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==Overview==
==Overview==
'''Breast cancer classification''' divides all forms of [[breast cancer]] according to four different schemes, each based on different criteria and serving a different purpose.  The four approaches consider pathology, the grade of the tumor, expression of proteins and genes, and the stage of the tumor in order to distinguish the form of breast cancer.


Classifications of breast cancer are usually, but not always, classified by the histological appearance of tissue in the tumor.  Rare variants are defined on the basis of [[physical exam]] findings. For example, [[Inflammatory breast cancer]] (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other [[carcinoma]]s by the [[inflammation|inflamed]] appearance of the affected breast.<ref>{{cite journal |author=Giordano SH, Hortobagyi GN |title=Inflammatory breast cancer: clinical progress and the main problems that must be addressed |journal=Breast Cancer Res. |volume=5 |issue=6 |pages=284–8 |year=2003 |pmid=14580242 |doi=10.1186/bcr608}} [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14580242 Free Full Text].</ref> In the future, some pathologic classifications may change. For example, a subset of ductal carcinomas may be re-named [[basal-like carcinoma]] (part of the [[Triple Negative Breast Cancer|"triple-negative" tumors]]).
==Classification Based on Histopathology==
 
===Malignant Tumors===
==Major Schemes==
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
*[[Pathology]] - A [[surgical pathology|pathologist]] will categorize each tumor based on its [[Histology|histological]] (microscopic anatomy) appearance and other criteria. The most common pathologic types of breast cancer are: invasive [[ductal carcinoma]], [[malignant]] cancer in the breast's [[Duct (anatomy)|ducts]]; and invasive lobular carcinoma, malignant cancer in the breast's [[Lobe (anatomy)|lobules]].
|valign=top|
*[[Bloom-Richardson grade|Grade of tumor]] - The histological grade of a [[tumor]] is determined by a pathologist under a microscope. A ''well-differentiated'' (low grade) tumor resembles normal tissue. A ''poorly differentiated'' (high grade) tumor is composed of disorganized cells and, therefore, does not look like normal tissue. ''Moderately differentiated'' (intermediate grade) tumors are somewhere in between.
|+
*[[Protein expression|Protein]] & [[gene expression]] status - Currently, all breast cancers should be tested for expression, or detectable effect, of the [[estrogen receptor]] (ER), [[progesterone receptor]] (PR), and [[HER2/neu]] proteins. These tests are usually done by [[immunohistochemistry]] and are presented in a pathologist's report. The profile of expression of a given tumor helps predict its [[prognosis]], or outlook, and helps an [[oncology|oncologist]] choose the most appropriate treatment. More genes and/or proteins may be tested in the future (eg [[PAX2]]<ref>http://cordis.europa.eu/fetch?CALLER=EN_NEWS&ACTION=D&SESSION=&RCN=30093</ref>).
! style="background: #4479BA; width: 150px;" | {{fontcolor|#FFF|Type}}
*Stage of a tumor - The currently accepted staging scheme for breast cancer is the [[TNM classification]].
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Subtype}}
 
