Revision as of 11:41, 20 March 2015

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

Overview of invasive breast cancer subtypes

Common epithelial subtypes

Type and percentage of breast carcinomas:^[1]

Ductal - AKA no special type (NST) - 79%.
Lobular - 10%.
Cribriform / tubular - 6%.
Mucinous (colloid) - 2%.
Medullary - 2%.
Papillary - 1%.
Metaplastic - <1%.

Common stromal types

Malignant phyllodes tumour.
Angiosarcoma - post-radiation ~ 10 years.^[2]

Good prognosis subtypes

Three good prognosis subtypes:^[3]

Tubular carcinoma.
Mucinous carcinoma.
Papillary carcinoma.

Comprehensive list of invasive breast cancer subtypes

Epithelial

Counterparts of in situ lesions:

Invasive ductal carinoma, not otherwise specified.
Invasive lobular carcinoma.
Invasive cribriform carcinoma.
Invasive papillary carcinoma.
Invasive micropapillary carcinoma.

Other epithelial tumours:

Epithelial tumours seen in the salivary gland:

Seen in the skin:

Sebaceous carcinoma.

Clinically diagnosed:

Inflammatory carcinoma.

In situ lesions:

Proliferative lesions:

Non-specific:

Microinvasive carcinoma.

Papillary:

Papilloma.
Atypical papilloma.
Intraductal papillary carcinoma.

Adenomas:

Ductal adenoma.
Tubular adenoma.
Lactating adenoma.
Apocrine adenoma.
Pleomorphic adenoma.

Myoepithelial

Myoepitheliosis.
Adenomyoepithelial adenosis.
Adenomyoepithelioma.
Malignant adenomyoepithelioma.

Mesenchymal tumours

See: Soft tissue lesions.

Fibroepithelial tumours

Fibroadenoma.
Phyllodes tumour.
Periductal stromal sarcoma, low grade.
Mammary hamartoma.

Nipple lesions

Nipple adenoma.
Syringomatous adenoma.
Paget disease of the breast.

Other

Lymphoma.
Metastasis.

Familial breast cancer

Main article: Hereditary breast cancer

Breast IHC

Molecular classification of invasive carcinoma

A molecular classification:^[4]

Type	Percentage	IHC	Histology	Prognosis/clinical
Luminal A	~45%	ER+ PR+ HER2-	well-differentiated	good, chemo resistant
Luminal B	17%	ER+ PR+ HER2+	high grade	poor, +/- chemo responsive
Normal breast-like	~8%	ER+ PR+ (?) HER2-	well-differentiated	good
Basal-like	~20%	ER- PR- HER2-	poorly differentiated	aggressive, may have good chemo response, classic for BRCA1 mutation
HER2 positive	~10%	ER- PR- (?) HER2+	poorly differentiated	poor

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^[5]

A newer classification outlines 10 subtypes based on molecular drivers identified by analysis of genomic and transcriptomic data from 2,000 breast tumors.^[6]

== Basal-like breast carcinoma==^[7]

Overview
- A category of breast carcinomas defined by gene expression profiling
- Somewhere between 15-30% of breast carcinomas.
- Can be identified by immunohistochemistry - basal markers (CK14, p63, calponin, SMA)
- Not derived from myoepithelial cells, merely express a phenotype more in keeping with basal cells than ductal cells
- Most triple negative (ER, PgR, Her-2); therefore cannot be treated with the usual therapeutic agents
- There is an association in young women between basal-like breast cancer and BRCA1 mutation.
- Increased incidence in some populations - African-Americans, young women
- Sporadic basal-like cancers do not have a BRCA1 mutation but may have a dysfunctional BRCA1 pathway.
- p53 mutations are frequent

This molecular group includes a variety of morphologic phenotypes including:
- High grade invasive ductal carcinoma of no special type.
- Medullary-like carcinoma (a carcinoma with some but not all the features of medullary carcinoma).
- Medullary carcinomas
- Metaplastic carcinomas
- Adenoid cystic carcinoma
- Secretory carcinoma

