Breast cancer classification divides breast cancer into categories according to different schemes criteria and serving a different purpose. The major categories are the histopathological type, the grade of the tumor, the stage of the tumor, and the expression of proteins and genes. As knowledge of cancer cell biology develops these classifications are updated.
The purpose of classification is to select the best treatment. The effectiveness of a specific treatment is demonstrated for a specific breast cancer (usually by randomized, controlled trials). That treatment may not be effective in a different breast cancer. Some breast cancers are aggressive and life-threatening, and must be treated with aggressive treatments that have major adverse effects. Other breast cancers are less aggressive and can be treated with less aggressive treatments, such as lumpectomy.
Treatment algorithms rely on breast cancer classification to define specific subgroups that are each treated according to the best evidence available. Classification aspects must be carefully tested and validated, such that confounding effects are minimized, making them either true prognostic factors, which estimate disease outcomes such as disease-free or overall survival in the absence of therapy, or true predictive factors, which estimate the likelihood of response or lack of response to a specific treatment.
Classification of breast cancer is usually, but not always, primarily based on the histological appearance of tissue in the tumor. A variant from this approach, defined on the basis of physical exam findings, is that 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, which correlates with increased cancer aggressivity.
Schemes or aspects
Overview Breast cancers can be classified by different schemata. Each of these aspects influences treatment response and prognosis. Description of a breast cancer would optimally include all of these classification aspects, as well as other findings, such as signs found on physical exam. A full classification includes histopathological type, grade, stage (TNM), receptor status, and the presence or absence of genes as determined by DNA testing: Histopathology. Although breast cancer has many different histologies, the considerable majority of breast cancers are derived from the epithelium lining the ducts or lobules, and are classified as mammary ductal carcinoma. Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding tissue. In contrast, invasive carcinoma invades the surrounding tissue.Merck Manual, Professional Edition , Ch. 253, Breast Cancer. Perineural and/or lymphovascular space invasion is usually considered as part of the histological description of a breast cancer, and when present may be associated with more aggressive disease. Grade. Grading focuses on the appearance of the breast cancer cells compared to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation. In cancer, the cells that would normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low-grade), moderately differentiated (intermediate-grade), and poorly differentiated (high-grade) as the cells progressively lose the features seen in normal breast cells. Poorly differentiated cancers have a worse prognosis. Stage. The TNM classification for staging breast cancer is based on the size of the cancer where it originally started in the body and the locations to which it has travelled. These cancer characteristics are described as the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, neck, and inside the chest, and whether the tumor has metastasized (M) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis. The main stages are: Stage 0 which is in situ disease or Paget's disease of the nipple. Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS). Stages 1–3 are within the breast or regional lymph nodes. Stage 4 is a metastatic cancer. Metastatic breast cancer has a less favorable prognosis. Receptor status. Cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to receptors, and this causes changes in the cell. Breast cancer cells may have various receptors, the three most important in the present classification being estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. The presence or absence of a receptor is denoted as positive (+) or negative (−), respectively. Cells with none of these receptors are called basal-like or triple negative. HER2-low has some HER2 proteins on the cell surface, but not enough to be classified as HER2-positive. Trastuzumab deruxtecan is the first approved therapy by the US Food and Drug Administration (FDA) targeted to people with the HER2-low breast cancer subtype. DNA-based classification. Understanding the specific details of a particular breast cancer may include looking at the cancer cell DNA or RNA by several different laboratory approaches. When specific DNA mutations or gene expression profiles are identified in the cancer cells this may guide the selection of treatments, either by targeting these changes, or by predicting from these alterations which non-targeted therapies are most effective. Other classification approaches. Computer models such as Adjuvant can combine the various classification aspects according to validated algorithms and present visually appealing graphics that assist in treatment decisions. The USC/Van Nuys prognostic index (VNPI) classifies ductal carcinoma in situ (DCIS) into dissimilar risk categories that may be treated accordingly. The choice of which treatment to receive can be substantially influenced by comorbidity assessments. Familial breast cancers may potentially undergo dissimilar treatment (such as mastectomy).
