Difference between revisions of "Invasive breast cancer"

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Invasive breast cancer (view source)

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→‎Invasive versus non-invasive: added information from recent study on microinvasion
(→‎Invasive versus non-invasive: added information from recent study on microinvasion)
 
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Papillary:
Papillary:
*[[Intraductal papilloma|Papilloma]].
*[[Intraductal papilloma of the breast|Papilloma]].
*Atypical papilloma.
*Atypical papilloma.
*Intraductal papillary carcinoma.
*Intraductal papillary carcinoma.
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The above is not applied clinically. A panel of [[immunostains]] (ER, PR, HER2, EGFR, CK5/6) can reproduce the molecular groupings; however, these groupings originate from gene expression profiling studies<ref name=pmid19704256>{{Cite journal  | last1 = Tang | first1 = P. | last2 = Skinner | first2 = KA. | last3 = Hicks | first3 = DG. | title = Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? | journal = Diagn Mol Pathol | volume = 18 | issue = 3 | pages = 125-32 | month = Sep | year = 2009 | doi = 10.1097/PDM.0b013e31818d107b | PMID = 19704256 }}</ref>
The above is not applied clinically. A panel of [[immunostains]] ([[ER]], PR, HER2, EGFR, [[CK5/6]]) can reproduce the molecular groupings; however, these groupings originate from gene expression profiling studies<ref name=pmid19704256>{{Cite journal  | last1 = Tang | first1 = P. | last2 = Skinner | first2 = KA. | last3 = Hicks | first3 = DG. | title = Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? | journal = Diagn Mol Pathol | volume = 18 | issue = 3 | pages = 125-32 | month = Sep | year = 2009 | doi = 10.1097/PDM.0b013e31818d107b | PMID = 19704256 }}</ref>


A newer classification outlines 10 subtypes based on molecular drivers identified by analysis of genomic and transcriptomic data from 2,000 breast tumors.<ref>{{Cite journal  | last1 = Curtis | first1 = C. | last2 = Shah | first2 = SP. | last3 = Chin | first3 = SF. | last4 = Turashvili | first4 = G. | last5 = Rueda | first5 = OM. | last6 = Dunning | first6 = MJ. | last7 = Speed | first7 = D. | last8 = Lynch | first8 = AG. | last9 = Samarajiwa | first9 = S. | title = The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. | journal = Nature | volume = 486 | issue = 7403 | pages = 346-52 | month = Jun | year = 2012 | doi = 10.1038/nature10983 | PMID = 22522925 }}</ref>
A newer classification outlines 10 subtypes based on molecular drivers identified by analysis of genomic and transcriptomic data from 2,000 breast tumors.<ref>{{Cite journal  | last1 = Curtis | first1 = C. | last2 = Shah | first2 = SP. | last3 = Chin | first3 = SF. | last4 = Turashvili | first4 = G. | last5 = Rueda | first5 = OM. | last6 = Dunning | first6 = MJ. | last7 = Speed | first7 = D. | last8 = Lynch | first8 = AG. | last9 = Samarajiwa | first9 = S. | title = The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. | journal = Nature | volume = 486 | issue = 7403 | pages = 346-52 | month = Jun | year = 2012 | doi = 10.1038/nature10983 | PMID = 22522925 }}</ref>


== Basal-like breast carcinoma==
== Basal-like breast carcinoma==
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| stains myofibroblasts & blood vessels
| stains myofibroblasts & blood vessels
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Respecting findings that might indicate a more extensive search for microinvasion be undertaken in cases of pure ductal carcinoma in situ (DCIS), a recent study found 1) intermediate or high DCIS grade, 2) tumor thickness, and 3) diffuse peritumoral retraction clefts, but not such things as lymph node metastases, or HER2 score, independently increased the likelihood of finding a microinvasive component. <ref name=pmid28434924>{{cite journal |author=Mori K, Takeda M, Kodama Y, Kiyokawa H, Yasojima H, Mizutani M, Otani Y, Morikawa N, Masuda N, Mano M|title= Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ |journal=Human Pathology |volume=64 |issue= |pages=145-155 |year=2017 | pmid=28434924 |doi=10.1016/j.humpath.2017.04.004 }}</ref>


