CIENCIASMEDICASNEWS: Breast Cancer Treatment (PDQ®) 2/3 —Patient Version

Breast Cancer Treatment (PDQ®)—Patient Version - National Cancer Institute

The grading system is used to describe how quickly a breast tumor is likely to grow and spread.

The grading system describes a tumor based on how abnormal the cancer cells and tissue look under a microscope and how quickly the cancer cells are likely to grow and spread. Low-grade cancer cells look more like normal cells and tend to grow and spread more slowly than high-grade cancer cells. To describe how abnormal the cancer cells and tissue are, the pathologist will assess the following three features:

How much of the tumor tissue has normal breast ducts.
The size and shape of the nuclei in the tumor cells.
How many dividing cells are present, which is a measure of how fast the tumor cells are growing and dividing.

For each feature, the pathologist assigns a score of 1 to 3; a score of “1” means the cells and tumor tissue look the most like normal cells and tissue, and a score of “3” means the cells and tissue look the most abnormal. The scores for each feature are added together to get a total score between 3 and 9.

Three grades are possible:

Total score of 3 to 5: G1 (Low grade or well differentiated).
Total score of 6 to 7: G2 (Intermediate grade or moderately differentiated).
Total score of 8 to 9: G3 (High grade or poorly differentiated).

Biomarker testing is used to find out whether breast cancer cells have certain receptors.

Healthy breast cells, and some breast cancer cells, have receptors (biomarkers) that attach to the hormones estrogen and progesterone. These hormones are needed for healthy cells, and some breast cancer cells, to grow and divide. To check for these biomarkers, samples of tissue containing breast cancer cells are removed during a biopsy or surgery. The samples are tested in a laboratory to see whether the breast cancer cells have estrogen or progesterone receptors.

Another type of receptor (biomarker) that is found on the surface of all breast cancer cells is called HER2. HER2 receptors are needed for the breast cancer cells to grow and divide.

For breast cancer, biomarker testing includes the following:

Estrogen receptor (ER). If the breast cancer cells have estrogen receptors, the cancer cells are called ER positive (ER+). If the breast cancer cells do not have estrogen receptors, the cancer cells are called ER negative (ER-).
Progesterone receptor (PR). If the breast cancer cells have progesterone receptors, the cancer cells are called PR positive (PR+). If the breast cancer cells do not have progesterone receptors, the cancer cells are called PR negative (PR-).
Human epidermal growth factor type 2 receptor (HER2/neu or HER2). If the breast cancer cells have larger than normal amounts of HER2 receptors on their surface, the cancer cells are called HER2 positive (HER2+). If the breast cancers cells have a normal amount of HER2 on their surface, the cancer cells are called HER2 negative (HER2-). HER2+ breast cancer is more likely to grow and divide faster than HER2- breast cancer.

Sometimes the breast cancer cells will be described as triple negative or triple positive.

Triple negative. If the breast cancer cells do not have estrogen receptors, progesterone receptors, or a larger than normal amount of HER2 receptors, the cancer cells are called triple negative.
Triple positive. If the breast cancer cells do have estrogen receptors, progesterone receptors, and a larger than normal amount of HER2 receptors, the cancer cells are called triple positive.

It is important to know the estrogen receptor, progesterone receptor, and HER2 receptor status to choose the best treatment. There are drugs that can stop the receptors from attaching to the hormones estrogen and progesterone and stop the cancer from growing. Other drugs may be used to block the HER2 receptors on the surface of the breast cancer cells and stop the cancer from growing.

The TNM system, the grading system, and biomarker status are combined to find out the breast cancer stage.

Here are 3 examples that combine the TNM system, the grading system, and the biomarker status to find out the Pathological Prognostic breast cancer stage for a woman whose first treatment was surgery:

If the tumor size is 30 millimeters (T2), has not spread to nearby lymph nodes (N0), has not spread to distant parts of the body (M0), and is:

Grade 1
HER2+
ER-
PR-

The cancer is stage IIA.

