Breast cancer pathophysiology: Difference between revisions
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Genes involved in the pathogenesis of breast cancer include ''BRCA1'', ''BRCA2'' and ''p53''. | Genes involved in the pathogenesis of breast cancer include ''BRCA1'', ''BRCA2'' and ''p53''. | ||
==Genetics== | ==Genetics== | ||
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: | * 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: | ||
# 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]]. | # 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]]. | ||
# Failure of immune surveillance, which usually removes malignancies at early phases of their natural history. | # Failure of immune surveillance, which usually removes malignancies at early phases of their natural history. | ||
| Line 13: | Line 13: | ||
[[Image:Breast cancer.png]] | [[Image:Breast cancer.png]] | ||
Breast cancer, like other [[cancers]], occurs because of an interaction between the environment and a defective gene. Normal cells divide as many times as needed and stop; they attach to other cells and stay in place in tissues. Cells become cancerous when mutations destroy their ability to stop dividing, to attach to other cells, and to stay where they belong. | * Breast cancer, like other [[cancers]], occurs because of an interaction between the environment and a defective gene. Normal cells divide as many times as needed and stop; they attach to other cells and stay in place in tissues. Cells become cancerous when mutations destroy their ability to stop dividing, to attach to other cells, and to stay where they belong. | ||
Normal cells will commit cell suicide ([[apoptosis]]) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the [[PI3K]]/[[AKT]] pathway; another one is the [[Ras (protein)|RAS]]/[[Mitogen-activated protein kinase kinase|MEK]]/[[Extracellular signal-regulated kinases|ERK]] pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the [[PTEN (gene)|PTEN]] protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.<ref>{{Cite conference | * Normal cells will commit cell suicide ([[apoptosis]]) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the [[PI3K]]/[[AKT]] pathway; another one is the [[Ras (protein)|RAS]]/[[Mitogen-activated protein kinase kinase|MEK]]/[[Extracellular signal-regulated kinases|ERK]] pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the [[PTEN (gene)|PTEN]] protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.<ref>{{Cite conference | ||
| coauthors = Adrian Lee, Carlos Arteaga | | coauthors = Adrian Lee, Carlos Arteaga | ||
| title = 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium | | title = 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium | ||
| Line 21: | Line 21: | ||
| date = Dec. 14, 2009 | | date = Dec. 14, 2009 | ||
| url = http://www.sabcs.org/Newsletter/Docs/SABCS_2009_Issue5.pdf}}</ref> | | url = http://www.sabcs.org/Newsletter/Docs/SABCS_2009_Issue5.pdf}}</ref> | ||
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 = Biochimica et Biophysica Acta | volume = 1766 | issue = 1 | pages = 63–78 | year = 2006 | month = August | pmid = 16675129 | doi = 10.1016/j.bbcan.2006.03.001 }}</ref> and failure of [[immune surveillance]], the removal of malignant cells throughout one's life by the [[immune system]].<ref name="immune">{{Cite web|author=Farlex |year=2005 |title=Immunological Surveilliance |url=http://medical-dictionary.thefreedictionary.com/immunological+surveillance |publisher=The Free Dictionary |accessdate=2008-02-10}}</ref> | * 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 = Biochimica et Biophysica Acta | volume = 1766 | issue = 1 | pages = 63–78 | year = 2006 | month = August | pmid = 16675129 | doi = 10.1016/j.bbcan.2006.03.001 }}</ref> and failure of [[immune surveillance]], the removal of malignant cells throughout one's life by the [[immune system]].<ref name="immune">{{Cite web|author=Farlex |year=2005 |title=Immunological Surveilliance |url=http://medical-dictionary.thefreedictionary.com/immunological+surveillance |publisher=The Free Dictionary |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.<ref name="pmid12817994">{{cite journal | author = Haslam SZ, Woodward TL | title = Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland. | journal = Breast Cancer Res. | volume = 5 | issue = 4 | pages = 208–15 | year = 2003 | month = June | pmid = 12817994 | pmc = 165024 | doi = 10.1186/bcr615 }}</ref><ref>{{cite journal | author = Wiseman BS, Werb Z | title = Stromal effects on mammary gland development and breast cancer | journal = Science | volume = 296 | issue = 5570 | pages = 1046–9 | year = 2002 | month = May | pmid = 12004111 | pmc = 2788989 | doi = 10.1126/science.1067431 }}</ref> In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.