Classic morphological clues of a basal type cancer usually refer to medullary carcinoma features:
- Relatively circumscribed
- Geographic necrosis
- Abundant mitoses
- Pushing margins
- Central fibrosis or necrosis
- High histological grade
- Exceptionally high mitotic rate
- Pushing borders
- Conspicuous lymphocytic infiltrate

Behaviour
- Basal-like breast cancer is a heterogeneous group.
- The behaviour of basal-like breast cancer appears to fall into two groups:
  - The tumours that are by nature low grade (ie adenoid cystic carcinoma) and/or do not metastasise have a better prognosis than other types of breast carcinoma.
  - The tumours with early metastasis that may behave more aggressively
    - Hematogenous spread -greater tendency to metastasise to visceral sites (notably lung and brain) instead of to nodes and bone.
- Many have a complete response to chemotherapy and survival rates similar to typical breast cancer
- Non-complete response to chemotherapy is associated with low survival at 5 years.

Other sources Minireview: Basal-Like Breast Cancer: From Molecular Profiles to Targeted Therapies <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035993/>

== Triple Negative Breast Carcinoma ==^[8]

- A category of breast carcinomas defined by immunohistochemical/FISH expression of ER, PR and HER2.
- About 15% of breast carcinomas.
- Important group due to a lack of tailored therapies for this group
- Triple-negative and basal-like phenotypes are not synonymous but overlap
  - About 70% of triple-negative tumours are basal-like.
  - About 70% of basal-like tumors are triple-negative tumours are.
- Classic 'morphological clues' to a triple negative cancer usually refer to medullary carcinoma features.
- BCL11A overexpression recently identified as an oncogenic driver in this group ^[9]

Immunostains for typing and diagnosis

DCIS versus LCIS

Tabular comparison for DCIS versus LCIS:^[10]^[11]

Disease	E-cadherin	Beta-catenin	34betaE12	CAM5.2 (CK8)
DCIS	+ve	+ve	-ve	+ve peripheral cytoplasm
LCIS	-ve	-ve	+ve perinuclear	+ve perinuclear

Invasive versus non-invasive

Myoepithelial markers - typically lost in invasive carcinoma:^[12]

Stain	Location	Notes
p63	nuclear	up to 10% of invasive tumours +ve^[13]
Smooth muscle actin (SMA)	cytoplasmic	stains myofibroblasts & blood vessels
Calponin	cytoplasmic	stains myofibroblasts & blood vessels
Smooth muscle myosin heavy chain (SMM-HC)	cytoplasmic	stains myofibroblasts & blood vessels

Usual ductal hyperplasia versus ductal carcinoma in situ

Markers for UDH versus DCIS:^[13]

Disease	CK5/6	ER
UDH	diffuse +ve	patchy +ve
DCIS	-ve	diffuse +ve

Lymphovascular invasion

Main article: Lymphovascular invasion

D2-40 - marks the lymphatic spaces.^[14]^[15]
CD31 - marks lymphovascular spaces.
CD34 - marks lymphovascular spaces, less specific than CD31.

Treatment-related markers - overview

Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
- Sunnybrook uses CAM5.2.
ER (estrogen receptor).
- Positive in most breast cancers; +ve in ~75-80%.^[16]
PR (progesterone receptor).
- Positive in most breast cancers; +ve in ~65-70%.^[16]
HER2/neu (HER2).
- Usually negative; -ve in 70-80%.^[16]
- Positivity associated with a worse prognosis.
- In the context of HER2 positivity, PTEN/PI3K/Akt/mTOR pathway dysregulation is a poor prognosticator.^[17]^[18]

Note:

Male breast cancer is usually hormone receptor positive (~97%), and HER2 positivity is quite rare (~6%).^[19]

ER & PR scoring

Nuclear staining:^[16]

Give a percentage, i.e. 0-100%.
- Important cut points: 1% and 10%.
  - 0% = negative - not treated.
  - <10% = low positivity - treated.

Notes:

Normal breast epithelial cells have a patchy staining for ER and PR.
Evaluated on the invasive component.