===Usual ductal hyperplasia versus ductal carcinoma in situ===
===Usual ductal hyperplasia versus ductal carcinoma in situ===
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{| class="wikitable sortable"  
{| class="wikitable sortable"  
!Disease  
!Disease  
!CK5/6
![[CK5/6]]
!ER
![[ER]]
|-
|-
|UDH
|UDH
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*CD31 - marks lymphovascular spaces.
*CD31 - marks lymphovascular spaces.
*CD34 - marks lymphovascular spaces, less specific than CD31.
*CD34 - marks lymphovascular spaces, less specific than CD31.
===Lymph node metastases===
Immunostaining of sentinel lymph nodes to look for [[isolated tumour cells]] and small [[lymph node metastases]] may be done.
*CAM5.2 may be used.
*'''Not''' done routinely.


==Treatment-related markers - overview==
==Treatment-related markers - overview==
*Immunostaining of sentinel lymph nodes to look for isolated tumour cells and small lymph node mets.
**CAM5.2 may be used.
**Not done routinely.
*ER (estrogen receptor).
*ER (estrogen receptor).
**Positive in most breast cancers; +ve in ~75-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
**Positive in most breast cancers; +ve in ~75-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
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**In the context of HER2 positivity, PTEN/PI3K/Akt/mTOR pathway dysregulation is a poor prognosticator.<ref name=pmid22454081>{{Cite journal  | last1 = Gallardo | first1 = A. | last2 = Lerma | first2 = E. | last3 = Escuin | first3 = D. | last4 = Tibau | first4 = A. | last5 = Muñoz | first5 = J. | last6 = Ojeda | first6 = B. | last7 = Barnadas | first7 = A. | last8 = Adrover | first8 = E. | last9 = Sánchez-Tejada | first9 = L. | title = Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. | journal = Br J Cancer | volume = 106 | issue = 8 | pages = 1367-73 | month = Apr | year = 2012 | doi = 10.1038/bjc.2012.85 | PMID = 22454081 }}</ref><ref name=pmid22172323>{{Cite journal  | last1 = Jensen | first1 = JD. | last2 = Knoop | first2 = A. | last3 = Laenkholm | first3 = AV. | last4 = Grauslund | first4 = M. | last5 = Jensen | first5 = MB. | last6 = Santoni-Rugiu | first6 = E. | last7 = Andersson | first7 = M. | last8 = Ewertz | first8 = M. | title = PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. | journal = Ann Oncol | volume =  | issue =  | pages =  | month = Dec | year = 2011 | doi = 10.1093/annonc/mdr546 | PMID = 22172323 }}</ref>  
**In the context of HER2 positivity, PTEN/PI3K/Akt/mTOR pathway dysregulation is a poor prognosticator.<ref name=pmid22454081>{{Cite journal  | last1 = Gallardo | first1 = A. | last2 = Lerma | first2 = E. | last3 = Escuin | first3 = D. | last4 = Tibau | first4 = A. | last5 = Muñoz | first5 = J. | last6 = Ojeda | first6 = B. | last7 = Barnadas | first7 = A. | last8 = Adrover | first8 = E. | last9 = Sánchez-Tejada | first9 = L. | title = Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. | journal = Br J Cancer | volume = 106 | issue = 8 | pages = 1367-73 | month = Apr | year = 2012 | doi = 10.1038/bjc.2012.85 | PMID = 22454081 }}</ref><ref name=pmid22172323>{{Cite journal  | last1 = Jensen | first1 = JD. | last2 = Knoop | first2 = A. | last3 = Laenkholm | first3 = AV. | last4 = Grauslund | first4 = M. | last5 = Jensen | first5 = MB. | last6 = Santoni-Rugiu | first6 = E. | last7 = Andersson | first7 = M. | last8 = Ewertz | first8 = M. | title = PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. | journal = Ann Oncol | volume =  | issue =  | pages =  | month = Dec | year = 2011 | doi = 10.1093/annonc/mdr546 | PMID = 22172323 }}</ref>  


