Breast cancer classification: Difference between revisions

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{{Breast cancer}}
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{{CMG}} {{AE}} {{MGS}}
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==Overview==
==Overview==
 
Breast cancer may be classified according to anatomy into 4 subtypes: ductal, lobular, sarcoma, and lymphoma. There are also other methods of classification such as classification based on gene expression, and classification based on hormone receptors present. In practice, a combination of all above mentioned classification is combined with the surgical characteristics of tumors and radiologic findings is being applied for patient management, treatment planning, and prognosis determination.
==Classification Based on Histopathology==
==Classification based on histopathology==
===Malignant Tumors===
===Malignant Tumors===
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'''Ductal'''
'''Ductal'''
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*[[Ductal carcinoma in situ]] (DCIS)<ref name = class> Breast Neoplasm. Radiopedia. (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on January 16, 2016</ref>
*[[Ductal carcinoma in situ]] (DCIS)<ref name="class">Breast Neoplasm. Radiopedia. (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on March 1, 2019</ref>
:*Comedo type: ~60%  
:*Comedo type: ~60%  
:*Non-comedo type: ~40%
:*Non-comedo type: ~40%
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::*Cribriform
::*Cribriform
::*Solid
::*Solid
:*Intracystic papillary carcinoma in situ
:*Intracystic papillary [[carcinoma]] in situ
*Invasive ductal carcinoma
*Invasive ductal [[carcinoma]]
:*Invasive ductal carcinoma not otherwise specified (NOS): ~65%
:*Invasive ductal [[carcinoma]] not otherwise specified (NOS): ~65%
:*Tubular carcinoma of breast: ~7-8%
:*Tubular[[carcinoma]] of breast: ~7-8%
::*Tubulolobular carcinoma of breast
::*Tubulolobular [[carcinoma]]<nowiki/>of breast
:*Medullary carcinoma of breast: ~2%
:*Medullary[[carcinoma]] of breast: ~2%
:*Mucinous (colloid) carcinoma: ~2%
:*Mucinous (colloid) carcinoma: ~2%
:*Malignant papillary lesions of the breast
:*Malignant papillary lesions of the breast
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*Apocrine carcinoma of the breast
*Apocrine carcinoma of the breast
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'''Sarcoma'''
'''Sarcoma'''
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===Benign Tumors===
===Benign Tumors===
*[[Phyllodes tumor]]<ref name = class> Breast Neoplasms. Radiopaedia (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on january 16, 2016 </ref>
*[[Phyllodes tumor]]<ref name="class">Breast Neoplasms. Radiopaedia (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on january 16, 2016 </ref>
*Mammary fibromatosis: 0.2% of all breast tumors 5
*Mammary fibromatosis: 0.2% of all breast tumors 5
*Benign papillary lesions of the breast
*Benign papillary lesions of the breast
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*Granular cell tumor of the breast
*Granular cell tumor of the breast


==Classification Based on Hormone Receptors Present==
==Classification based on hormone receptors present==
*'''Hormone receptor positive''': either estrogen or progesterone receptors are present
*'''Hormone receptor positive''': either estrogen or progesterone receptors are present
*'''Hormone receptor negative''': breast cancer cells don’t have either estrogen or progesterone receptors
*'''Hormone receptor negative''': breast cancer cells do not have either estrogen or progesterone receptors
*'''HER2 positive''': If excess copies of HER2 gene
*'''[[HER2]] positive''': If excess copies of [[HER2|HER2 gene]]
*'''HER2 negative''': If excess copies of HER2 gene are not present
*'''[[HER2]] negative''': If excess copies of [[HER2|HER2 gene]] are not present
*'''Triple positive''': cancers that are ER-positive, PR-positive, and have too much HER2
*'''Triple positive''': cancers that are [[Estrogen receptor|ER]]-positive, PR-positive, and have too much HER2
*'''Triple negative''': If the breast cancer cells don’t have estrogen or progesterone receptors and don’t have too much HER2
*'''Triple negative''': If the breast cancer cells don not have estrogen or progesterone receptors and don’t have too much HER2


