Difference between revisions of "Invasive breast cancer"

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The article deals with '''invasive [[breast]] cancer''' and the evaluation of hormone receptor & HER2 status.  Non-invasive breast cancer is dealt with in ''[[non-invasive breast cancer]]''.
The article deals with '''invasive [[breast]] cancer''' and the evaluation of hormone receptor & HER2 status.  Non-invasive breast cancer is dealt with in ''[[non-invasive breast cancer]]''.


=Introduction=
==Types of invasive breast cancer==
==Types of invasive breast cancer==
Types:Ref.: <ref name=Ref_PBoD1143>{{Ref PBoD|1143}}</ref>
Types:Ref.: <ref name=Ref_PBoD1143>{{Ref PBoD|1143}}</ref>
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*[[Angiosarcoma]] - post-radiation ~ 10 years.<ref>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html]. Accessed on: 28 November 2010.</ref>
*[[Angiosarcoma]] - post-radiation ~ 10 years.<ref>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html]. Accessed on: 28 November 2010.</ref>


==Standard IHC work-up==
==Familial breast cancer==
===Overview===
BRCA1 vs. BRCA2:<ref name=Ref_PBoD1133>{{Ref PBoD|1133}}</ref>
*BRCA1:
**Younger.
**Ovarian cancer.
**Worse types of breast cancer (e.g. triple negative breast cancer: PR-, ER-, HER2/neu-).
*BRCA2:
**Older.
**Like sporatic.
**Male [[breast cancer]].
*BOTH associated with increased risk of:
**[[Prostate]].
**[[Pancreas]].
**[[Colon cancer]].
 
=Breast IHC=
==Subtyping breast cancer==
 
*DCIS vs LCIS:<ref>{{cite journal |author=Yeh IT, Mies C |title=Application of immunohistochemistry to breast lesions |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=349-58 |year=2008 |month=March |pmid=18318578 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349}}</ref>
**E-cadherin (+ve DCIS, -ve LCIS).
**antibody 34betaE12 (+ve perinuclear LCIS, -ve DCIS).
**CAM5.2 (peripheral stain = DCIS, perinuclear stain = LCIS).
***CAM5.2 is against CK8.
**Beta-catenin (-LCIS, +DCIS).
 
*D2-40:<ref>{{cite journal |author=Ordóñez NG |title=Podoplanin: a novel diagnostic immunohistochemical marker |journal=Adv Anat Pathol |volume=13 |issue=2 |pages=83-8 |year=2006 |month=March |pmid=16670463 |doi=10.1097/01.pap.0000213007.48479.94 |url=}}</ref><ref>{{cite journal |author=Kahn HJ, Marks A |title=A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors |journal=Lab. Invest. |volume=82 |issue=9 |pages=1255-7 |year=2002 |month=September |pmid=12218087 |doi= |url=}}</ref>
**Monoclonal antibody to podoplanin.
**Useful to assess lymphovascular invasion.
 
*ADH and DCIS:<ref name=Ref_Lester122>{{Ref Lester|122}}</ref>
**E-cadherin.
***Present in most epithelial cells.
***Lost in LCIS & invasive lobular carcinoma.
**SMMHC (smooth muscle cell myosin heavy chain).
***Marks myoepithelial cells.
 
==Treatment-related markers - overview==
*Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
*Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
**Sunnybrook uses ''CAM5.2''.
**Sunnybrook uses ''CAM5.2''.
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*HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.
*HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.


==Characteristics of the subtypes==
=Characteristics of the subtypes=
===Ductal===
==Ductal==
AKA "NST" = No Specific Type.
*[[AKA]] "NST" = No Specific Type.


Micro.
===Microscopic===
Features:
*Cohesive cells - forming ducts or in sheets.
*Cohesive cells - forming ducts or in sheets.
*Nuclear pleomorphism.
*Nuclear pleomorphism.
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*Typically: ER+, PR+, HER2-.
*Typically: ER+, PR+, HER2-.


===Lobular===
==Lobular==
===General===
*May be associated with a CDH-1 mutation.<ref>URL: [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33006 http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33006]. Accessed on: 19 April 2011.</ref>
 
===Microscopic===
Features:
*"Single file" - cell line-up in a row.
*"Single file" - cell line-up in a row.
**Cell should not be cohesive -- lymphoma should briefly come to mind.  
**Cell should not be cohesive -- lymphoma should briefly come to mind.  
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Note: Some pathologist grade lobular carcinoma like other types and avoid the term "pleomorphic lobular carcinoma."<ref>MUA. Jan 22, 2009.</ref>
Note: Some pathologist grade lobular carcinoma like other types and avoid the term "pleomorphic lobular carcinoma."<ref>MUA. Jan 22, 2009.</ref>


===Medullary carcinoma===
==Medullary carcinoma==
===General===
*Some pathologists don't believe this exists.
*Some pathologists don't believe this exists.