<ref name="pmid20889333">{{cite journal | author = Jardé T, Perrier S, Vasson MP, Caldefie-Chézet F | title = Molecular mechanisms of leptin and adiponectin in breast cancer | journal = Eur. J. Cancer | volume = 47 | issue = 1 | pages = 33–43 | year = 2011 | month = January | pmid = 20889333 | doi = 10.1016/j.ejca.2010.09.005 }}</ref> | Abnormal [[growth factor]] signaling in the interaction between [[stromal cell]]s and [[epithelial cell]]s can facilitate malignant cell growth.<ref name="pmid12817994">{{cite journal | author = Haslam SZ, Woodward TL | title = Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland. | journal = Breast Cancer Res. | volume = 5 | issue = 4 | pages = 208–15 | year = 2003 | month = June | pmid = 12817994 | pmc = 165024 | doi = 10.1186/bcr615 }}</ref><ref>{{cite journal | author = Wiseman BS, Werb Z | title = Stromal effects on mammary gland development and breast cancer | journal = Science | volume = 296 | issue = 5570 | pages = 1046–9 | year = 2002 | month = May | pmid = 12004111 | pmc = 2788989 | doi = 10.1126/science.1067431 }}</ref> In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.<ref name="pmid20889333">{{cite journal | author = Jardé T, Perrier S, Vasson MP, Caldefie-Chézet F | title = Molecular mechanisms of leptin and adiponectin in breast cancer | journal = Eur. J. Cancer | volume = 47 | issue = 1 | pages = 33–43 | year = 2011 | month = January | pmid = 20889333 | doi = 10.1016/j.ejca.2010.09.005 }}</ref> | ||
* In the United States, 10 to 20 percent of patients with breast cancer or ovarian cancer have a first- or second-degree relative with one of these diseases. The familial tendency to develop these cancers is called [[hereditary breast—ovarian cancer syndrome]]. The best known of these, the [[BRCA mutation]]s, confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as ''[[p53]]'', ''[[BRCA1]]'' and ''[[BRCA2]]'', occur in mechanisms to correct errors in DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which lead to uncontrolled division, lack of attachment, and metastasis to distant organs.<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|format=PDF |archiveurl = http://web.archive.org/web/20070613192148/http://www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf |archivedate = June 13, 2007}}</ref><ref>{{cite journal | author = Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF | title = A systematic review of genetic polymorphisms and breast cancer risk | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 8 | issue = 10 | pages = 843–54 | year = 1999 | month = October | pmid = 10548311 | doi = | url = http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10548311 }}</ref>However, there is strong evidence of residual risk variation that goes well beyond hereditary BRCA gene mutations between carrier families; this is caused by unobserved risk factors.<ref>{{cite journal | author = Begg CB, Haile RW, Borg A, ''et al.'' | title = Variation of breast cancer risk among BRCA1/2 carriers | journal = JAMA | volume = 299 | issue = 2 | pages = 194–201 | year = 2008 | month = January | pmid = 18182601 | pmc = 2714486 | doi = 10.1001/jama.2007.55-a }}</ref> It implicates that environmental factors and other causes are triggers for breast cancer. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein).<ref>{{cite journal | author = Patel KJ, Yu VP, Lee H, ''et al.'' | title = Involvement of Brca2 in DNA repair | journal = Mol. Cell | volume = 1 | issue = 3 | pages = 347–57 | year = 1998 | month = February | pmid = 9660919 | doi = 10.1016/S1097-2765(00)80035-0 }}</ref> Because of this repair deficit, risks from carcinogenic chemicals and ionizing radiation can increase.<ref name="Friedenson00">{{cite journal | author = Friedenson B | title = Is mammography indicated for women with defective BRCA genes? Implications of recent scientific advances for the diagnosis, treatment, and prevention of hereditary breast cancer | journal = MedGenMed | volume = 2 | issue = 1 | pages = E9 | year = 2000 | month = March | pmid = 11104455 | doi = | url = http://www.medscape.com/Medscape/GeneralMedicine/journal/2000/v02.n02/mgm0309.frie/mgm0309.frie-01.html }}</ref>These carcinogens cause DNA damage, such as to DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2.<ref>{{cite journal | author = Marietta C, Thompson LH, Lamerdin JE, Brooks PJ | title = Acetaldehyde stimulates FANCD2 monoubiquitination, H2AX phosphorylation, and BRCA1 phosphorylation in human cells in vitro: implications for alcohol-related carcinogenesis | journal = Mutat. Res. | volume = 664 | issue = 1-2 | pages = 77–83 | year = 2009 | month = May | pmid = 19428384 | pmc = 2807731 | doi = 10.1016/j.mrfmmm.2009.03.011 }}</ref><ref>{{cite journal | author = Theruvathu JA, Jaruga P, Nath RG, Dizdaroglu M, Brooks PJ | title = Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde | journal = Nucleic Acids Res. | volume = 33 | issue = 11 | pages = 3513–20 | year = 2005 | pmid = 15972793 | pmc = 1156964 | doi = 10.1093/nar/gki661 }}</ref> But it is these repair pathways that can be crippled by inherited mutation. There is evidence that cancer risks increase in mutation carriers exposed to such opportunistic carcinogens.