==Classification Based on Gene Expression==
==Classification based on gene expression==
*'''Luminal type''': are estrogen receptor (ER)–positive
*'''Luminal type''': are estrogen receptor (ER)–positive
:*'''Luminal A''':  
 
:*'''Luminal A''':
::*Expression of luminal (low molecular weight) [[Cytokeratin|cytokeratins]], high expression of [[hormone receptor]]<nowiki/>s and related [[Gene|genes]]
::*50% of invasive bresat cancer, [[Estrogen receptor|ER]]/[[Progesterone receptor|PR]] positive, [[HER2/neu]] negative
::*Tubular carcinoma, Cribriform [[carcinoma]], Low grade invasive ductal [[carcinoma]], NOS, Classic lobular[[carcinoma]]
::*Response to endocrine therapy
::*Variable response to chemotherapy
::*Low grade,
::*Low grade,
::*Grows slowly,
::*Grows slowly,
::*Have the best prognosis
::*Good prognosis (the best prognosis)
:*'''Luminal B''':
:*'''Luminal B :'''
::*Expression of luminal (low molecular weight) cytokeratins, moderate-low expression of hormone receptors and related genes
::*20% of invasive breast cancer, ER/PR positive, [[HER2/neu]] expression variable, higher proliferation than Luminal A, higher histologic grade than Luminal A
::*Invasive ductal [[carcinoma]], NOS Micropapillary [[carcinoma]]
::*Response to endocrine therapy (tamoxifene and aromatase inhibitors) not as good as Luminal A
::*Variable response to chemotherapy (better than Luminal A)
::*Prognosis not as good as Luminal A
::*Grows faster
::*Grows faster
::*Have bad prognosis
:*'''HER2/neu'''
 
::*High expression of [[HER2/neu]], low expression of ER and related genes
==Staging==
::*15% of invasive breast cancer, ER/PR negative, [[HER2/neu]] positive, high proliferation, diffuse [[TP53]] mutation, high histologic grade and nodal positivity
The breast cancer stage is based on the results of testing that is done on the tumor and lymph nodes removed during surgery and other tests.<ref name = stage> Breast Cancer. National Cancer Institute (2016) http://www.cancer.gov/types/breast/patient/breast-treatment-pdq#link/_148 Accessed on January 16, 2016 </ref>
::*High grade invasive ductal carcinoma, NOS
===Stage 0===
::*Response to [[trastuzumab]] [[Trastuzumab|(Herceptin]])
There are 3 types of breast [[carcinoma in situ]]:
::*Response to chemotherapy with antracyclins
*[[Ductal carcinoma in situ]] (DCIS)
::*Usually unfavorable prognosis
:*Noninvasive condition in which abnormal cells are found in the lining of a breast duct
:*'''Basal like'''
:*Abnormal cells have not spread outside the duct to other tissues in the breast
::*High expression of basal epithelial genes and basal cytokeratins, low expression of ER and related genes, low expression of HER2/neu
:*May become invasive cancer and spread to other tissues
::*~15% of invasive breast cancer, most [[Estrogen receptor|ER]]/[[Progesterone receptor|PR]], [[HER2/neu]] negative (triple negative), high proliferation, diffuse [[TP53]] mutation, BRCA1 dysfunction (germline, sporadi
*[[Lobular carcinoma in situ]] (LCIS)
::*High grade invasive ductal [[carcinoma]], NOS Metaplastic [[carcinoma]], Medullary carcinoma
:*Abnormal cells are found in the lobules of the breast
::*No response to endocrine therapy or trastuzumab
:*This condition seldomly becomes invasive
::*Sensitive to platinum group chemotherapy and PARP inhibitors
*[[Paget's disease of the nipple]]  
::*Not all, but usually worse prognosis<ref name="pmid28331693">Eliyatkın N, Yalçın E, Zengel B, Aktaş S, Vardar E (2015) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=28331693 Molecular Classification of Breast Carcinoma: From Traditional, Old-Fashioned Way to A New Age, and A New Way.] ''J Breast Health'' 11 (2):59-66. [http://dx.doi.org/10.5152/tjbh.2015.1669 DOI:10.5152/tjbh.2015.1669] PMID: [https://pubmed.gov/28331693 28331693]</ref>
:*Abnormal cells are found in the nipple only
===Stage 1===
*Cancer has formed
*Stage I is divided into stages IA and IB
*'''Stage IA''':  
:*Tumor is < 2 centimeters
:*Cancer has not spread outside the breast
*'''Stage IB''':  
:*Small clusters of breast cancer cells (0.2 mm - 2 mm) are found in the lymph nodes and either:
:*no tumor is found in the breast; or
:*Numor is < 2 centimeters
 
