Breast cancer classification

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

Overview

Breast cancer may be classified according to [classification method] into [number] subtypes/group.

Classification Based on Histopathology

Malignant Tumors

Type Subtype

Ductal

  • Comedo type: ~60%
  • Non-comedo type: ~40%
  • 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: ~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 don’t 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’t 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:
  • Low grade,
  • Grows slowly,
  • Have the best prognosis
  • Luminal B:
  • Grows faster
  • Have bad prognosis

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.[2]

Stage 0

There are 3 types of breast carcinoma in situ:

  • Noninvasive condition in which abnormal cells are found in the lining of a breast duct
  • Abnormal cells have not spread outside the duct to other tissues in the breast
  • May become invasive cancer and spread to other tissues
  • Abnormal cells are found in the lobules of the breast
  • This condition seldomly becomes invasive
  • 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 - 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).

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.[3]

  • 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

References

  1. 1.0 1.1 Breast Neoplasm. Radiopedia. (2015) http://radiopaedia.org/articles/breast-neoplasms Accessed on January 16, 2016
  2. Breast Cancer. National Cancer Institute (2016) http://www.cancer.gov/types/breast/patient/breast-treatment-pdq#link/_148 Accessed on January 16, 2016
  3. 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


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Grade Combined score Description

I

3-5

Low-grade (well-differentiated) tumors that do not appear to be growing quickly and are less likely to spread

II

6-7

Intermediate-grade (moderately differentiated) tumors that have features between grade 1 and 3

III

8-9

High-grade (poorly differentiated) tumors that tend to grow faster and are more likely to spread