<ref>{{cite journal | author = Friedenson B | title = Preventing hereditary cancers caused by opportunistic carcinogens | journal = J Med Med Sci | volume = 3 | issue = | pages = 160–178 | year = 2012 | pmid = | doi = | url = http://interesjournals.org/JMMS/Contents/2012%20Contents/March.htm }}</ref> Thus, risks for cancers may be reduced by avoiding or compensating for carcinogens that exploit the inherited BRCA gene deficiency<ref>Friedenson B, [http://www.scivee.tv/node/39255 “Preventing hereditary cancers associated with BRCA1 and BRCA2 gene mutations”] 2012</ref> However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers.<ref>{{cite journal | author = Wooster R, Weber BL | title = Breast and ovarian cancer | journal = N. Engl. J. Med. | volume = 348 | issue = 23 | pages = 2339–47 | year = 2003 | month = June | pmid = 12788999 | doi = 10.1056/NEJMra012284 }}</ref> About half of hereditary breast–ovarian cancer syndromes involve unknown genes. | |||
In the United States, 10 to 20 percent of patients with breast cancer or ovarian cancer have a first- or second-degree relative with one of these diseases. The familial tendency to develop these cancers is called [[hereditary breast—ovarian cancer syndrome]]. The best known of these, the [[BRCA mutation]]s, confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as ''[[p53]]'', ''[[BRCA1]]'' and ''[[BRCA2]]'', occur in mechanisms to correct errors in DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which lead to uncontrolled division, lack of attachment, and metastasis to distant organs.<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|format=PDF |archiveurl = http://web.archive.org/web/20070613192148/http://www.cancer.org/downloads/STT/CAFF2005BrFacspdf2005.pdf |archivedate = June 13, 2007}}</ref><ref>{{cite journal | author = Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF | title = A systematic review of genetic polymorphisms and breast cancer risk | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 8 | issue = 10 | pages = 843–54 | year = 1999 | month = October | pmid = 10548311 | doi = | url = http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10548311 }}</ref>However, there is strong evidence of residual risk variation that goes well beyond hereditary BRCA gene mutations between carrier families; this is caused by unobserved risk factors.<ref>{{cite journal | author = Begg CB, Haile RW, Borg A, ''et al.'' | title = Variation of breast cancer risk among BRCA1/2 carriers | journal = JAMA | volume = 299 | issue = 2 | pages = 194–201 | year = 2008 | month = January | pmid = 18182601 | pmc = 2714486 | doi = 10.1001/jama.2007.55-a }}</ref> It implicates that environmental factors and other causes are triggers for breast cancer. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein).<ref>{{cite journal | author = Patel KJ, Yu VP, Lee H, ''et al.'' | title = Involvement of Brca2 in DNA repair | journal = Mol. Cell | volume = 1 | issue = 3 | pages = 347–57 | year = 1998 | month = February | pmid = 9660919 | doi = 10.1016/S1097-2765(00)80035-0 }}</ref> Because of this repair deficit, risks from carcinogenic chemicals and ionizing radiation can increase.<ref name="Friedenson00">{{cite journal | author = Friedenson B | title = Is mammography indicated for women with defective BRCA genes? Implications of recent scientific advances for the diagnosis, treatment, and prevention of hereditary breast cancer | journal = MedGenMed | volume = 2 | issue = 1 | pages = E9 | year = 2000 | month = March | pmid = 11104455 | doi = | url = http://www.medscape.com/Medscape/GeneralMedicine/journal/2000/v02.n02/mgm0309.frie/mgm0309.frie-01.html }}</ref>These carcinogens cause DNA damage, such as to DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2.<ref>{{cite journal | author = Marietta C, Thompson LH, Lamerdin JE, Brooks PJ | title = Acetaldehyde stimulates FANCD2 monoubiquitination, H2AX phosphorylation, and BRCA1 phosphorylation in human cells in vitro: implications for alcohol-related carcinogenesis | journal = Mutat. Res. | volume = 664 | issue = 1-2 | pages = 77–83 | year = 2009 | month = May | pmid = 19428384 | pmc = 2807731 | doi = 10.1016/j.mrfmmm.2009.03.011 }}</ref><ref>{{cite journal | author = Theruvathu JA, Jaruga P, Nath RG, Dizdaroglu M, Brooks PJ | title = Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde | journal = Nucleic Acids Res. | volume = 33 | issue = 11 | pages = 3513–20 | year = 2005 | pmid = 15972793 | pmc = 1156964 | doi = 10.1093/nar/gki661 }}</ref> But it is these repair pathways that can be crippled by inherited mutation. There is evidence that cancer risks increase in mutation carriers exposed to such opportunistic carcinogens.