If the tumor size is 53 millimeters (T3), has spread to 4 to 9 axillary lymph nodes (N2), has not spread to other parts of the body (M0), and is:

Grade 2
HER2+
ER+
PR-

The tumor is stage IIIA.

If the tumor size is 65 millimeters (T3), has spread to 3 axillary lymph nodes (N1a), has spread to the lungs (M1), and is:

Grade 1
HER2+
ER-
PR-

The cancer is stage IV.

Talk to your doctor to find out what your breast cancer stage is and how it is used to plan the best treatment for you.

After surgery, your doctor will receive a pathology report that describes the size and location of the primary tumor, the spread of cancer to nearby lymph nodes, tumor grade, and whether certain biomarkers are present. The pathology report and other test results are used to determine your breast cancer stage.

You are likely to have many questions. Ask your doctor to explain how staging is used to decide the best options to treat your cancer and whether there are clinical trials that might be right for you.

The treatment of breast cancer depends partly on the stage of the disease.

For ductal carcinoma in situ (DCIS) treatment options, see Ductal Carcinoma in Situ.

For treatment options for stage I, stage II, stage IIIA, and operable stage IIIC breast cancer, see Early, Localized, or Operable Breast Cancer.

For treatment options for stage IIIB, inoperable stage IIIC, and inflammatory breast cancer, see Locally Advanced or Inflammatory Breast Cancer.

For treatment options for cancer that has recurred near the area where it first formed, see Locoregional Recurrent Breast Cancer.

For treatment options for stage IV breast cancer or breast cancer that has recurred in other parts of the body, see Metastatic Breast Cancer.

Inflammatory Breast Cancer

In inflammatory breast cancer, cancer has spread to the skin of the breast and the breast looks red and swollen and feels warm. The redness and warmth occur because the cancer cells block the lymph vessels in the skin. The skin of the breast may also show the dimpled appearance called peau d’orange (like the skin of an orange). There may not be any lumps in the breast that can be felt. Inflammatory breast cancer may be stage IIIB, stage IIIC, or stage IV.

Recurrent Breast Cancer

Recurrent breast cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the breast, in the skin of the breast, in the chest wall, or in nearby lymph nodes.

Treatment Option Overview

KEY POINTS

There are different types of treatment for patients with breast cancer.
Five types of standard treatment are used:
- Surgery
- Radiation therapy
- Chemotherapy
- Hormone therapy
- Targeted therapy
Treatment for breast cancer may cause side effects.
Patients may want to think about taking part in a clinical trial.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Follow-up tests may be needed.

There are different types of treatment for patients with breast cancer.

Different types of treatment are available for patients with breast cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

Most patients with breast cancer have surgery to remove the cancer.

Sentinel lymph node biopsy is the removal of the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node in a group of lymph nodes to receive lymphatic drainage from the primary tumor. It is the first lymph node the cancer is likely to spread to from the primary tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymph ducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views the tissueunder a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes. Sometimes, a sentinel lymph node is found in more than one group of nodes. After the sentinel lymph node biopsy, the surgeon removes the tumor using breast-conserving surgery or mastectomy. If cancer cells were found, more lymph nodes will be removed through a separate incision. This is called a lymph node dissection.

Types of surgery include the following:

Breast-conserving surgery is an operation to remove the cancer and some normal tissue around it, but not the breast itself. Part of the chest wall lining may also be removed if the cancer is near it. This type of surgery may also be called lumpectomy, partial mastectomy, segmental mastectomy, quadrantectomy, or breast-sparing surgery.
ENLARGE
Breast-conserving surgery. The tumor and some normal tissue around it are removed, but not the breast itself. Some lymph nodes under the arm may be removed. Part of the chest wall lining may also be removed if the cancer is near it.
Total mastectomy: Surgery to remove the whole breast that has cancer. This procedure is also called a simple mastectomy. Some of the lymph nodes under the arm may be removed and checked for cancer. This may be done at the same time as the breast surgery or after. This is done through a separate incision.
ENLARGE
Total (simple) mastectomy. The dotted line shows where the entire breast is removed. Some lymph nodes under the arm may also be removed.
Modified radical mastectomy: Surgery to remove the whole breast that has cancer, many of the lymph nodes under the arm, the lining over the chest muscles, and sometimes, part of the chest wall muscles.
ENLARGE
Modified radical mastectomy. The dotted line shows where the entire breast and some lymph nodes are removed. Part of the chest wall muscle may also be removed.