Histopathology
Histopathologic classification is based upon characteristics seen upon light microscopy of biopsy specimens. They can broadly be classified into: Carcinoma in situ. This group constitutes about 15-30% of breast biopsies, more so in countries with high coverage of breast screening programs.Page 1084 in: These have favorable prognosis, with 5-year survival rates of 97-99%.Ductal carcinoma in situ: 99% - Lobular carcinoma in situ: 97% - Invasive carcinoma. This group constitutes the other 70-85%. The most common type in this group is invasive ductal carcinoma, representing about 80% of invasive carcinomas. In the US, 55% of breast cancers are invasive ductal carcinoma.Percentage values are from United States statistics 2004. Subtype specific incidences are taken from Table 6 (invasive) and Table 3 (in situ) from . These are divided by total breast cancer incidence (211,300 invasive and 55,700 in situ cases) as reported from Breast Cancer Facts & Figures 2003–2004 Invasive lobular carcinoma represent about 10% of invasive carcinomas, and 5% of all breast cancers in the US. The overall 5-year survival rate for both invasive ductal carcinoma and invasive lobular carcinoma was approximately 85% in 2003.NOTE: Number really refers to invasive ductal carcinoma, despite title. Ductal carcinoma in situ, on the other hand, is in itself harmless, although if untreated approximately 60% of these low-grade DCIS lesions will become invasive over the course of 40 years in follow-up.
WHO classification The 2012 World Health Organization (WHO) classification of tumors of the breast which includes benign (generally harmless) tumors and malignant (cancerous) tumors, recommends the following pathological types:
Invasive breast carcinomas Invasive carcinoma Most are "not otherwise specified" The remainder are given subtypes: Pleomorphic carcinoma Carcinoma with osteoclast giant cells Carcinoma with choriocarcinoma features Carcinoma with melanotic features Invasive lobular carcinoma Classic Solid Mixed Alveolar Tubulolobular Pleomorphic Tubular carcinoma Invasive cribriform carcinoma of the breast (also termed invasive cribriform carcinoma) Medullary carcinoma of the breast Mucinous carcinoma and other tumours with abundant mucin Mucinous carcinoma of the breast Cystadenocarcinoma and columnar cell mucinous carcinoma Signet ring cell carcinoma Neuroendocrine tumours Solid neuroendocrine carcinoma (carcinoid of the breast) Atypical carcinoid tumor Small cell / oat cell carcinoma Large cell neuroendocrine carcinoma Invasive papillary carcinoma Invasive micropapillary carcinoma Pure apocrine carcinoma of the breast Apocrine-like invasive carcinoma Metaplastic carcinomas Pure epithelial metaplastic carcinomas Squamous cell carcinoma Adenocarcinoma with spindle cell metaplasia Adenosquamous carcinoma Mucoepidermoid carcinoma Mixed epithelial/mesenchymal metaplastic carcinomas (Other well-accepted subtypes of metaplastic mammary carcinoma thought to have clinical significance but not included in the decade old WHO classification: Matrix-producing carcinoma Spindle cell carcinoma Carcinosarcoma Squamous cell carcinoma of mammary origin Metaplastic carcinoma with osteoclastic giant cells) 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) Hemangioma Angiomatosis Hemangiopericytoma Pseudoangiomatous stromal hyperplasia Myofibroblastoma Fibromatosis (aggressive) Inflammatory myofibroblastic tumor Lipoma Angiolipoma Granular cell tumour Neurofibroma Schwannoma Angiosarcoma Liposarcoma Rhabdomyosarcoma Osteosarcoma Leiomyoma Leiomyosarcoma
Tumors of the male breast Gynecomastia (benign) Carcinoma (See Male breast cancer section on types of breast cancer) In situ Invasive
Malignant lymphoma Non-Hodgkin lymphoma
Metastatic tumors to the breast from other places in the body
Precursor lesions Lobular neoplasia lobular carcinoma in situ Intraductal proliferative lesions Usual ductal hyperplasia Flat epithelial hyperplasia Atypical ductal hyperplasia Ductal carcinoma in situ Apocrine 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 tumours Fibroadenoma Phyllodes tumour Benign Borderline Malignant Periductal stromal sarcoma, low-grade Mammary hamartoma
Benign tumors of the nipple Nipple adenoma Syringomatous adenoma Paget's disease of the nipple Malignant tumors of the nipple Malignant Paget's disease of the nipple
Grade