HER2 scoring

Immunohistochemical based testing:^[20]^[21]

Score	Staining intensity	Cells stained (%)	Membrane staining	Management	Percentage of cases
0	no staining/barely visible	≤10%	incomplete	No HER2 blocker	~60%
1+	minimal/barely visible	>10%	incomplete	No HER2 blocker	~10%
2+	weak-to-moderate	>10%	incomplete (circumferential)	Needs SISH or FISH	~10% †
2+	intense	≤10%	complete	Needs SISH or FISH	~10% †
3+	intense staining	>10% ‡	complete	HER2 blocker	~20%

Note for IHC:

Normal breast epithelial cells do not stain with HER2.
Evaluated on the invasive component.
SISH = silver in situ hybridization.
FISH = fluorescence in situ hybridization.
† Together approximately 10%.
‡ The cut point was 10%, changed to 30% and then changed back to 10%.^[20]

ISH based testing:^[22]

Result	Ratio criteria	Gene copy number criteria
Positive	≥2.0 HER2/CEP17	≥6.0 copies of HER2/cell
Equivocal	<2.0 HER2/CEP17 (required)	4.0-6.0 copies of HER2/cell
Negative	<2.0 HER2/CEP17	<4.0 copies of HER2/cell

Note for ISH:

Can be called positive based on either ratio criteria or gene copy number criteria.

Clinical

ER & PR status determine whether a patient will get tamoxifen or other estrogen receptor modulators, such as raloxifene (Evista).
HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.

Characteristics of the subtypes

Invasive ductal carcinoma of the breast

AKA "NST" = No Specific Type.
AKA invasive mammary carcinoma.

Main article: Invasive ductal carcinoma of the breast

Invasive lobular carcinoma

Abbreviated ILC.
AKA lobular carcinoma.

Main article: Invasive lobular carcinoma

Medullary breast carcinoma

AKA medullary carcinoma of the breast.

Main article: Medullary breast carcinoma

Tubular carcinoma of the breast

AKA tubular carcinoma.

Main article: Tubular carcinoma of the breast

Metaplastic breast carcinoma

AKA metaplastic carcinoma.

Main article: Metaplastic breast carcinoma

Invasive micropapillary carcinoma of the breast

AKA micropapillary carcinoma.

General

Poor prognosis.
LVI common.^[23]

Microscopic

Features:

Clear spaces/clefting around (small) nests of tumour - diffuse/through-out the tumour - key feature.
- Described as "small clusters of tumour lying within dilated vascular channel-like spaces".^[24]

Note:

Ductal carcinoma commonly has clefting... but it isn't diffuse.

Images:

IHC

EMA +ve (periphery of nests); described as inside-out pattern.^[24]
E-cadherin +ve (centre of nests). (???)
p63 +ve/-ve.

Apocrine carcinoma of the breast

Main article: Apocrine carcinoma of the breast

Mucinous breast carcinoma

AKA mucinous carcinoma of the breast, AKA colloid carcinoma of the breast.

Main article: Mucinous breast carcinoma

Adenoid cystic carcinoma of the breast

AKA breast adenoid cystic carcinoma.

General

Like tumour of the salivary gland.
Very rare <0.1% of breast malignancies.^[26]
Good prognosis.^[26]

Microscopic

See: Adenoid cystic carcinoma article.

DDx:

Cribriform DCIS.
Collagenous spherulosis.

Images:

Adenoid cystic carcinoma of the breast (upmc.edu).

Invasive papillary carcinoma of the breast

AKA intracystic papillary carcinoma of the breast, abbreviated IPC.
AKA encapsulated papillary carcinoma of the breast, abbreviated EPC.

General

Very good prognosis^[27] - it is similar to DCIS.
Classical menopausal women.
~30% present with bloody discharge.^[28]

Microscopic

Features:

Lesion confined to a duct (intraductal) or cyst (intracystic).
- May have a thick fibrous capsule = encapsulated papillary carcinoma.^[28]
Loss of myoepithelial cells - key feature.
Neoplastic epithelial cells:
- Nuclear atypia - including: nucleoli, nuclear pleomorphism.
- Abnormal architecture - including cribriform, solid, micropapillary, papillary.