===Stage II===
Stage II is divided into stages IIA and IIB.
*In stage IIA:
:*no tumor is found in the breast or the tumor is 2 centimeters or smaller. Cancer (larger than 2 millimeters) is found in 1 to 3 axillary lymph nodes or in the lymph nodes near the breastbone (found during a sentinel lymph node biopsy); or
:*the tumor is larger than 2 centimeters but not larger than 5 centimeters. Cancer has not spread to the lymph nodes.
*In stage IIB, the tumor is:
:*larger than 2 centimeters but not larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes; or
:*larger than 2 centimeters but not larger than 5 centimeters. Cancer has spread to 1 to 3 axillary lymph nodes or to the lymph nodes near the breastbone (found during a sentinel lymph node biopsy); or
:*larger than 5 centimeters. Cancer has not spread to the lymph nodes.
===Stage III===
Stage III is divided into IIIA, IIIB, and IIIC.
*Stage IIIA
:*no tumor is found in the breast or the tumor may be any size. Cancer is found in 4 to 9 axillary lymph nodes or in the lymph nodes near the breastbone (found during imaging tests or a physical exam); or
:*the tumor is larger than 5 centimeters. Small clusters of breast cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes; or
:*the tumor is larger than 5 centimeters. Cancer has spread to 1 to 3 axillary lymph nodes or to the lymph nodes near the breastbone (found during a sentinel lymph node biopsy).
*Stage IIIB
:*the tumor may be any size and cancer has spread to the chest wall and/or to the skin of the breast and caused swelling or an ulcer.
:*cancer may have spread to:
::*up to 9 axillary lymph nodes; or
::*the lymph nodes near the breastbone
*Stage IIIC
:*no tumor is found in the breast or the tumor may be any size. Cancer may have spread to the skin of the breast and caused swelling or an ulcer and/or has spread to the chest wall.
:*cancer has spread to:
::*10 or more axillary lymph nodes; or
::*lymph nodes above or below the collarbone; or
::*axillary lymph nodes and lymph nodes near the breastbone
:*For treatment, stage IIIC breast cancer is divided into operable and inoperable stage IIIC.
===Stage IV===
*In stage IV, cancer has spread to other organs of the body, most often the bones, lungs, liver, or brain.
 
===Inflammatory Breast Cancer===
*In inflammatory breast cancer, cancer has spread to the skin of the breast and the breast looks red and swollen and feels warm. The redness and warmth occur because the cancer cells block the lymph vessels in the skin. The skin of the breast may also show the dimpled appearance called peau d’orange (like the skin of an orange). There may not be any lumps in the breast that can be felt.
*Inflammatory breast cancer may be stage IIIB, stage IIIC, or stage IV.
 
