Breast cancer(s) are classified by several grading systems. Each of these influences the prognosis and can affect treatment response. Description of a breast cancer optimally includes all of these factors:
Breast cancer is usually classified primarily by its histological appearance. Most cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as ductal or lobular carcinomas. Carcinoma in situ is growth of low grade cancerous or pre-cancerous cells within a particular tissue compartment (such as the mammary duct – without invasion of the surrounding tissue. In contrast, invasive carcinoma does not confine itself to the initial tissue compartment.
Grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue. Normal cells in an organ such as the breast become differentiated, meaning that they take on specific shapes and forms which reflect their function as part of that organ. Cancerous cells lose that differentiation. In cells affected by breast cancer, the cells that would normally line up in an orderly fashion to make the milk ducts become disorganized and the cell division becomes uncontrolled. In addition, cell nuclei become less uniform. In describing how the cells have been affected, pathologist use the following: 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 generally have a worse prognosis.
Breast cancer staging utilize the TNM system which is based on the size of the tumor (T ), whether or not the tumor has spread to the lymph nodes (N ) in the armpits, and whether the tumor has metastasized (M ) (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 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 that has a less favorable prognosis.
Breast cancers cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers – such as hormones – bind to these receptors and this causes changes in the cell. Breast cancer cells may or may not have three (3) important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2/neu.
The ER cancer cells are dependent on estrogen for their growth, so they can be treated with drugs that block the estrogen’s effects and generally have a better prognosis. Comparatively, HER2-type breast cancer has a worse prognosis, but the cancer cells respond to drugs such as monoclonal antibody trastuzumab (trade name Herceptin ) combined with conventional chemotherapy which result in a significantly improved prognosis. Cells that contain none of these receptors are called basal-like or triple negative.
Deoxyribonucleic (DNA) assays
DNA testing of various types including DNA micro-arrays have compared normal cells to breast cancer cells. The specific changes in a particular breast cancer can be used to classify the cancer in several ways and may assist in choosing the most effective treatment for that specific DNA type.
How is breast cancer treated?
The usual course of treatment is surgery possibly followed by chemotherapy, radiation, or a combination of both because a multi-discipline approach is preferable. Hormone positive cancers are treated with long term hormone blocking therapy. Treatment(s) are given with increasing aggressiveness according to the prognosis and risk of recurrence.
Stage 1 cancers
(Including DCIS) have an excellent prognosis and are generally treated with lumpectomy (see below) and sometimes radiation. HER2 cancers should be treated with the trastuzumab (Herceptin) regime. The use of chemotherapy is uncommon for other types of Stage 1 cancers.
Stage 2 & 3 cancers
These cancers have a progressively poorer prognosis and a greater risk of recurrence and are generally treated with surgery (lumpectomy or mastectomy either with or without lymph node removal). Additional treatment(s) include: chemotherapy, (plus Herceptin for HER2 cancers) and, in some cases, radiation (particularly following large cancers, multiple positive nodes, or lumpectomy).
Stage 4 cancers
Metastatic cancer has a poor prognosis and is managed by various combination of treatments including surgery, radiation, chemotherapy, and targeted therapies. The ten (10) year survival rate is five percent (5%) without treatment and ten percent (10%) with optimal treatment.
Surgery involves the physical removal of the tumor, typically along with some of the surrounding apparently healthy tissue. Standard surgeries include:
Mastectomy – removal of the entire breast
Quadrantectomy – removal of one-quarter of the breast
Lumpectomy – removal of a small part of the breast
If the patient desires, breast reconstruction surgery, may be performed to create an aesthetic appearance. Patients can also opt to use a prostheses to simulate a breast, or choose a flat chest.
Drugs used either after and/or in addition to surgery are called adjuvant therapy . The use of chemotherapy prior to surgery is referred to as neo-adjuvant therapy . There are currently three (3) main groups of medications used for adjuvant breast cancer treatment: hormone-blocking therapy, chemotherapy, and monoclonal antibodies. It should be noted, however, that not all of these are appropriate for every person with breast cancer.