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*Association with BRCA1 mutations.
*Association with BRCA1 mutations.


Histol.
===Microscopic===
Features:
#Lesion has well-circumscribed border.
#Lesion has well-circumscribed border.
#Syncytial growth pattern = clumps of cells with poorly defined cell borders.
#Syncytial growth pattern = clumps of cells with poorly defined cell borders.
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#No tubule formation.
#No tubule formation.


===Tubular===
==Tubular==
Epidemiology
===General===
Epidemiology:
*Typically excellent prognosis.
*Typically excellent prognosis.
*Hormone receptors commonly present.
*Hormone receptors commonly present.


====Microscopic====
===Microscopic===
Features:<ref name=Ref_PBoD1146>{{Ref PBoD|1146}}</ref><ref>URL: [http://www.bweems.com/nsj3mp2.jpg http://www.bweems.com/nsj3mp2.jpg].</ref><ref>URL: [http://surgpathcriteria.stanford.edu/breast/tubularcabr/ http://surgpathcriteria.stanford.edu/breast/tubularcabr/].</ref>
Features:<ref name=Ref_PBoD1146>{{Ref PBoD|1146}}</ref><ref>URL: [http://www.bweems.com/nsj3mp2.jpg http://www.bweems.com/nsj3mp2.jpg].</ref><ref>URL: [http://surgpathcriteria.stanford.edu/breast/tubularcabr/ http://surgpathcriteria.stanford.edu/breast/tubularcabr/].</ref>
*Well-formed tubules.
*Well-formed tubules.
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*[[sclerosing adenosis|Benign sclerosing lesion]].
*[[sclerosing adenosis|Benign sclerosing lesion]].


===Metaplastic carcinoma===
==Metaplastic carcinoma==
===General===
*May be difficult to diagnosis.
*May be difficult to diagnosis.
*Prognosis - poor.
*Prognosis - poor.


====Microscopic====
===Microscopic===
Features:<ref name=metaplastic>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html]. Accessed on: 28 November 2010.</ref>
Features:<ref name=metaplastic>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html]. Accessed on: 28 November 2010.</ref>
*Spindle cells ''or'' squamoid cells ''or'' other malignant mesenchymal elements.
*Spindle cells ''or'' squamoid cells ''or'' other malignant mesenchymal elements.
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Images: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html Metaplastic carcinoma (breastpathology.info)].<ref name=metaplastic>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html]. Accessed on: 28 November 2010.</ref>
Images: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html Metaplastic carcinoma (breastpathology.info)].<ref name=metaplastic>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html]. Accessed on: 28 November 2010.</ref>


==Grading breast cancer==
=Grading breast cancer=
Most common system: ''Nottingham'' (aka Scarff-Bloom-Richardson) which is based on:  
Most common system: ''Nottingham'' (aka Scarff-Bloom-Richardson) which is based on:  
#Nuclear grade.  
#Nuclear grade.  
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*Elston & Ellis devised the system that is used.<ref name=pmid12405945>{{cite journal |author=Elston CW, Ellis IO |title=Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403-410 |journal=Histopathology |volume=41 |issue=3A |pages=151–2, discussion 152–3 |year=2002 |month=September |pmid=12405945 |doi= |url=}}</ref> They also wrote a follow-up article in 2002.<ref name=pmid1757079>{{cite journal |author=Elston CW, Ellis IO |title=Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up |journal=Histopathology |volume=19 |issue=5 |pages=403–10 |year=1991 |month=November |pmid=1757079 |doi= |url=}}</ref>
*Elston & Ellis devised the system that is used.<ref name=pmid12405945>{{cite journal |author=Elston CW, Ellis IO |title=Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403-410 |journal=Histopathology |volume=41 |issue=3A |pages=151–2, discussion 152–3 |year=2002 |month=September |pmid=12405945 |doi= |url=}}</ref> They also wrote a follow-up article in 2002.<ref name=pmid1757079>{{cite journal |author=Elston CW, Ellis IO |title=Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up |journal=Histopathology |volume=19 |issue=5 |pages=403–10 |year=1991 |month=November |pmid=1757079 |doi= |url=}}</ref>


===Note about mitosis counting===
==Note about mitosis counting==
*One MUST adjust for the size of the field of view.
*One MUST adjust for the size of the field of view.


