100,000 women per year. The number of deaths was 21.9 per 100,000 women per year, based on 2010-2012 data. Common risk factors in the development of breast cancer are family history, dense breast, obesity, radiation therapy, older age at first birth or never having given birth, hormone replacement therapy, and alcohol. Symptoms of breast cancer include a lump in the breast, discharge from the nipple, and thickening of the skin. A breast biopsy may be helpful in the diagnosis of breast cancer. Breast cancer chemotherapy refers to the use of cytotoxic drugs (chemotherapy) in the treatment of breast cancer. The aim of chemotherapy is to prevent the growth of micrometastatic disease that is responsible for systemic disease recurrence. Surgery is the mainstay of treatment for breast cancer.

Historical Perspective

Breast cancer was first described in Egyptian literature. In 1976, mammography became officially recommended by the American cancer society for screening the breast cancer.

Classification

Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. There are also other methods of classification such as classification based on gene expression, and classification based on hormone receptors present. In practice, a combination of all above-mentioned classification is combined with the surgical characteristics of tumors and radiologic findings is being applied for patient management, treatment planning, and prognosis determination.

Pathophysiology

Genes involved in the pathogenesis of breast cancer include BRCA1, BRCA2 and p53. On microscopic histopathological analysis, minimal tubule formation, marked pleomorphism, and numerous mitotic figures are characteristic findings of breast cancer.

Causes

The cause of breast cancer is not yet known exactly, though many risk factors can increase the chance of developing breast cancer.

Differentiating Epithelioid sarcoma from other Diseases

Breast cancer must be differentiated from other diseases such as malignancy, cysts, inflammation and non-inflammatory solid lumps. Breast symptoms such as nipple discharge and mastalgia require assessment as well. Differentiating breast cancer different types of breast lumps are based on imaging findings and breast clinical exam results.

Epidemiology and Demographics

The prevalence of breast cancer is approximately 124.8 per 100,000 women per year. The number of deaths was 21.9 per 100,000 women per year, based on 2010-2012 data. About 1 out of 8 women in United states will develop invasive breast cancer. Annually (i . e in 2019) around 268,600 and 62,930 new cases of invasive and non-invasive (in situ) breast cancer are expected to be diagnosed respectively. In men, life time likelihood of developing breast cancer is about 1 in 883. Annually 2,670 new cases of invasive breast cancer are expected to be diagnosed in males. Breast cancer increasing pattern of incidence rates began decreasing after year 2000 in US.

Risk Factors

Common risk factors in the development of breast cancer are family history, dense breast, obesity, radiation therapy, older age at first birth or never having given birth, hormone replacement therapy, and alcohol.

Screening

According to the U.S. Preventive Service Task Force (USPSTF), screening for breast cancer by a mammogram is recommended for women aged 50-74 years, twice a year.

Natural history, Complications and Prognosis

If left untreated, 22% of patients with breast cancer may regress. Common complications of breast cancer include metastasis. Prognosis is generally good with treatment.

Breast cancer used to be staged according to the TNM system. Recently, the American Joint Committee on Cancer (AJCC) Staging Manual (8th edition, last updated 1/25/2018) extensively revised their staging system. The 8th edition of the AJCC TNM breast cancer staging system delivers a flexible platform for prognostic classification based on traditional anatomic factors, which may be modified and enhanced with respect to patient biomarkers and other prognostic panel data. Nevertheless, in order to maintain worldwide value, AJCC tumor staging system remained based on classic TNM anatomic factors. 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.

Diagnostic study of choice

Biopsy is the gold standard test for the diagnosis of breast cancer. Meanwhile, the diagnostic study of choice for breast cancer screening is mammography. Magnetic resonance imaging (MRI) is also recommended in selected patients. Compared to the Mammography, MRIhas higher sensitivity and lower specificity.

Biopsy

Breast biopsy the only definite way to diagnose breast cancer. Hence, every patient with a suspicious lesion in her/his breast needs a biopsy to evaluate the nature of the mass precisely. Nevertheless, a large number of biopsy samples taken from breast lumps are found to be benign.

History and Symptoms

Symptoms of breast cancer include a lump in the breast, discharge from the nipple, and thickening of the skin.

Physical Examination

Patients with breast cancer usually are generally well appearing. Physical examination of patients with breast cancer is usually remarkable for a lump in the breast, peau d'orange, an inverted nipple.