 
[[Tumor|'''T'''umor]] - There are five tumor classification values (Tis, T1, T2, T3 or T4) which depend on the presence or absence of invasive cancer, the dimensions of the invasive cancer, and the presence or absence of invasion outside of the breast (e.g. to the skin of the breast, to the muscle, or to the rib cage underneath):
*Tx - Primary tumor cannot be assessed
*T0 - No evidence of primary tumor
*Tis - Carcinoma in situ
** Tis([[Ductal carcinoma|DCIS]]) - Intraductal Carcinoma in situ
** Tis(LCIS) - Lobular Carcinoma in situ
** Tis(Paget's) - [[Paget's disease of the breast|Paget's disease]] of the nipple with no tumor
* T1 - Tumor 2cm or less in its greatest dimension
** T1mic - Microinvasion 0.1cm or less in greatest dimension
** T1a - Tumor more than 0.1cm but not more than 0.5cm in its greatest dimension
** T1b - Tumor more than 0.5cm but not more than 1.0cm in its greatest dimension
** T1c - Tumor more than 1.0cm but not more than 2.0cm in its greatest dimension
*T2 - Tumor more than 2.0cm but not more than 5.0cm in its greatest dimension
*T3 - Tumor more than 5cm in its greatest dimension
*T4 - Tumor of any size with direct extension to (a) chest wall or (b) skin as described below:
** T4a - Extension to chest wall
** T4b - [[Edema]] (including [[peau d'orange]]) or ulceration of the breast skin, or satellite skin nodules confined to the same breast
** T4c - Both T4a and T4b
** T4d - [[Inflammatory breast cancer]]
 
[[lymph node|Lymph '''N'''ode]] - There are four lymph node classification values (N0, N1, N2 or N3) which depend on the number, size, and location of breast cancer cell deposits in lymph nodes.
* Nx - regional lymph nodes cannot be assessed, perhaps due to previous removal
* N0 - no regional lymph node metastasis
* N1 - metastasis to movable regional axillary lymph nodes on the same side as the affected breast
* N2 - metastasis to fixed regional axillary lymph nodes, or metastasis to the internal mammary lymph nodes, on the same side as the affected breast
* N3 - metastasis to supraclavicular lymph nodes or infraclavicular lymph nodes or metastasis to the internal mammary lymph nodes with metastasis to the axillary lymph nodes
 
[[Metastasis|'''M'''etastases]] - There are two metastatic classification values (M0 or M1) which depend on the presence or absence of breast cancer cells in locations other than the breast and lymph nodes (so-called distant metastases, e.g. to bone, brain, lung).
 
==Grading==
Grading is a way of classifying breast cancer cells based on their appearance and behaviour when viewed under a microscope.
The most common grading system for breast cancer is the Nottingham modification of the Bloom-Richardson scale (may also be called the Scarff-Bloom-Richardson or the Elson-Ellis grade). It is used for invasive breast cancers.
This grading system is based on 3 different features of the cells in the tumor. Each of these features is given a score of 1 to 3.<ref name = grade> Breast Cancer. Canadian Cancer society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/breast/grading/?region=on#ixzz3xSTfYblf Accessed on January 16, 2016</ref>
*Tubule formation – the percentage of the tumor that is made up of tubular structures
:*1 – The tumor is made up of more than 75% tubules.
:*2 – The tumor is made up of 10%–75% tubules.
:*3 – The tumor is made up of less than 10% tubules.
*Nuclear pleomorphism – the degree of change in the size and shape of the tumor cells’ nuclei (the part of the cell that holds the chromosomes, which contain genetic information)
:*1 – The nuclei are small and uniform in size and shape.
:*2 – The nuclei are medium to large in size, but are mostly the same size and shape.
:*3 – The nuclei are large and vary in size and shape.
*Mitotic count – the number of cells that are actively dividing
:*1 – The tumor cells are dividing at a slow rate.
:*2 – The tumor cells are dividing at a moderate rate.
:*3 – The tumor cells are dividing at a fast rate.
The individual scores from these 3 features are added together to give a total score between 3 and 9. A tumor grade is then assigned based on the total score.
'''Bloom-Richardson Grade – Nottingham modification'''
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'''I'''
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3-5
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Low-grade (well-differentiated) tumors that do not appear to be growing quickly and are less likely to spread
|-
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'''II'''
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6-7
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Intermediate-grade (moderately differentiated) tumors that have features between grade 1 and 3
|-
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'''III'''
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8-9
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High-grade (poorly differentiated) tumors that tend to grow faster and are more likely to spread
|-
 
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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Latest revision as of 20:00, 12 December 2019

