Breast cancer classification

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

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 carcinomas by the inflamed appearance of the affected breast.[1] 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" tumors).

Major Schemes

  • Pathology - A pathologist will categorize each tumor based on its 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 ducts; and invasive lobular carcinoma, malignant cancer in the breast's lobules.
  • 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 & 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 oncologist choose the most appropriate treatment. More genes and/or proteins may be tested in the future (eg PAX2[2]).
  • Stage of a tumor - The currently accepted staging scheme for breast cancer is the TNM classification.


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.

Staging

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).

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[3] recommends the following pathological types:

Invasive Breast Carcinomas

  • 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
  • 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
  • Lipid-rich carcinoma
  • Secretory carcinoma
  • Oncocytic carcinoma
  • Adenoid cystic carcinoma
  • Acinic cell carcinoma
  • Glycogen-rich clear cell carcinoma
  • Sebaceous carcinoma
  • 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
  • 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

Myoepithelial Lesions

  • Myoepitheliosis
  • Adenomyoepithelial adenosis
  • Adenomyoepithelioma
  • Malignant myoepithelioma

Fibroepithelial Tumors

Tumours of the Nipple

Malignant Lymphoma

Metastatic Tumors

Tumors of the Male Breast

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 carcinomas by the inflamed appearance of the affected breast.[4] 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" tumors).

Carcinomas

In situ

Invasive

  • Carcinoma NOS (not otherwise specified)
  • Lobular carcinoma
  • Tubular/cribriform carcinoma
  • Mucinous (colloid) carcinoma
  • Medullary carcinoma
  • Papillary carcinoma
  • Metaplastic carcinoma

Sarcomas

Clinical categorizations

Breast cancer is occasionally classified clinically (on physical exam findings, (medical) history). Inflammatory breast cancer (IBC) is an example of a clinically classified breast cancer and can be any histologic type.[5]

Gallery

  • Infiltrating ductal carcinoma of the Breast assayed with anti Mucin 1 antibody

    Infiltrating ductal carcinoma of the Breast assayed with anti Mucin 1 antibody

  • Breast cancer (Infiltrating ductal carcinoma of the breast) assayed with anti HER-2 (ErbB2) antibody

    Breast cancer (Infiltrating ductal carcinoma of the breast) assayed with anti HER-2 (ErbB2) antibody

  • Invasive lobular carcinoma of the breast demonstrating a predominantly lobular growth pattern

    Invasive lobular carcinoma of the breast demonstrating a predominantly lobular growth pattern

  • Metaplastic (sarcomatoid) carcinoma of the breast.

    Metaplastic (sarcomatoid) carcinoma of the breast.

  • Histopathologic image from ductal cell carcinoma in situ (DCIS) of breast. Hematoxylin-eosin stain.

    Histopathologic image from ductal cell carcinoma in situ (DCIS) of breast. Hematoxylin-eosin stain.

  • Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. Hematoxylin and eosin stain.

    Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. Hematoxylin and eosin stain.

  • Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. HER-2/neu oncoprotein expression by Ventana immunostaining system.

    Histopathology of invasive ductal carcinoma of the breast representing a scirrhous growth. Core needle biopsy. HER-2/neu oncoprotein expression by Ventana immunostaining system.

  • Breast cancer (Infiltrating ductal carcinoma of the breast) dyed with H&E

    Breast cancer (Infiltrating ductal carcinoma of the breast) dyed with H&E

  • Histopathology of intraductal papilloma of the breast by excisional biopsy. Hematoxylin and eosin stain.

    Histopathology of intraductal papilloma of the breast by excisional biopsy. Hematoxylin and eosin stain.

  • Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for alpha-smooth muscle actin.

    Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for alpha-smooth muscle actin.

  • Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for p63 protein.

    Histopathology of intraductal papilloma of the breast by excisional biopsy. Immunostaining for p63 protein.

  • Breast fibroadenoma

    Breast fibroadenoma

  • Breast fibroadenoma

    Breast fibroadenoma

  • Histopathologic image of breast fibroadenoma. Core needle biopsy. Hematoxylin & eosin stain.

    Histopathologic image of breast fibroadenoma. Core needle biopsy. Hematoxylin & eosin stain.

  • Histopathologic image of breast fibroadenoma. Core needle biopsy. Hematoxylin & eosin stain.

    Histopathologic image of breast fibroadenoma. Core needle biopsy. Hematoxylin & eosin stain.

References

  1. ↑ Giordano SH, Hortobagyi GN (2003). "Inflammatory breast cancer: clinical progress and the main problems that must be addressed". Breast Cancer Res. 5 (6): 284–8. doi:10.1186/bcr608. PMID 14580242. Free Full Text.
  2. ↑ http://cordis.europa.eu/fetch?CALLER=EN_NEWS&ACTION=D&SESSION=&RCN=30093
  3. ↑ Tumours of the breast and female genital organs, WHO classification of tumours, 2003, ISBN 9283224124
  4. ↑ Giordano SH, Hortobagyi GN (2003). "Inflammatory breast cancer: clinical progress and the main problems that must be addressed". Breast Cancer Res. 5 (6): 284–8. doi:10.1186/bcr608. PMID 14580242. Free Full Text.
  5. ↑ Giordano SH, Hortobagyi GN (2003). "Inflammatory breast cancer: clinical progress and the main problems that must be addressed". Breast Cancer Res. 5 (6): 284–8. doi:10.1186/bcr608. PMID 14580242. Free Full Text.


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