Breast cancer types

Breast cancer is categorized variously by histological type, receptor type and molecular phenotype. Histology refers to the microscopic structure of tissues. Receptors are proteins found on some cells to which hormones such as estrogen can attach. Molecular phenotypes have been determined by gene expression profiling.

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 has some less common subtypes:

• 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:

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:

Both DCIS and LCIS increase the possibility of invasive breast cancer, although DCIS is more likely to lead to it. The subsequent invasive breast cancer may be of a different type. For example, a woman with LCIS may go on to develop ductal breast cancer. Papillary carcinoma is a type of DCIS that rarely becomes invasive.

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:

Generally speaking, each of the main histological types can have any combination of receptor status. For example, lobular breast cancer can have ER-/PR- status, although lobular is more likely to be ER+/PR+ (also known as hormone receptor positive). Triple negative refers to breast cancer that is estrogen receptor negative (ER-), progesterone receptor negative (PR-), and does not overexpress HER2 (human epidermal growth factor receptor 2). There are four possible combinations of estrogen and progesterone receptor status: ER+/PR+, ER+/PR-, ER-/PR+ and ER-/PR-.

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) (apocrine carcinoma is AR+).

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 HER2 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:

Two additional types, claudin-low and normal-like, have also been described, but these categories appear to be used primarily in studies focusing on phenotype and are not in general use.