DDx:

Intraductal papilloma.

IHC

Loss of myoepithelial markers within the lesion.

Glycogen-rich clear cell carcinoma of the breast

Abbreviated GRCC.

Main article: Glycogen-rich clear cell carcinoma of the breast

Secretory carcinoma of the breast

AKA secretory breast carcinoma, abbreviated SBC.

Main article: Secretory carcinoma of the breast

Grading breast cancer

Most common system: Nottingham (aka Scarff-Bloom-Richardson) which is based on:

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.^[29] They also wrote a follow-up article in 2002.^[30]

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.^[31]

Staging breast cancer

Sentinel lymph node sampling in breast cancer

Main articles: Sentinel lymph node and 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.^[32]
- 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.^[33]

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.

Indictionas for lymph node sampling

Indications for lymph node sampling:^[34]

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:^[35]

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".^[35] 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:^[36]

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:^[37]^[38]

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

Main article: Lymphovascular invasion

In the context of breast pathology, the Rosen criteria for LVI are widely excepted, and are as follows:^[39]^[40]

Must be outside of the tumour proper.
- LVI is usually very close -- typically within 0.1 cm.
Contour of cells should differ from possible vessel wall.
- DCIS with retraction artifact mimicing LVI has a contour that matches its surrounding fibrous tissue.
Endothelium (usu. flat) should be visible.
Lymphatics are found adjacent to blood vessels - vessels should be present in the vicinity.

Memory device LUBE-O:

LVI has a Unique contour, Blood vessels and Endothelium in the vicinity, and is Outside of the tumour.

Note:

LVI does not affect the stage.

Other

Paget's disease

Main article: Paget disease of the breast

General

Associated with underlying breast carcinoma.^[41]

Notes:

Unrelated to Paget disease of the bone.

Microscopic

Features:^[41]

Cells in the epidermis:
- Epitheliod morphology (round/ovoid).
- Cells nested or single.
- Clear/pale cytoplasm key feature - may also be eosinophilic.
- Large nucleoli.

Images:

IHC & DDx:

See Paget disease.

Trivia

Tumour size and lymph node metastases

There is a paper^[42] that calculates the probability of lymph node mets based on tumour size. The developed formula is:

L_{To-Nodes}=1-exp(-Q_{n}D^{Z})

Where:

$L_{To-Nodes}$ = the probability of the lymph nodes being positive.
D = the largest dimension of the tumour in millimetres.
Z = 1.0041.
$Q_{n}$ = 0.019.

Selected values

Tumour size (mm)	Probability
5	9 %
10	17 %
15	25 %
20	32 %
25	38 %
30	44 %
35	49 %
40	54 %
45	58 %
50	62 %

Natural history

There is a theory that up to 22% of small (radiographically detected) breast tumours regress, based on an analysis in a large population.^[43] The study is supported by NCI's SEER data.^[44] Also, it generated many comments.^[43]

Missed macrometastases

The effect of missed macrometastases is small; this implies using IHC to look for isolated tumour cells is money that isn't well spent.^[45]