Hormone blocking therapy
Some forms of breast cancer require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER) and progesterone receptors (PR) on their surface (sometimes referred to together as hormone receptors). These ER cancers can be treated with drugs that either block the receptors or, alternatively, blocking the production of estrogen with an aromatase inhibitor. The latter, however, are only suitable for post-menopausal patients.
Predominantly used for stage 2 – 4 cancers, and are particularly beneficial in Estrogen receptor negative (ER-) disease. They are normally given in combinations – usually for 3 to 6 months. One of the most common treatments is cyclophosphamide plus doxorubicin (Adriamycin ) known as “AC”. Most chemotherapy medications work by destroying fast-growing and/or fast-replicating cancer cells either by causing DNA damage upon replication or other mechanisms; the drawback is that these drugs also damage fast-growing normal cells where they can cause serious side effects. Damage to the heart muscle is the most common dangerous complication of doxorubicin . In some cases a taxane drug, such as docetaxe l, is added, and the regime is then known as CAT. The taxane attacks the microtubules in cancer cells. Another common treatment, which produces equivalent results, is cyclophosphamide , methotrexate , and fluorouracil (CMF).
Monoclonal antibodies :
This is a relatively new development in HER2 breast cancer treatment. In approximately fifteen to twenty percent (15 to 20%) of breast cancer cases have amplification of the HER2/neu gene or over-expression of its protein product. This receptor is normally stimulated by a growth factor which causes the cell to divide; in the absence of the growth factor, the cell will normally stop growing. Over-expression of this receptor in breast cancer is associated with increased disease recurrence and a worse prognosis. Herceptin, a monoclonal antibody to HER2, has improved the five-year (5 year) survival rate
Radiotherapy is given after surgery to the region of the tumor bed (pictured at left) and regional lymph nodes, to destroy microscopic tumor cells that may have escaped surgery. It can also have a beneficial effect on tumor micro-environment. Radiation therapy can be delivered either as external beam therapy or as brachytherapy (internal radiotherapy). Conventionally, radiotherapy is given after surgery for breast cancer, however, it can also be given at the time of the surgery intraoperatively. In clinical trials of providing the radiation during surgery, it was found to be as effective at four-years (4-years) as the conventional several weeks of whole breast external beam radiotherapy. Radiation therapy can reduce the risk of recurrence by 50 – 66% (1/2 – 2/3 reduction of risk) when delivered in the correct dose and is considered essential when the cancer is treated by removing only the lump.
Prognosis of breast cancer
Diagram of major lymph nodes in the human body
A prognosis is a prediction of outcome as well as the probability of progression-free survival (PFS) or disease-free survival (DFS). They are based on experience with breast cancer patients who had similar classification. The prognosis is an estimate – as patients with the same classification will often survive different lengths of time and the classifications are not always precise. Survival is usually calculated as an average number of months (or years) that fifty-percent (50%) of patients survive, or the percentage of patients that are alive after one (1), five (5), fifteen (15), and twenty (20) years. Prognosis is important for treatment decisions as patients with a good prognosis are offered less invasive treatments such as lumpectomy and radiation, while patients with a poorer prognosis are usually offered more aggressive treatments.
Prognostic factors are reflected in the classification scheme for breast cancer including stage (i.e., tumor size, location, whether disease has spread to lymph nodes and other parts of the body), grade, recurrence of the disease as well as the age and overall health of the patient.
The stage of the breast cancer is the most important component of traditional classification methods because it has a greater effect on the prognosis than other considerations. Staging takes into consideration size, local involvement, lymph node status, and whether metastatic disease is present. The higher the stage at diagnosis, the poorer the prognosis will be. The stage is raised by the invasiveness of disease to either the lymph nodes, chest wall, skin, or beyond and the aggressiveness of the cancer cells. The stage is lowered by the presence of cancer-free zones as well as close-to-normal behavior (grading). Size is not a factor in staging unless the cancer is invasive.
The grade of breast cancer is assessed by comparison of the breast cancer cells to normal cells. The closer-to-normal the cancer cells are, the slower their growth and the better the prognosis. If they aren’t well differentiated, they will appear immature, will divide more rapidly, and will tend to spread.