|-
<br clear="left">
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
[[Image:BCtimeline.jpg|thumb|left|450px|Time line of breast cancer suggesting probable [[heterogeneity]]. Primary breast cancers begin as single (or more) cells which have lost normal regulation of differentiation and proliferation but remain confined within the [[basement membrane]] of the [[duct]] or [[lobule]]. As these cells go through several doublings, at some point they invade through the [[basement membrane]] of the [[duct]] or [[lobule]] and ultimately [[metastasize]] to distant organs.]]
'''Adenocarcinoma'''<ref name = class> Breast Neoplasm. Radiopedia. (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on January 16, 2016</ref>
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Ductal'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*Ductal carcinoma in situ (DCIS)
:*comedo type: ~60% of DCIS
:*non comedo type: ~40% of DCIS
::*papillary
::*micropapillary
::*cribriform
::*solid
:*intracystic papillary carcinoma in situ
*'''invasive ductal carcinoma'''
:*invasive ductal carcinoma not otherwise specified (NOS): ~65%
:*tubular carcinoma of breast: ~7-8%
::*tubulolobular carcinoma of breast
:*medullary carcinoma of breast (MCB): ~2%
:*mucinous (colloid) carcinoma: ~2%
:*malignant papillary lesions of the breast
::*papillary carcinoma of breast: 1-2% 1
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Lobular'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*lobular carcinoma in situ (LCIS)
*invasive lobular carcinoma: ~10%
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Other malignant breast tumors'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*inflammatory carcinoma of breast: 1-4%
*Paget disease of the nipple
*triple negative and basal-like breast cancers
*metaplastic carcinoma of the breast
*adenoid cystic carcinoma of the breast: <0.4%
*apocrine carcinoma of the breast
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Sarcoma'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*angiosarcoma of the breast
*fibrosarcoma of breast
*extra-skeletal osteosarcoma of breast
*malignant phyllodes tumor
*angiosarcoma
*rhabdomyosarcoma
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Lymphoma'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*Non-hodgkin lymphoma
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Metastases to the breast'''
| style="padding: 5px 5px; background: #F5F5F5;" |
The most common extra-mammary cancers that metastasise to breast are:
*[[lymphoma]]/[[leukaemia]]: most common extra mammary source
*[[melanoma]]
*[[sarcomas]]
*[[prostate cancer]]: considered on the most frequent primary sites in men 4
*[[lung cancer]]
*[[gastric cancer]]
*[[ovarian cancer]]
*[[renal cell cancer]]
|-
|}
===Benign Tumors===
*Phyllodes tumor<ref name = ben> Breast Neoplasms. Radiopaedia (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on january 16, 2016 </ref>
*mammary fibromatosis: 0.2% of all breast tumours 5
*benign papillary lesions of the breast
:*papilloma
::*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 tumour of the breast