Note:
Notes:
*Male breast cancer is usually hormone receptor positive (~97%), and HER2 positivity is quite rare (~6%).<ref name=pmid24080492>{{Cite journal  | last1 = Schildhaus | first1 = HU. | last2 = Schroeder | first2 = L. | last3 = Merkelbach-Bruse | first3 = S. | last4 = Binot | first4 = E. | last5 = Büttner | first5 = R. | last6 = Kuhn | first6 = W. | last7 = Rudlowski | first7 = C. | title = Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes. | journal = Breast | volume =  | issue =  | pages =  | month = Sep | year = 2013 | doi = 10.1016/j.breast.2013.08.008 | PMID = 24080492 }}</ref>  
*Male breast cancer is usually hormone receptor positive (~97%), and HER2 positivity is quite rare (~6%).<ref name=pmid24080492>{{Cite journal  | last1 = Schildhaus | first1 = HU. | last2 = Schroeder | first2 = L. | last3 = Merkelbach-Bruse | first3 = S. | last4 = Binot | first4 = E. | last5 = Büttner | first5 = R. | last6 = Kuhn | first6 = W. | last7 = Rudlowski | first7 = C. | title = Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes. | journal = Breast | volume =  | issue =  | pages =  | month = Sep | year = 2013 | doi = 10.1016/j.breast.2013.08.008 | PMID = 24080492 }}</ref>  
*ASCO/CAP guidelines recommend that cold ischemia time be <1 hour.<ref name=pmid22460807 >{{Cite journal  | last1 = Yildiz-Aktas | first1 = IZ. | last2 = Dabbs | first2 = DJ. | last3 = Bhargava | first3 = R. | title = The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma. | journal = Mod Pathol | volume = 25 | issue = 8 | pages = 1098-105 | month = Aug | year = 2012 | doi = 10.1038/modpathol.2012.59 | PMID = 22460807 }}</ref>
===ER & PR scoring===
===ER & PR scoring===
Nuclear staining:<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
Nuclear staining:<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
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=Grading breast cancer=
=Grading breast cancer=
Most common system: ''Nottingham'' (aka Scarff-Bloom-Richardson) which is based on:
{{Main|Breast cancer grading}}
#Nuclear grade.
#*Small, regular (1.5-2x RBC dia.) = 1.
#*Moderated variability = 2.
#*Marked variation (>2.5x RBC dia.) = 3.
# Tubule formation.
#*Majority of tumour - tubules >75% = 1.
#*Moderate - 10% to 75% = 2.
#*Minimal <10% = 3.
# Mitotic rate.
#*0-5 mitosis/10 [[HPF]] (1.52 mm^2 --or-- 0.0152 mm^2 * 10) = 1.
#*6-10 mitosis/10 HPF (1.52 mm^2) = 2.
#*>11 mitosis/10 HPF (1.52 mm^2) = 3.
Mnemonic: ''TMN'' = tubule formation, mitotic rate, nuclear grade.
 
Notes:
*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==
*One MUST adjust for the size of the field of view.
 
*Most of the Resident scopes have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.
**Thus, on a resident scope (with a FOV of 0.2376 mm^2) one should sample 6 or 7 fields of view (FsOV).
***Calculation: 1.52 mm^2 (sampling area) / 0.2376 mm^2 (area / FOV ) = 6.40 FsOV.
 
*'''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==
*Grade I = 3-5 points.
*Grade II = 6-7 points.
*Grade III = 8-9 points.
 
Notes:
*I've found most tumours are grade II. 
*The mitotic score is usually 1/3.
*The nuclear score is rarely 1/3 -- even in the tubular subtype.<ref>MUA. 20 January 2009.</ref>


=Staging breast cancer=
=Staging breast cancer=
==Sentinel lymph node sampling in breast cancer==
{{Main|Breast cancer staging}}
{{Main|Sentinel lymph node|Lymph node metastasis}}
===General===
*Selective sampling of lymph nodes.
*Used for staging.
*Positive LNs = poorer prognosis.
 
