Breast cancer subtypes

Cell types

Breasts are made up of two main types of cells; the breast lobules, which make milk, and the breast ducts which carry the milk to the nipple.

• Ductal carcinoma is cancer that starts in the ducts. This is the most common type of breast cancer.
• Lobular carcinoma starts in the breast lobules. This is less common than ductal carcinoma.  

There are other, very rare types of breast cancer. Inflammatory breast cancer is a very fast growing type of ductal carcinoma. Paget's disease of the breast is a type of ductal carcinoma that affects the nipple and areola. Phyllodes tumors start in the connective tissue of the breast. 

Stages

The stage of a cancer refers to whether the cancer has spread beyond the breast, and if so, where in the body the cancer has spread. Measuring the stage of breast cancer helps doctors decide how to treat it. Breast cancer most often starts as a lump within the breast that can grow and spread: 

• within the breast
• to nearby tissue (such as lymph nodes, skin or the chest wall)
• through the blood stream or lymph system to distant organs (metastasis) 

In breast cancer, there are five major stages.  

• Stage 0: A stage 0 breast cancer is known as a ductal carcinoma in situ (DCIS), a non-invasive form of the disease. The tumor cells are contained within the ducts of the breasts, and have not invaded beyond the duct. Cancers caught and treated at stage 0 are very unlikely to recur or spread.
• Stage 1: A small tumor (< 2 cm) that is contained within the breast and has not spread to the lymph nodes.
• Stage 2: A stage 2 breast cancer can be either a larger tumor that involves the breast only, or a tumor that has spread to some lymph nodes in the armpit.
• Stage 3: A stage 3 breast cancer can be either a tumor in the breast that invades the skin or chest muscle, or a tumor that involve several lymph nodes surrounding the breast (in the armpit, near the collarbone, near the breast bone). Stage 3 breast cancers are sometimes called “locally advanced.”
• Stage 4 or metastatic: A stage 4 breast cancer is one that has spread beyond the breast and the regional lymph nodes to another place in the body, such as the bone, lung, and/or liver. Stage IV breast cancers are also called “advanced” or “metastatic.”

Breast cancers diagnosed at stages 0-3 are considered curable, so treatment plans are made with the goal of cure. Metastatic breast cancer is often treatable at diagnosis. Over time, metastatic breast cancer is likely to progress or recur; sometimes after several different types of treatment. There are many different treatments available for metastatic breast cancer, and clinical trials testing new treatments are often available. 

Subtypes and biomarkers 

After a biopsy or surgery confirms breast cancer, pathologists look closely at the cells for additional clues on how to best treat the cancer. All breast cancers are tested for common changes, called tumor biomarkers: estrogen receptor (ER), progesterone receptor (PR), and HER2. The results of these tumor biomarker tests play a major role in choice of cancer treatment:

Hormone receptor (HR or ER/PR) testing

• Doctors use hormone receptor tests to measure if cancers are "hormone sensitive" and might respond to hormone therapy. Doctors may refer to these tests as hormone receptor tests (HR tests) or estrogen and progesterone receptor tests (ER/PR tests). In general, they refer to the same test. 
  • HR-positive or ER/PR-positive: breast cancers with these biomarkers are called "hormone sensitive" breast cancers. These are usually treated with hormone therapy. Hormone therapy may be combined with chemotherapy or targeted therapy depending on the stage of the tumor and other factors. 
  • HR-negative or ER/PR-negative: these are almost always treated with chemotherapy and, or targeted therapy, because hormone therapy does not work well for these types of tumors.

HER2 testing

• Doctors use a test to measure the amount of a protein called HER2 on the surface of cancer cells. Cancers with a large amount of HER2 protein are called HER2-positive. These cancers often respond to certain types of targeted therapies.
• HER2 test results range from 0 to 3+.
  • HER2-positive: A tumor with a HER2 score of 3+ is considered HER2-positive. These cancers are often treated with a type of targeted therapy known as "anti-HER2 therapy." Common anti-HER2 therapies include Herceptin (trastuzumab) and Perjeta (pertuzumab). Anti-HER2 therapy may be given with chemotherapy for people with early-stage, curable tumors. People whose tumors are HER2-positive and ER-positive receive hormone therapy, as well as chemotherapy and anti-HER2 therapy.
  • HER2-low: In the past, a tumor with a score of 0 to 1+ was called HER2-negative and a score of 2+ was considered borderline. Updated scoring labels tumors with 1+ and 2+ as "HER2-low." Some people with advance or metastatic breast cancer that is HER2-low may benefit from an anti-HER2 therapy known as Enhertu (trastuzumab deruxtecan). 
  • HER2-negative: A tumor with a HER2 score of 0 is considered HER2-negative.  

possible HER2 results

Triple-negative breast cancer

• Triple-negative breast cancers: tumors that are negative for all three markers (ER, PR and HER2) are referred to as triple-negative breast cancer or TNBC for short. Triple-negative breast cancers are almost always treated with chemotherapy.

Additional biomarker tests can be performed on tumor samples or blood to help guide treatment.

• For people with early-stage (stage 1 or 2) cancer, prognostic tests can help guide decisions about chemotherapy and hormone therapy. These tests include Oncotype DX, MammaPrint, and Prosigna.
• For people with advanced cancers, tumor testing can look for additional biomarkers to help guide the choice of targeted therapies.