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

Overview

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

Classification based on histopathology

Malignant Tumors
Type Subtype

Ductal

  • Comedo type: ~60%
  • Non-comedo type: ~40%
  • Papillary
  • Micropapillary
  • Cribriform
  • Solid
  • Invasive ductal carcinoma not otherwise specified (NOS): ~65%
  • Tubularcarcinoma of breast: ~7-8%
  • Medullarycarcinoma of breast: ~2%
  • Mucinous (colloid) carcinoma: ~2%
  • Malignant papillary lesions of the breast
  • Papillary carcinoma of breast: 1-2% 1

Lobular

Other malignant breast tumors

Sarcoma

Lymphoma

Metastases to the breast

The most common extra-mammary cancers that metastasise to breast are:

Benign Tumors

  • Phyllodes tumor[1]
  • Mammary fibromatosis: 0.2% of all breast tumors 5
  • Benign papillary lesions of the breast
  • Intraductal papilloma
  • Solitary papilloma of breast
  • Central solitary papilloma of breast
  • Peripheral solitary papilloma of breast
  • Multiple papillomata of breast
  • Juvenile papillomatosis of breast
  • Granular cell tumor of the breast

Classification based on hormone receptors present

  • Hormone receptor positive: either estrogen or progesterone receptors are present
  • Hormone receptor negative: breast cancer cells do not have either estrogen or progesterone receptors
  • HER2 positive: If excess copies of HER2 gene
  • HER2 negative: If excess copies of HER2 gene are not present
  • Triple positive: cancers that are ER-positive, PR-positive, and have too much HER2
  • Triple negative: If the breast cancer cells don not have estrogen or progesterone receptors and don’t have too much HER2

Classification based on gene expression

  • Luminal type: are estrogen receptor (ER)–positive
  • Luminal A:
  • Expression of luminal (low molecular weight) cytokeratins, high expression of hormone receptors and related genes
  • 50% of invasive bresat cancer, ER/PR positive, HER2/neu negative
  • Tubular carcinoma, Cribriform carcinoma, Low grade invasive ductal carcinoma, NOS, Classic lobularcarcinoma
  • Response to endocrine therapy
  • Variable response to chemotherapy
  • Low grade,
  • Grows slowly,
  • Good prognosis (the best prognosis)
  • Luminal B :
  • Expression of luminal (low molecular weight) cytokeratins, moderate-low expression of hormone receptors and related genes
  • 20% of invasive breast cancer, ER/PR positive, HER2/neu expression variable, higher proliferation than Luminal A, higher histologic grade than Luminal A
  • Invasive ductal carcinoma, NOS Micropapillary carcinoma
  • Response to endocrine therapy (tamoxifene and aromatase inhibitors) not as good as Luminal A
  • Variable response to chemotherapy (better than Luminal A)
  • Prognosis not as good as Luminal A
  • Grows faster
  • HER2/neu
  • High expression of HER2/neu, low expression of ER and related genes
  • 15% of invasive breast cancer, ER/PR negative, HER2/neu positive, high proliferation, diffuse TP53 mutation, high histologic grade and nodal positivity
  • High grade invasive ductal carcinoma, NOS
  • Response to trastuzumab (Herceptin)
  • Response to chemotherapy with antracyclins
  • Usually unfavorable prognosis
  • Basal like
  • High expression of basal epithelial genes and basal cytokeratins, low expression of ER and related genes, low expression of HER2/neu
  • ~15% of invasive breast cancer, most ER/PR, HER2/neu negative (triple negative), high proliferation, diffuse TP53 mutation, BRCA1 dysfunction (germline, sporadi
  • High grade invasive ductal carcinoma, NOS Metaplastic carcinoma, Medullary carcinoma
  • No response to endocrine therapy or trastuzumab
  • Sensitive to platinum group chemotherapy and PARP inhibitors
  • Not all, but usually worse prognosis[2]

References

  1. ↑ 1.0 1.1 Breast Neoplasm. Radiopedia. (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on March 1, 2019
  2. ↑ Eliyatkın N, Yalçın E, Zengel B, Aktaş S, Vardar E (2015) Molecular Classification of Breast Carcinoma: From Traditional, Old-Fashioned Way to A New Age, and A New Way. J Breast Health 11 (2):59-66. DOI:10.5152/tjbh.2015.1669 PMID: 28331693

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