References

↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1143. ISBN 0-7216-0187-1.
↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html. Accessed on: 28 November 2010.
↑ URL: http://emedicine.medscape.com/article/1947145-overview. Accessed on: 24 August 2012.
↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 547. ISBN 978-1416054542.
↑ Tang, P.; Skinner, KA.; Hicks, DG. (Sep 2009). "Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready?". Diagn Mol Pathol 18 (3): 125-32. doi:10.1097/PDM.0b013e31818d107b. PMID 19704256.
↑ Curtis, C.; Shah, SP.; Chin, SF.; Turashvili, G.; Rueda, OM.; Dunning, MJ.; Speed, D.; Lynch, AG. et al. (Jun 2012). "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.". Nature 486 (7403): 346-52. doi:10.1038/nature10983. PMID 22522925.
↑ Badve, S.; Dabbs, DJ.; Schnitt, SJ.; Baehner, FL.; Decker, T.; Eusebi, V.; Fox, SB.; Ichihara, S. et al. (Feb 2011). "Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists.". Mod Pathol 24 (2): 157-67. doi:10.1038/modpathol.2010.200. PMID 21076464.
↑ Badve, S.; Dabbs, DJ.; Schnitt, SJ.; Baehner, FL.; Decker, T.; Eusebi, V.; Fox, SB.; Ichihara, S. et al. (Feb 2011). "Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists.". Mod Pathol 24 (2): 157-67. doi:10.1038/modpathol.2010.200. PMID 21076464.
↑ Khaled, WT.; Choon Lee, S.; Stingl, J.; Chen, X.; Raza Ali, H.; Rueda, OM.; Hadi, F.; Wang, J. et al. (2015). "BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells.". Nat Commun 6: 5987. doi:10.1038/ncomms6987. PMID 25574598.
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↑ Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 88. ISBN 978-0-323-06516-0.
↑ ^13.0 ^13.1 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 276. ISBN 978-0443066801.
↑ Ordóñez NG (March 2006). "Podoplanin: a novel diagnostic immunohistochemical marker". Adv Anat Pathol 13 (2): 83-8. doi:10.1097/01.pap.0000213007.48479.94. PMID 16670463.
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↑ Jensen, JD.; Knoop, A.; Laenkholm, AV.; Grauslund, M.; Jensen, MB.; Santoni-Rugiu, E.; Andersson, M.; Ewertz, M. (Dec 2011). "PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab.". Ann Oncol. doi:10.1093/annonc/mdr546. PMID 22172323.
↑ Schildhaus, HU.; Schroeder, L.; Merkelbach-Bruse, S.; Binot, E.; Büttner, R.; Kuhn, W.; Rudlowski, C. (Sep 2013). "Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes.". Breast. doi:10.1016/j.breast.2013.08.008. PMID 24080492.
↑ ^20.0 ^20.1 Rakha, EA.; Starczynski, J.; Lee, AH.; Ellis, IO. (Apr 2014). "The updated ASCO/CAP guideline recommendations for HER2 testing in the management of invasive breast cancer: a critical review of their implications for routine practice.". Histopathology 64 (5): 609-15. doi:10.1111/his.12357. PMID 24382093.
↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf. Accessed on: October 7, 2014.
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↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 2 April 2012.
↑ ^35.0 ^35.1 URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
↑ URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
↑ URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
↑ URL: http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging. Accessed on: 9 July 2010.
↑ Rosen, PP. (1983). "Tumor emboli in intramammary lymphatics in breast carcinoma: pathologic criteria for diagnosis and clinical significance.". Pathol Annu 18 Pt 2: 215-32. PMID 6674861.
↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 5 August 2011.
↑ ^41.0 ^41.1 URL: http://emedicine.medscape.com/article/1101235-diagnosis
↑ Porembka, MR.; Abraham, RL.; Sefko, JA.; Deshpande, AD.; Jeffe, DB.; Margenthaler, JA. (Oct 2008). "Factors associated with lymph node assessment in ductal carcinoma in situ: analysis of 1988-2002 seer data.". Ann Surg Oncol 15 (10): 2709-19. doi:10.1245/s10434-008-9947-5. PMID 18483831. http://onlinelibrary.wiley.com/doi/10.1002/cncr.24592/pdf.
↑ ^43.0 ^43.1 Zahl, PH.; Maehlen, J.; Welch, HG. (Nov 2008). "The natural history of invasive breast cancers detected by screening mammography.". Arch Intern Med 168 (21): 2311-6. doi:10.1001/archinte.168.21.2311. PMID 19029493.
↑ Jatoi, I.; Anderson, WF. (May 2009). "Breast cancer overdiagnosis with screening mammography.". Arch Intern Med 169 (10): 999-1000, author reply 1000-1. doi:10.1001/archinternmed.2009.95. PMID 19468099.
↑ Weaver, DL.; Ashikaga, T.; Krag, DN.; Skelly, JM.; Anderson, SJ.; Harlow, SP.; Julian, TB.; Mamounas, EP. et al. (Feb 2011). "Effect of occult metastases on survival in node-negative breast cancer.". N Engl J Med 364 (5): 412-21. doi:10.1056/NEJMoa1008108. PMID 21247310.