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*'''RANT''': Sampling 10 fields, where the field of view (FOV) is 0.152 mm^2, is ''not'' the same as sampling ten fields, where the FOV is 0.312 mm^2.  It surprises me that Elston & Ellis ignore the fact that "10 HPFs" on different microscopes represent different sample areas and that they do ''not'' standardize the sampling area.
*'''RANT''': Sampling 10 fields, where the field of view (FOV) is 0.152 mm^2, is ''not'' the same as sampling ten fields, where the FOV is 0.312 mm^2.  It surprises me that Elston & Ellis ignore the fact that "10 HPFs" on different microscopes represent different sample areas and that they do ''not'' standardize the sampling area.


===Calculating Nottingham score===
==Calculating Nottingham score==
*Grade I = 3-5 points.
*Grade I = 3-5 points.
*Grade II = 6-7 points.
*Grade II = 6-7 points.
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*The nuclear score is rarely 1/3 -- even in the tubular subtype.<ref>MUA. 20 January 2009.</ref>
*The nuclear score is rarely 1/3 -- even in the tubular subtype.<ref>MUA. 20 January 2009.</ref>


==Staging breast cancer==
=Staging breast cancer=
Definitions:<ref>URL: [http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging]. Accessed on: 8 July 2010.</ref>
Definitions:<ref>URL: [http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging]. Accessed on: 8 July 2010.</ref>
*Isolated tumour cells: <=0.2 mm ''and'' <200 cells.
*Isolated tumour cells: <=0.2 mm ''and'' <200 cells.
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*pN3.
*pN3.


==Breast IHC==
=Other=
*DCIS vs LCIS:<ref>{{cite journal |author=Yeh IT, Mies C |title=Application of immunohistochemistry to breast lesions |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=349-58 |year=2008 |month=March |pmid=18318578 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349}}</ref>
**E-cadherin (+ve DCIS, -ve LCIS).
**antibody 34betaE12 (+ve perinuclear LCIS, -ve DCIS).
**CAM5.2 (peripheral stain = DCIS, perinuclear stain = LCIS).
***CAM5.2 is against CK8.
**Beta-catenin (-LCIS, +DCIS).
 
*D2-40:<ref>{{cite journal |author=Ordóñez NG |title=Podoplanin: a novel diagnostic immunohistochemical marker |journal=Adv Anat Pathol |volume=13 |issue=2 |pages=83-8 |year=2006 |month=March |pmid=16670463 |doi=10.1097/01.pap.0000213007.48479.94 |url=}}</ref><ref>{{cite journal |author=Kahn HJ, Marks A |title=A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors |journal=Lab. Invest. |volume=82 |issue=9 |pages=1255-7 |year=2002 |month=September |pmid=12218087 |doi= |url=}}</ref>
**Monoclonal antibody to podoplanin.
**Useful to assess lymphovascular invasion.
 
*ADH and DCIS:<ref name=Ref_Lester122>{{Ref Lester|122}}</ref>
**E-cadherin.
***Present in most epithelial cells.
***Lost in LCIS & invasive lobular carcinoma.
**SMMHC (smooth muscle cell myosin heavy chain).
***Marks myoepithelial cells.
 
==Paget's disease==
==Paget's disease==
{{Main|Paget disease of the breast}}
{{Main|Paget disease of the breast}}
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IHC & DDx:  
IHC & DDx:  
*See ''[[Paget disease]]''.
*See ''[[Paget disease]]''.
==Familial breast cancer==
BRCA1 vs. BRCA2:<ref name=Ref_PBoD1133>{{Ref PBoD|1133}}</ref>
*BRCA1:
**Younger.
**Ovarian cancer.
**Worse types of breast cancer (e.g. triple negative breast cancer: PR-, ER-, HER2/neu-).
*BRCA2:
**Older.
**Like sporatic.
**Male [[breast cancer]].
*BOTH associated with increased risk of:
**[[Prostate]].
**[[Pancreas]].
**[[Colon cancer]].


==Sentinel lymph node biopsy==
==Sentinel lymph node biopsy==
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*CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.
*CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.


==See also==
=See also=
*[[Breast]].
*[[Breast]].
*[[Non-invasive breast cancer]].
*[[Non-invasive breast cancer]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Breast pathology]]
[[Category:Breast pathology]]
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