==Staging==
==Staging==
 
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>
==Staging==
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.
===Stage 0===
===Stage 0===
There are 3 types of breast carcinoma in situ:
There are 3 types of breast carcinoma in situ:
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*Paget disease of the nipple is a condition in which abnormal cells are found in the nipple only.
*Paget disease of the nipple is a condition in which abnormal cells are found in the nipple only.
===Stage 1===
===Stage 1===
In stage I, cancer has formed. Stage I is divided into stages IA and IB.<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>
In stage I, cancer has formed. Stage I is divided into stages IA and IB.
*In stage IA, the tumor is 2 centimeters or smaller. Cancer has not spread outside the breast.
*In stage IA, the tumor is 2 centimeters or smaller. Cancer has not spread outside the breast.
*In stage IB, small clusters of breast cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes and either:
*In stage IB, small clusters of breast cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes and either:
:*no tumor is found in the breast; or
:*no tumor is found in the breast; or
:*the tumor is 2 centimeters or smaller.
:*the tumor is 2 centimeters or smaller.
===Stage II===
===Stage II===
Stage II is divided into stages IIA and IIB.
Stage II is divided into stages IIA and IIB.
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[[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).
[[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).
==Pathologic Types==
''''Note: The following list includes benign tumors (non cancers) as well as malignant tumors (cancers)''''
The latest (2003) [[World Health Organization]] (WHO)  classification of tumors of the breast<ref>''Tumours of the breast and female genital organs'', WHO classification of tumours, 2003, ISBN 9283224124</ref> recommends the following pathological types:
===Invasive Breast Carcinomas===
* [[Ductal carcinoma|Invasive ductal carcinoma]]
** Most are "not otherwise specified"
** The remainder are given subtypes:
*** Mixed type carcinoma
*** Pleomorphic carcinoma
*** Carcinoma with osteoclastic giant cells
*** Carcinoma with choriocarcinomatous features
*** Carcinoma with melanotic features
* Invasive lobular carcinoma
* Tubular carcinoma
* Invasive cribriform carcinoma
* [[Medullary carcinoma]]
* Mucinous carcinoma and other tumours with abundant mucin
** Mucinous carcinoma
** Cystadenocarcinoma and columnar cell mucinous carcinoma
** [[Signet ring cell carcinoma]]
* [[Neuroendocrine]] tumours
** Solid neuroendocrine carcinoma ([[carcinoid]] of the breast)
** Atypical carcinoid tumour
** Small cell / [[oat cell carcinoma]]
** Large cell neuroendocrine carcioma
* Invasive papillary carcinoma
* Invasive micropapillary carcinoma
* Apocrine carcinoma
* Metaplastic carcinomas
** Pure epithelial metaplastic carciomas
*** [[Squamous cell carcinoma]]
*** Adenocarcinoma with spindle cell metaplasia
*** Adenosquamous carcinoma
*** [[Mucoepidermoid carcinoma]]
** Mixed epithelial/mesenchymal metaplastic carcinomas
* Lipid-rich carcinoma
* Secretory carcinoma
* Oncocytic carcinoma
* Adenoid cystic carcinoma
* Acinic cell carcinoma
* Glycogen-rich clear cell carcinoma
* Sebaceous carcinoma
* [[Inflammatory breast cancer|Inflammatory carcinoma]]
* Bilateral breast carcinoma
===Mesenchymal Tumors (Including [[Sarcoma]])===
* Haemangioma
* Angiomatosis
* Haemangiopericytoma
* Pseudoangiomatous stromal hyperplasia
* Myofibroblastoma
* Fibromatosis (aggressive)
* Inflammatory myofibroblastic tumour
* [[Lipoma]]
** Angiolipoma
* Granular cell tumour
* [[Neurofibroma]]
* [[Schwannoma]]
* Angiosarcoma
* Liposarcoma
* Rhabdomyosarcoma
* Osteosarcoma
* [[Leiomyoma]]
* Leiomysarcoma
===Precursor Lesions===
* Lobular neoplasia
** lobular carcinoma in situ
* Intraductal proliferative lesions
** Usual ductal [[hyperplasia]]
** Flat epithelial hyperplasia
** Atypical ductal hyperplasia
** [[Ductal carcinoma in situ]]
* Microinvasive carcinoma
* Intraductal papillary neoplasms
** Central [[papilloma]]
** Peripheral papilloma
** Atypical papilloma
** Intraductal papillary carcinoma
** Intracystic papillary carcinoma
===Benign Epithelial Lesions===
* Adenosis, including variants
** Sclerosing adenosis
** Apocrine adenosis
** Blunt duct adenosis
** Microglandular adenosis
** Adenomyoepithelial adenosis
* Radial scar / complex sclerosing lesion
* Adenomas
** Tubular adenoma
** Lactating adenoma
** Apocrine adenoma
** [[Pleomorphic adenoma]]
** Ductal adenoma
===Myoepithelial Lesions===
* Myoepitheliosis
* Adenomyoepithelial adenosis
* Adenomyoepithelioma
* Malignant myoepithelioma
===Fibroepithelial Tumors===
* [[Fibroadenoma]]
* [[Phyllodes tumour]]
** Benign
** Borderline
** Malignant
* Periductal stromal sarcoma, low grade
* Mammary [[hamartoma]]
===Tumours of the Nipple===
* Nipple adenoma
* Syringomatous adenoma
* [[Paget's disease]] of the nipple
===Malignant [[Lymphoma]]===
===Metastatic Tumors===
===Tumors of the Male Breast===
* [[Gynecomastia]]
* Carcinoma
** In situ
** Invasive
==Histologic Types==
The classifications above show that breast cancer is usually, but not always, classified by its histological appearance. Rare variants are defined on the basis of [[physical exam]] findings. For example, [[Inflammatory breast cancer]] (IBC), a form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other [[carcinoma]]s by the [[inflammation|inflamed]] appearance of the affected breast.<ref>{{cite journal |author=Giordano SH, Hortobagyi GN |title=Inflammatory breast cancer: clinical progress and the main problems that must be addressed |journal=Breast Cancer Res. |volume=5 |issue=6 |pages=284-8 |year=2003 |pmid=14580242 |doi=10.1186/bcr608}} [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14580242 Free Full Text].</ref> In the future, some pathologic classifications may be changed. For example, a subset of ductal carcinomas may be re-named [[basal-like carcinoma]] (part of the [[Triple Negative Breast Cancer|"triple-negative" tumors]]).
===Carcinomas===
====In situ====
*[[Ductal carcinoma]] (DCIS) 80%
*Lobular carcinoma (LCIS) 20%
====Invasive====
*Carcinoma NOS (not otherwise specified)
*Lobular carcinoma
*Tubular/cribriform carcinoma
*Mucinous (colloid) carcinoma
*Medullary carcinoma
*Papillary carcinoma
*Metaplastic carcinoma
====Sarcomas====
*[[Phyllodes tumour]]
===Clinical categorizations===
Breast cancer is occasionally classified clinically (on [[physical exam]] findings, [[medical history|(medical) history]]). [[Inflammatory breast cancer]] (IBC) is an example of a clinically classified breast cancer and can be any histologic type.<ref>{{cite journal |author=Giordano SH, Hortobagyi GN |title=Inflammatory breast cancer: clinical progress and the main problems that must be addressed |journal=Breast Cancer Res. |volume=5 |issue=6 |pages=284-8 |year=2003 |pmid=14580242 |doi=10.1186/bcr608}} [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14580242 Free Full Text].</ref>