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[Ref_PCPBoD8_547-4] Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 547. ISBN 978-1416054542.

[pmid19704256-5] Tang, P.; Skinner, KA.; Hicks, DG. (Sep 2009). "Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready?". Diagn Mol Pathol 18 (3): 125-32. doi:10.1097/PDM.0b013e31818d107b. PMID 19704256.

[6] Curtis, C.; Shah, SP.; Chin, SF.; Turashvili, G.; Rueda, OM.; Dunning, MJ.; Speed, D.; Lynch, AG. et al. (Jun 2012). "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.". Nature 486 (7403): 346-52. doi:10.1038/nature10983. PMID 22522925.

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[8] Badve, S.; Dabbs, DJ.; Schnitt, SJ.; Baehner, FL.; Decker, T.; Eusebi, V.; Fox, SB.; Ichihara, S. et al. (Feb 2011). "Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists.". Mod Pathol 24 (2): 157-67. doi:10.1038/modpathol.2010.200. PMID 21076464.

[9] Khaled, WT.; Choon Lee, S.; Stingl, J.; Chen, X.; Raza Ali, H.; Rueda, OM.; Hadi, F.; Wang, J. et al. (2015). "BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells.". Nat Commun 6: 5987. doi:10.1038/ncomms6987. PMID 25574598.

[Ref_BP275-10] O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 275. ISBN 978-0443066801.

[pmid18318578-11] Yeh IT, Mies C (March 2008). "Application of immunohistochemistry to breast lesions". Arch. Pathol. Lab. Med. 132 (3): 349-58. PMID 18318578. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349.

[12] Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 88. ISBN 978-0-323-06516-0.

[Ref_BP276-13] 13.0 ^13.1 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 276. ISBN 978-0443066801.

[14] Ordóñez NG (March 2006). "Podoplanin: a novel diagnostic immunohistochemical marker". Adv Anat Pathol 13 (2): 83-8. doi:10.1097/01.pap.0000213007.48479.94. PMID 16670463.

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[pmid22454081-17] Gallardo, A.; Lerma, E.; Escuin, D.; Tibau, A.; Muñoz, J.; Ojeda, B.; Barnadas, A.; Adrover, E. et al. (Apr 2012). "Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas.". Br J Cancer 106 (8): 1367-73. doi:10.1038/bjc.2012.85. PMID 22454081.

[pmid22172323-18] Jensen, JD.; Knoop, A.; Laenkholm, AV.; Grauslund, M.; Jensen, MB.; Santoni-Rugiu, E.; Andersson, M.; Ewertz, M. (Dec 2011). "PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab.". Ann Oncol. doi:10.1093/annonc/mdr546. PMID 22172323.

[pmid24080492-19] Schildhaus, HU.; Schroeder, L.; Merkelbach-Bruse, S.; Binot, E.; Büttner, R.; Kuhn, W.; Rudlowski, C. (Sep 2013). "Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes.". Breast. doi:10.1016/j.breast.2013.08.008. PMID 24080492.

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[21] URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf. Accessed on: October 7, 2014.

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[pmid20304650-23] Yu, JI.; Choi, DH.; Park, W.; Huh, SJ.; Cho, EY.; Lim, YH.; Ahn, JS.; Yang, JH. et al. (Jun 2010). "Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: matched case-control study.". Breast 19 (3): 231-7. doi:10.1016/j.breast.2010.01.020. PMID 20304650.

[pmid20444748-24] 24.0 ^24.1 Yamaguchi, R.; Tanaka, M.; Kondo, K.; Yokoyama, T.; Kaneko, Y.; Yamaguchi, M.; Ogata, Y.; Nakashima, O. et al. (Aug 2010). "Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis.". Jpn J Clin Oncol 40 (8): 781-7. doi:10.1093/jjco/hyq056. PMID 20444748.

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[31] MUA. 20 January 2009.