Chemotherapy may be given before surgery to remove the tumor. When given before surgery, chemotherapy will shrink the tumor and reduce the amount of tissue that needs to be removed during surgery. Treatment given before surgery is called preoperative therapy or neoadjuvant therapy.

After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given radiation therapy, chemotherapy, targeted therapy, or hormone therapy after surgery, to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called postoperative therapy or adjuvant therapy.

If a patient is going to have a mastectomy, breast reconstruction (surgery to rebuild a breast’s shape after a mastectomy) may be considered. Breast reconstruction may be done at the time of the mastectomy or at some time after. The reconstructed breast may be made with the patient’s own (nonbreast) tissue or by using implants filled with saline or silicone gel. Before the decision to get an implant is made, patients can call the Food and Drug Administration's (FDA) Center for Devices and Radiologic Health at 1-888-INFO-FDA (1-888-463-6332) or visit the FDA website for more information on breast implants.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

External radiation therapy uses a machine outside the body to send radiation toward the cancer.
Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy is used to treat breast cancer. Internal radiation therapy with strontium-89 (a radionuclide) is used to relieve bone pain caused by breast cancer that has spread to the bones. Strontium-89 is injected into a vein and travels to the surface of the bones. Radiation is released and kills cancer cells in the bones.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).

The way the chemotherapy is given depends on the type and stage of the cancer being treated. Systemic chemotherapy is used in the treatment of breast cancer.

See Drugs Approved for Breast Cancer for more information.

Hormone therapy

Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormones are substances made by glands in the body and circulated in the bloodstream. Some hormones can cause certain cancers to grow. If tests show that the cancer cells have places where hormones can attach (receptors), drugs, surgery, or radiation therapy is used to reduce the production of hormones or block them from working. The hormone estrogen, which makes some breast cancers grow, is made mainly by the ovaries. Treatment to stop the ovaries from making estrogen is called ovarian ablation.

Hormone therapy with tamoxifen is often given to patients with early localized breast cancer that can be removed by surgery and those with metastatic breast cancer (cancer that has spread to other parts of the body). Hormone therapy with tamoxifen or estrogens can act on cells all over the body and may increase the chance of developing endometrialcancer. Women taking tamoxifen should have a pelvic exam every year to look for any signs of cancer. Any vaginal bleeding, other than menstrual bleeding, should be reported to a doctor as soon as possible.

Hormone therapy with a luteinizing hormone-releasing hormone (LHRH) agonist is given to some premenopausal women who have just been diagnosed with hormone receptor positive breast cancer. LHRH agonists decrease the body's estrogen and progesterone.

Hormone therapy with an aromatase inhibitor is given to some postmenopausal women who have hormone receptor positive breast cancer. Aromatase inhibitors decrease the body's estrogen by blocking an enzyme called aromatase from turning androgen into estrogen. Anastrozole, letrozole, and exemestane are types of aromatase inhibitors.

For the treatment of early localized breast cancer that can be removed by surgery, certain aromatase inhibitors may be used as adjuvant therapy instead of tamoxifen or after 2 to 3 years of tamoxifen use. For the treatment of metastatic breast cancer, aromatase inhibitors are being tested in clinical trials to compare them to hormone therapy with tamoxifen.

In women with hormone receptor positive breast cancer, at least 5 years of adjuvant hormone therapy reduces the risk that the cancer will recur (come back).

Other types of hormone therapy include megestrol acetate or anti-estrogen therapy such as fulvestrant.