Laboratory Findings

Laboratory studies play a crucial role in prevention, diagnosis, staging, treatment planning, management, determining prognosis and follow up of patients with breast cancer. Among them are single gene studies (i. e. BRCA1, BRCA2, and HER2), multiple gene panels (i.e. Oncotype DX), tumor markers (Ki67), and metastatic markers such as serum alkaline phosphatase as a marker of bone metastasis. A variety of other blood chemistry tests are also used in the management process of patients with breast cancer, among them are liver function tests (alanine aminotransferase (ALT), aspartate transaminase (AST) , bilirubin, alkaline phosphatase) and markers of kidney function (BUN, creatinine).

Electrocardiogram

There are no ECG findings associated with breast cancer

X Ray

There are no x-ray findings associated with breast cancer. However, an x-ray may be helpful in the diagnosis of complications of breast cancer, which include:

  • Bone and lung metastasis.
  • Nevertheless, more accurate and sensitive imaging techniques are available and are widely used, among them are CT scan, MRI, PET scan, PET- CT scan.

CT scan

There are no CT scan findings associated with breast cancer. However, a CT scan may be helpful in staging and the diagnosis of complications of breast cancer, which include brain, bone, liver, lung, and peritoneal metastasis. A combination of CT scan with other imaging techniques such as PET scan increases its

MRI

Although a number of breast MRI indications remained controversial, breast MRI has been recommended for a variety of conditions such as studying a probable occult primary breast cancers, evaluation of disease extension, watching up the response to neoadjuvant chemotherapy, studying disease recurrence, as an adjuvant method to clarify inconclusive clinical or imaging findings, and as the recommended method of screening for high-risk patients another indication of breast MRI is assessment of silicone implant integrity

Ultrasound

Breast ultrasound may be helpful in the diagnosis of breast cancer, especially, to further evaluate an abnormal mammogram and to distinguish between solid and cystic lesions. Ultrasonography is the first-line imaging method in pregnant women and women less than 30 years old with focal breast sign and symptoms. AlthoughUltrasonography might be used as an adjunct to mammography in women with increased breast density, it has not been shown to decrease mortality from breast cancer. Nevertheless, using ultrasound may increase the risk for false-positive findings, unnecessary breast biopsy, and follow-up imaging.

It has been shown that heart failure is prevalent in women being treated with this novel treatment. As a potentially serious side effect of this novel treatment, serial Echocardiography is recommended in all patients treated with trastuzumab.

Other Imaging Studies

Other diagnostic studies for breast cancer include modified MRI utilities (high-field strength MRI, magnetic resonance spectroscopy, and diffusion weighted imaging, breast-specific gamma imaging, positron emissionmammography, scintimammography, thermography and bone scan.


Mammography

Mammography has been proven to reduce mortality from breast cancer. No other imaging technique has been shown to reduce risk. In some countries, routine (annual to five-yearly) mammography of older women is encouraged as a screening method to diagnose early breast cancer.

Other Diagnostic Studies

Other diagnostic studies for breast cancer is hormone receptor testing.

Medical Therapy

Breast cancer chemotherapy is a combination of cytotoxic drugs (chemotherapy), hormonal therapy, hormonal receptor modulators, aromatase inhibitors, monoclonal antibodies, and growth factor receptor tyrosine kinase inhibitors

Surgery

Surgery is the mainstay of treatment for breast cancer.

Bone Metastasis

Bone is the most common site of breast cancer distant spread. Bone metastases due to the breast cancer cause major morbidity, decrease survival and reduce the quality of life of many patients. Rather than systemic chemotherapy, bisphosphonates like Pamidronate, Alendronate, Ibandronate, Risedronate, and Zoledronic acid , RANKL-RANK inhibitors like Denosumab, also has been recommended and studied for the treatment of bone metastases..Additionally, External beam radiotherapy (EBRT) has been, and continues to be, the mainstay for the treatment of painful, uncomplicated bone metastases.

Primary Prevention

Avoiding risk factors and increasing protective factors may help prevent cancer.

Future or Investigational Therapies

Medical investigational therapies are a wide range of new generations of targeted therapy, cancer vaccines, oncolytic virotherapy, gene therapy, and immunotherapy. Novel surgical and radiation techniques are also under investigation. A new generation of clinical trials (adaptive trials) are already being used in the war against breast cancer (i.e. I-SPY 2).

References


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