[32] Giuliano AE, Hunt KK, Ballman KV, et al. (February 2011). "Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial". JAMA 305 (6): 569–75. doi:10.1001/jama.2011.90. PMID 21304082.

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[34] URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 2 April 2012.

[acs_website-35] 35.0 ^35.1 URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.

[36] URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.

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[40] URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 5 August 2011.

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[pmid18483831-42] Porembka, MR.; Abraham, RL.; Sefko, JA.; Deshpande, AD.; Jeffe, DB.; Margenthaler, JA. (Oct 2008). "Factors associated with lymph node assessment in ductal carcinoma in situ: analysis of 1988-2002 seer data.". Ann Surg Oncol 15 (10): 2709-19. doi:10.1245/s10434-008-9947-5. PMID 18483831. http://onlinelibrary.wiley.com/doi/10.1002/cncr.24592/pdf.

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@@ Line 156: / Line 156: @@
 *Overview
+**A category of breast carcinomas defined by gene expression profiling
 **Somewhere between 15-30% of breast carcinomas.
-**A category of breast carcinomas defined by gene expression profiling
 **Can be identified by immunohistochemistry - basal markers (CK14, p63, calponin, SMA)
 **Not derived from myoepithelial cells, merely express a phenotype more in keeping with basal cells than ductal cells
@@ Line 188: / Line 188: @@
 **Basal-like breast cancer is a heterogeneous group.
 **The behaviour of basal-like breast cancer appears to fall into two groups:
-***The tumours that do not metastasise have a better prognosis than other types of breast carcinoma.
+***The tumours that are by nature low grade (ie adenoid cystic carcinoma) and/or do not metastasise have a better prognosis than other types of breast carcinoma.
-***Tumours with early metastasis may behave more aggressively
+***The tumours with early metastasis that may behave more aggressively
-****Hematogenous spread -greater tendency to metastasise to visceral sites associated with poorer prognosis (such as lung and brain)  instead of to nodes and bone.
+****Hematogenous spread -greater tendency to metastasise to visceral sites (notably lung and brain) instead of to nodes and bone.
 **Many have a complete response to chemotherapy and survival rates similar to typical breast cancer
 **Non-complete response to chemotherapy is associated with low survival at 5 years.

Difference between revisions of "Invasive breast cancer"

Revision as of 11:41, 20 March 2015

Introduction

Overview of invasive breast cancer subtypes

Common epithelial subtypes

Common stromal types

Good prognosis subtypes

Comprehensive list of invasive breast cancer subtypes

Epithelial

Myoepithelial

Mesenchymal tumours

Fibroepithelial tumours

Nipple lesions

Other

Familial breast cancer

Breast IHC

Molecular classification of invasive carcinoma

Immunostains for typing and diagnosis

DCIS versus LCIS

Invasive versus non-invasive

Usual ductal hyperplasia versus ductal carcinoma in situ

Lymphovascular invasion

Treatment-related markers - overview

ER & PR scoring

HER2 scoring

Clinical

Characteristics of the subtypes

Invasive ductal carcinoma of the breast

Invasive lobular carcinoma

Medullary breast carcinoma

Tubular carcinoma of the breast

Metaplastic breast carcinoma

Invasive micropapillary carcinoma of the breast

General

Microscopic

IHC

Apocrine carcinoma of the breast

Mucinous breast carcinoma

Adenoid cystic carcinoma of the breast

General

Microscopic

Invasive papillary carcinoma of the breast

General

Microscopic

IHC

Glycogen-rich clear cell carcinoma of the breast

Secretory carcinoma of the breast

Grading breast cancer

Note about mitosis counting

Calculating Nottingham score

Staging breast cancer

Sentinel lymph node sampling in breast cancer

General

Microscopic

IHC

N stage

Indictionas for lymph node sampling

Definitions

Details

T stage

M stage

Lymphovascular invasion

Other

Paget's disease

General

Microscopic

Trivia

Tumour size and lymph node metastases

Selected values

Natural history

Missed macrometastases

See also

References

External links

Navigation menu

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