Notes:
*If there is no palpable disease, there is '''no''' mortality benefit from axillary lymph node dissection, i.e. positive axillary lymph nodes can be left in situ without affecting outcome.<ref>{{cite journal |author=Giuliano AE, Hunt KK, Ballman KV, ''et al.'' |title=Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial |journal=JAMA |volume=305 |issue=6 |pages=569–75 |year=2011 |month=February |pmid=21304082 |doi=10.1001/jama.2011.90 |url=}}</ref>
**This does not negate the fact that a positive sentinel LN biopsy (vs. negative sentinel LN biopsy) portends a poorer prognosis.
 
===Microscopic===
Features:
*Atypical cells.
**Nuclear changes of malignancy:
***Nuclear enlargement + variation in size.
***Variation in shape.
***Hyperchromasia and variation in staining.
**Usually in the subcapsular sinuses.
 
Pitfalls:
*Naevus cell rests.<ref>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html]. Accessed on: 28 November 2010.</ref>
 
===IHC===
Some hospitals use:
*CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.
 
==N stage==
Sampling usually selective, i.e. [[sentinel lymph nodes]] only.
===Indications for lymph node sampling===<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf]. Accessed on: 2 April 2012.</ref>
*Extensive [[DCIS]].
*Biopsy suspicious for invasion ''or'' with microinvasion.
*Clinical findings (large palable mass) or radiology findings (irregular features) suggestive of invasion.
*Planned mastectomy.
 
===Definitions===
Definitions:<ref name=acs_website>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 ''or'' <=200 cells -- in a single cross-section. †
*Micrometastasis: <=0.2 cm ''and'' ( >0.2 mm ''or'' >200 cells ).
*Macrometastasis: >0.2 cm.
 
Notes:
* † The ''American Cancer Society'' web site says "or".<ref name=acs_website/>  The CAP protocol says "and/or" and notes it is all subjective.
*Isolated tumour cells are essentially ignored if the there is at least one macrometastasis.
 
===Details===
Lymph nodes:<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>
*pN0: nil.
**pN0(i+): <=0.2 mm ''and'' <200 cells.
*pN1: 1-3 axillary LNs ''or'' internal mammary LNs.
**pN1mi: <=0.2 cm ''and'' ( >0.2 mm ''or'' >=200 cells ).
**pN1a.
**pN1b.
**PN1c.
*pN2 4-9 positive LNs; internal mammary LNs ''or'' axillary LNs.
*pN3.
 
==T stage==
Tumour:<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><ref>URL: [http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging]. Accessed on: 9 July 2010.</ref>
*pT1: <= 20 mm.
**pT1mic <= 1 mm.
**pT1a > 1 mm ''and'' <= 5 mm.
**pT1b > 5 mm ''and'' <= 10 mm.
**pT1c > 10 mm ''and'' <= 20 mm.
*pT2: > 20 mm and <= 50 mm
*pT3: > 50 mm.
*pT4: chest wall or skin involvement.
 
Notes:
*Values should be rounded to the nearest millimetre.
**Therefore:
***1.4 mm would be ''pT1mic''.
***1.5 mm would be ''pT1a''.
 
==M stage==
Distant metastasis:
*cM0(i+) <=0.2 mm focus of tumour cells, without clinical signs and symptoms.
*pM1 focus of tumour cells > 0.2 mm.


=Lymphovascular invasion=
=Lymphovascular invasion=
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=External links=
=External links=
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees%2Fcancer%2Fcancer_protocols%2Fprotocols_index.html&_state=maximized&_pageLabel=cntvwr CAP protocols/checklists (cap.org)].
**[http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf Invasive breast cancer - checklist (cap.org)].
*[http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html About breast cancer - molecular subtypes (komen.org)].
*[http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html About breast cancer - molecular subtypes (komen.org)].


[[Category:Breast pathology]]
[[Category:Breast pathology]]
[[Category:Invasive breast cancer]]
[[Category:Invasive breast cancer]]
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