==Gallery==
==Gallery==

Revision as of 00:33, 17 January 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Assistant Editor(s)-In-Chief: Jack Khouri, Mirdula Sharma, MBBS [2]

Overview

Classification Based on Histopathology

Malignant Tumors

Type Subtype

Adenocarcinoma[1]

Ductal

  • Ductal carcinoma in situ (DCIS)
  • comedo type: ~60% of DCIS
  • non comedo type: ~40% of DCIS
  • papillary
  • micropapillary
  • cribriform
  • solid
  • intracystic papillary carcinoma in situ
  • invasive ductal carcinoma
  • invasive ductal carcinoma not otherwise specified (NOS): ~65%
  • tubular carcinoma of breast: ~7-8%
  • tubulolobular carcinoma of breast
  • medullary carcinoma of breast (MCB): ~2%
  • mucinous (colloid) carcinoma: ~2%
  • malignant papillary lesions of the breast
  • papillary carcinoma of breast: 1-2% 1

Lobular

  • lobular carcinoma in situ (LCIS)
  • invasive lobular carcinoma: ~10%

Other malignant breast tumors

  • inflammatory carcinoma of breast: 1-4%
  • Paget disease of the nipple
  • triple negative and basal-like breast cancers
  • metaplastic carcinoma of the breast
  • adenoid cystic carcinoma of the breast: <0.4%
  • apocrine carcinoma of the breast

Sarcoma

  • angiosarcoma of the breast
  • fibrosarcoma of breast
  • extra-skeletal osteosarcoma of breast
  • malignant phyllodes tumor
  • angiosarcoma
  • rhabdomyosarcoma

Lymphoma

  • Non-hodgkin lymphoma

Metastases to the breast

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

Benign Tumors

  • Phyllodes tumor[2]
  • mammary fibromatosis: 0.2% of all breast tumours 5
  • benign papillary lesions of the breast
  • papilloma
  • 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 tumour of the breast

Staging

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.[3]

Stage 0

There are 3 types of breast carcinoma in situ:

  • Ductal carcinoma in situ (DCIS) is a noninvasive condition in which abnormal cells are found in the lining of a breast duct. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, DCIS may become invasive cancer and spread to other tissues. At this time, there is no way to know which lesions could become invasive.
  • Lobular carcinoma in situ (LCIS) is a condition in which abnormal cells are found in the lobules of the breast. This condition seldom becomes invasive cancer.
  • Paget disease of the nipple is a condition in which abnormal cells are found in the nipple only.

Stage 1

In stage I, cancer has formed. Stage I is divided into stages IA and IB.

  • In stage IA, the tumor is 2 centimeters or smaller. Cancer has not spread outside the breast.
  • In stage IB, small clusters of breast cancer cells (larger than 0.2 millimeter but not larger than 2 millimeters) are found in the lymph nodes and either:
  • no tumor is found in the breast; or
  • the tumor is 2 centimeters or smaller.

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 - 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(DCIS) - Intraductal Carcinoma in situ
    • Tis(LCIS) - Lobular Carcinoma in situ
    • Tis(Paget's) - 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:

Lymph Node - 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

Metastases - 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).

Gallery

References

  1. Breast Neoplasm. Radiopedia. (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on January 16, 2016
  2. Breast Neoplasms. Radiopaedia (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on january 16, 2016
  3. Breast Cancer. National Cancer Institute (2016) http://www.cancer.gov/types/breast/patient/breast-treatment-pdq#link/_148 Accessed on January 16, 2016


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