See Drugs Approved for Breast Cancer for more information.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibodies, tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and PARP inhibitors are types of targeted therapies used in the treatment of breast cancer.

Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Monoclonal antibodies may be used in combination with chemotherapy as adjuvant therapy.

Types of monoclonal antibody therapy include the following:

Trastuzumab is a monoclonal antibody that blocks the effects of the growth factor protein HER2, which sends growth signals to breast cancer cells. It may be used with other therapies to treat HER2 positive breast cancer.
Pertuzumab is a monoclonal antibody that may be combined with trastuzumab and chemotherapy to treat breast cancer. It may be used to treat certain patients with HER2 positive breast cancer that has metastasized (spread to other parts of the body). It may also be used as neoadjuvant therapy in patients with locally advanced, inflammatory, or early-stage breast cancer. It may also be used as adjuvant therapy in certain patients with early-stage HER2 positive breast cancer.
Ado-trastuzumab emtansine is a monoclonal antibody linked to an anticancer drug. This is called an antibody-drug conjugate. It is used to treat HER2 positive breast cancer that has spread to other parts of the body or recurred (come back).

Tyrosine kinase inhibitors are targeted therapy drugs that block signals needed for tumors to grow. Tyrosine kinase inhibitors may be used with other anticancer drugs as adjuvant therapy. Tyrosine kinase inhibitors include the following:

Lapatinib is a tyrosine kinase inhibitor that blocks the effects of the HER2 protein and other proteins inside tumor cells. It may be used with other drugs to treat patients with HER2 positive breast cancer that has progressed after treatment with trastuzumab.
Neratinib is a tyrosine kinase inhibitor that blocks the effects of the HER2 protein and other proteins inside tumor cells. It may be used to treat patients with early-stage HER2 positive breast cancer after treatment with trastuzumab.

Cyclin-dependent kinase inhibitors are targeted therapy drugs that block proteins called cyclin-dependent kinases, which cause the growth of cancer cells. Cyclin-dependent kinase inhibitors include the following:

Palbociclib is a cyclin-dependent kinase inhibitor used with the drug letrozole to treat breast cancer that is estrogen receptor positive and HER2 negative and has spread to other parts of the body. It is used in postmenopausal women whose cancer has not been treated with hormone therapy. Palbociclib may also be used with fulvestrant in women whose disease has gotten worse after treatment with hormone therapy.
Ribociclib is a cyclin-dependent kinase inhibitor used with letrozole to treat breast cancer that is hormone receptor positive and HER2 negative and has come back or spread to other parts of the body. It is used in postmenopausal women whose cancer has not been treated with hormone therapy. It is also used with fulvestrant in postmenopausal women with hormone receptor positive and HER2 negative breast cancer that has spread to other parts of the body or has recurred. It is also used in premenopausal women with hormone receptor positive and HER2 negative breast cancer that has spread to other parts of the body or has recurred.
Abemaciclib is a cyclin-dependent kinase inhibitor used to treat hormone receptor positive and HER2 negative breast cancer that is advanced or has spread to other parts of the body. It may be used alone or with other drugs.

Mammalian target of rapamycin (mTOR) inhibitors block a protein called mTOR, which may keep cancer cells from growing and prevent the growth of new blood vessels that tumors need to grow. mTOR inhibitors include the following:

Everolimus is an mTOR inhibitor used in postmenopausal women with advancedhormone receptor positive breast cancer that is also HER2 negative and has not gotten better with other treatment.

PARP inhibitors are a type of targeted therapy that block DNA repair and may cause cancer cells to die. PARP inhibitors include the following:

Olaparib is a PARP inhibitor used to treat patients with mutations in the BRCA1 or BRCA2genes and HER2 negative breast cancer that has spread to other parts of the body. PARP inhibitor therapy is being studied for the treatment of patients with triple negative breast cancer.
Talazoparib is a PARP inhibitor used to treat patients with mutations in the BRCA1 or BRCA2 genes and HER2 negative breast cancer that is locally advanced or has spread to other parts of the body.