<ref>{{cite journal | author = Friedenson B | title = Preventing hereditary cancers caused by opportunistic carcinogens | journal = J Med Med Sci | volume = 3 | issue = | pages = 160–178 | year = 2012 | pmid = | doi = | url = http://interesjournals.org/JMMS/Contents/2012%20Contents/March.htm }}</ref> Thus, risks for cancers may be reduced by avoiding or compensating for carcinogens that exploit the inherited BRCA gene deficiency<ref>Friedenson B, [http://www.scivee.tv/node/39255 “Preventing hereditary cancers associated with BRCA1 and BRCA2 gene mutations”] 2012</ref> However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers.<ref>{{cite journal | author = Wooster R, Weber BL | title = Breast and ovarian cancer | journal = N. Engl. J. Med. | volume = 348 | issue = 23 | pages = 2339–47 | year = 2003 | month = June | pmid = 12788999 | doi = 10.1056/NEJMra012284 }}</ref> About half of hereditary breast–ovarian cancer syndromes involve unknown genes. | |||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
Shown below is a micrograph of high grade invasive ductal carcinoma showing minimal tubule formation,marked pleomorphism, and numerous mitotic figures.<br> | Shown below is a micrograph of high grade invasive ductal carcinoma showing minimal tubule formation,marked pleomorphism, and numerous mitotic figures.<br> | ||
Revision as of 20:24, 4 March 2016
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Genes involved in the pathogenesis of breast cancer include BRCA1, BRCA2 and p53.
Genetics
- 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:
- 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.
- 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, it is necessary to promote new blood vessel growth near new cancers.
- Inherited defects in DNA repair genes, such as BRCA1, BRCA2 and p53.
- Breast cancer, like other cancers, occurs because of an interaction between the environment and a defective gene. Normal cells divide as many times as needed and stop; they attach to other cells and stay in place in tissues. Cells become cancerous when mutations destroy their ability to stop dividing, to attach to other cells, and to stay where they belong.
- Normal cells will commit cell suicide (apoptosis) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways. One of the protective pathways is the PI3K/AKT pathway; another one is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTEN protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide. In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.[2]
- Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure[1] and failure of immune surveillance, the removal of malignant cells throughout one's life by the immune system.[3]
Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.[4][5] In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.[6]
- In the United States, 10 to 20 percent of patients with breast cancer or ovarian cancer have a first- or second-degree relative with one of these diseases. The familial tendency to develop these cancers is called hereditary breast—ovarian cancer syndrome. The best known of these, the BRCA mutations, confer a lifetime risk of breast cancer of between 60 and 85 percent and a lifetime risk of ovarian cancer of between 15 and 40 percent. Some mutations associated with cancer, such as p53, BRCA1 and BRCA2, occur in mechanisms to correct errors in DNA. These mutations are either inherited or acquired after birth. Presumably, they allow further mutations, which lead to uncontrolled division, lack of attachment, and metastasis to distant organs.[7][8]However, there is strong evidence of residual risk variation that goes well beyond hereditary BRCA gene mutations between carrier families; this is caused by unobserved risk factors.[9] It implicates that environmental factors and other causes are triggers for breast cancer. The inherited mutation in BRCA1 or BRCA2 genes can interfere with repair of DNA cross links and DNA double strand breaks (known functions of the encoded protein).[10] Because of this repair deficit, risks from carcinogenic chemicals and ionizing radiation can increase.[11]These carcinogens cause DNA damage, such as to DNA cross links and double strand breaks that often require repairs by pathways containing BRCA1 and BRCA2.[12][13] But it is these repair pathways that can be crippled by inherited mutation. There is evidence that cancer risks increase in mutation carriers exposed to such opportunistic carcinogens.[14] Thus, risks for cancers may be reduced by avoiding or compensating for carcinogens that exploit the inherited BRCA gene deficiency[15] However, mutations in BRCA genes account for only 2 to 3 percent of all breast cancers.[16] About half of hereditary breast–ovarian cancer syndromes involve unknown genes.
