Breast cancer is categorized variously by histological type, receptor type and molecular phenotype.
Histological breast cancer types
Invasive breast cancer
Histology refers to the microscopic structure of tissues. Invasive, or infiltrating, breast carcinoma is characterized by cancer cells that have invaded healthy surrounding tissue. Invasive breast carcinoma is divided into five main histological types:
- Ductal carcinoma — develops in the milk ducts of the breasts — up to 75% of cases
- Lobular carcinoma — forms in the cells that line the milk-producing glands (lobules) — up to 15% of cases
- Mucinous carcinoma — tumor cells are poorly defined and produce mucus — up to 2% of cases
- Adenoid cystic carcinoma — tumor cells resemble adenoid (glandular) and cystic cells — extremely rare
- Mixed tumors — tumor cells are of different types in one tumor, e.g., ductal and lobular — rare.
- Medullary carcinoma — starts in the milk ducts, but tumor cells resemble the medulla (gray matter) of the brain — up to 15% of all breast cancer cases
- Inflammatory breast cancer — starts in the milk ducts, but is characterized by involvement of the skin — up to 3% of cases
- Tubular carcinoma — tumor cells have a tubular structure when viewed under the microscope — up to 2% of cases
- Piaget's disease of the nipple — characterized by nipple involvement — less than 1% of cases
- Metaplastic carcinoma — starts in the milk ducts, but tumor contains non-breast cells (e.g., skin, bone) — extremely rare.
While most breast cancers are carcinomas, there are two types of breast sarcomas, which form in connective tissue:
- Angiosarcoma — forms in cells that line the blood vessels in the breast or underarm area — extremely rare
- Phyllodes tumor — forms in the connective tissue of the breast. Tumor has a leaf-shaped pattern of growth — extremely rare. May be benign, malignant or borderline (in between noncancerous and cancerous).
Noninvasive breast cancer
Noninvasive breast cancer, which has not infiltrated healthy surrounding tissue and is not considered capable of spreading to other parts of the body, is divided into two main histological types:
- Ductal carcinoma in situ (DCIS) — ductal cancer cells form but remain inside the milk ducts of the breasts
- Lobular carcinoma in situ (LCIS), also known as lobular neoplasia — abnormal cells fill milk-producing glands (lobules).
Most male breast cancer cases (up to 90%) are hormone receptor-positive ductal carcinomas. The remainder are mostly DCIS.
Breast cancer is also classified by cancer cell receptor status. Receptors are proteins found on some cells to which hormones such as estrogen and other compounds will attach. For example, estrogen receptor positive (ER+) cancer cells contain the estrogen-receptor protein. Breast cancer cells are categorized according to the following main types of receptors:
- Estrogen receptor — can be positive (ER+) or negative (ER-)
- Progesterone receptor — can be positive (PR+) or negative (PR-)
- HER2/neu — can be HER2/neu overexpressing (sometimes referred to as HER2 positive) or not.
Estrogen receptors have been further categorized into two types: estrogen receptor-alpha and estrogen receptor-beta (ERα and ERβ). Some compounds that bind to ERα do not bind to estrogen ERβ and vice versa.
There are many other types of receptors that influence breast cancer and normally will not be included in routine breast cancer pathology but whose actions may be evaluated in breast cancer studies. Examples are vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), and androgen receptor (AR — AR+ disease is known as apocrine carcinoma).
Molecular phenotypes: luminal, HER2 and basal breast cancer types
Mammary glands are comprised primarily of basal cells and luminal cells. Luminal cells are designed to secrete water and nutriments to produce breast milk whereas basal cells help funnel the milk through the ductal branches (by means of contraction). Researchers are increasingly categorizing breast cancer according to whether it is luminal, basal (also known as basal-like) or HER2 positive. These are molecular phenotypes, as determined by gene expression profiling. Based on comprehensive gene expression, breast cancer can be divided into luminal (expressing luminal cytokeratins 8 and 18), basal (characterized by cytokeratins 5 and 17), and HER positive (mostly, but not all, HER2 amplified). Luminal tumors can further be subdivided into luminal A and luminal B. It is hoped that these new classifications will help tailor breast cancer treatment, for example by identifying those most likely to benefit from a given type of chemotherapy.
In practice, these breast cancer types often are defined using the receptor subtype markers above, grouped in ways considered to be reasonable approximations of the molecular phenotypes. As such, there is not complete agreement concerning characteristics of these types. Below are the most common descriptions we have come across:
- Luminal A - strong estrogen receptor positive (ER+) and progesterone receptor positive (PR+) and not HER2 overexpressing, with low tumor grade and low proliferation (Ki-67 < 15%). ER+/PR+/HER2- tumors are luminal A. The luminal A subtype represents up to 60% of all breast cancer patients.
- Luminal B - weak to moderate ER+/PR+. Can be HER2- or HER2+. May have low tumor grade, but with higher proliferation and DNA instability than luminal A. ER+/PR- and ER-/PR+ tumors are normally luminal B
- HER2+ - HER2/neu overexpressing
- Basal or basal-like - most often triple negative, i.e., ER-/PR-/HER2-. However, not all basal tumors are triple negative and not all triple negative tumors are basal.