Microscopic Pathology
Shown below is a micrograph of high grade invasive ductal carcinoma showing minimal tubule formation,marked pleomorphism, and numerous mitotic figures.
References
- ↑ 1.0 1.1 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.
- ↑ "32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium" (PDF). Sunday Morning Year-End Review. Dec. 14, 2009. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ Farlex (2005). "Immunological Surveilliance". The Free Dictionary. Retrieved 2008-02-10.
- ↑ Haslam SZ, Woodward TL (2003). "Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland". Breast Cancer Res. 5 (4): 208–15. doi:10.1186/bcr615. PMC 165024. PMID 12817994. Unknown parameter
|month=ignored (help) - ↑ Wiseman BS, Werb Z (2002). "Stromal effects on mammary gland development and breast cancer". Science. 296 (5570): 1046–9. doi:10.1126/science.1067431. PMC 2788989. PMID 12004111. Unknown parameter
|month=ignored (help) - ↑ Jardé T, Perrier S, Vasson MP, Caldefie-Chézet F (2011). "Molecular mechanisms of leptin and adiponectin in breast cancer". Eur. J. Cancer. 47 (1): 33–43. doi:10.1016/j.ejca.2010.09.005. PMID 20889333. Unknown parameter
|month=ignored (help) - ↑ American Cancer Society (2005). "Breast Cancer Facts & Figures 2005–2006" (PDF). Archived from the original (PDF) on June 13, 2007. Retrieved 2007-04-26.
- ↑ Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF (1999). "A systematic review of genetic polymorphisms and breast cancer risk". Cancer Epidemiology, Biomarkers & Prevention. 8 (10): 843–54. PMID 10548311. Unknown parameter
|month=ignored (help) - ↑ Begg CB, Haile RW, Borg A; et al. (2008). "Variation of breast cancer risk among BRCA1/2 carriers". JAMA. 299 (2): 194–201. doi:10.1001/jama.2007.55-a. PMC 2714486. PMID 18182601. Unknown parameter
|month=ignored (help) - ↑ Patel KJ, Yu VP, Lee H; et al. (1998). "Involvement of Brca2 in DNA repair". Mol. Cell. 1 (3): 347–57. doi:10.1016/S1097-2765(00)80035-0. PMID 9660919. Unknown parameter
|month=ignored (help) - ↑ Friedenson B (2000). "Is mammography indicated for women with defective BRCA genes? Implications of recent scientific advances for the diagnosis, treatment, and prevention of hereditary breast cancer". MedGenMed. 2 (1): E9. PMID 11104455. Unknown parameter
|month=ignored (help) - ↑ Marietta C, Thompson LH, Lamerdin JE, Brooks PJ (2009). "Acetaldehyde stimulates FANCD2 monoubiquitination, H2AX phosphorylation, and BRCA1 phosphorylation in human cells in vitro: implications for alcohol-related carcinogenesis". Mutat. Res. 664 (1–2): 77–83. doi:10.1016/j.mrfmmm.2009.03.011. PMC 2807731. PMID 19428384. Unknown parameter
|month=ignored (help) - ↑ Theruvathu JA, Jaruga P, Nath RG, Dizdaroglu M, Brooks PJ (2005). "Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde". Nucleic Acids Res. 33 (11): 3513–20. doi:10.1093/nar/gki661. PMC 1156964. PMID 15972793.
- ↑ Friedenson B (2012). "Preventing hereditary cancers caused by opportunistic carcinogens". J Med Med Sci. 3: 160–178.
- ↑ Friedenson B, “Preventing hereditary cancers associated with BRCA1 and BRCA2 gene mutations” 2012
- ↑ Wooster R, Weber BL (2003). "Breast and ovarian cancer". N. Engl. J. Med. 348 (23): 2339–47. doi:10.1056/NEJMra012284. PMID 12788999. Unknown parameter
|month=ignored (help)