Chemotherapy:

Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by injection. They work systemically by killing cancer cells throughout the body. (Unfortunately, they also kill normal cells, which accounts for many of their side effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to treat types of early-stage breast cancer.

Newer biologic drugs target specific proteins involved in cancer. Because they do not work as systemically as chemotherapy or hormone therapy drugs, they tend to cause fewer widespread side effects, although they also carry risks of their own

Chemotherapy needs to be tailored to the type of cancer involved. Women require different treatments depending on whether the tumor is node-negative or -positive, hormone receptor-positive or -negative, or HER2-positive or -negative. Different treatment approaches are also used for early-stage cancer and advanced cancer.

In general, women with hormone receptor-negative cancers respond better to chemotherapy than women with hormone receptor-positive cancer. However, some women with hormone receptor-positive cancer do benefit from chemotherapy, as well as from hormone therapy.

Adjuvant chemotherapy is administered following surgery and before radiation therapy. Delaying chemotherapy until more than 12 weeks after surgery may increase the risk for breast cancer recurrence and reduce the odds for survival.

Chemotherapy Drug Classes

Many different types of chemotherapy drugs are used to treat breast cancer. Common types of chemotherapy drug classes include:

• Anthracyclines include doxorubicin (Adriamycin) and epirubicin (Ellence). Anthracycline-based combination regimens are often used to treat early-stage breast cancer, as well as advanced cancer.
• Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). These drugs may be particularly helpful for node-positive breast cancer. A newer formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced breast cancer.
• Platinum-based drugs include oxaliplatin (Eloxatin) and carboplatin (Paraplatin). These drugs may be used in combination regiments for advanced cancer or for cancers associated with BRCA genes.

Chemotherapy Regimens for Early-Stage Breast Cancer

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug classes rather than drug names. For example, regimens that contain an anthracycline drug (such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy regimens.

Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months. Common chemotherapy regimens for early-stage breast cancer include:

• AC (Doxorubicin and cyclophosphamide)
• AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
• CAF (Cyclophosphamide, doxorubicin, and 5-FU)
• CMF (Cyclophosphamide, methotrexate, and 5-FU)
• TAC (Docetaxel, doxorubicin, and cyclophosphamide)

Targeted Therapy for Early-Stage HER2-Positive Breast Cancer

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody that targets the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage breast cancer and are associated with more aggressive disease. Younger women tend to be most affected. In 2006, the Food and Drug Administration approved trastuzumab for treatment of HER2-positive, early-stage breast cancer (cancer confined to the breasts or lymph nodes that has been surgically removed).

Trastuzumab is given along with other chemotherapy drugs following lumpectomy or mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and death among women with early-stage breast cancer, but it increases the risk of heart problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to have regular heart monitoring, especially if they have already have heart problems.

Chemotherapy for Advanced (Metastatic) Cancer

Patients who develop metastatic disease (cancer that spreads throughout the body) are generally not curable. New advances in drug therapies, however, can help shrink tumors, prolong survival, and improve quality of life.

Chemotherapy regimens for advanced cancer may use a single drug or a combination of drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for advanced breast cancer. Some specific combinations for advanced cancer include:

• Gemcitabine and paclitaxel. In 2004, the Food and Drug Administration approved the antimetabolite drug gemcitabine (Gemzar) for use in combination with paclitaxel (Taxol) as a first-line treatment option for women with metastatic breast cancer.
• Capecitabine (Xeloda) and docetaxel (Taxotere). Capecitabine is an oral drug that is chemically related to 5-FU. It is also being studied in combination with many other drugs. In 2007, the FDA approved a new type of drug, ixabepilone (Ixempra), for use in combination with capecitabine in patients with advanced breast cancer that have not responded to other types of chemotherapy.

Numerous chemotherapy drugs and drug combinations are being tested in clinical trials. Patients with advanced breast cancer may also receive other types of drug treatments. Bisphosphonate drugs, such as zoledronic acid (Zometa) and pamidronate (Aredia), are important supportive drugs for preventing fractures and reducing pain in people whose cancer has spread to the bones.

Targeted Therapy for Advanced HER2-Positive Breast Cancer

Three targeted therapy drugs are approved for the treatment of HER2-positive advanced breast cancer

• Trastuzumab (Herceptin) was approved in 1998 for treatment of metastatic breast cancer. It is used in adjuvant chemotherapy, along with drugs such as paclitaxel.
• Lapatinib (Tykerb) was approved in 2007 for patients who have not been helped by other cancer drugs, including an anthracycline, a taxane, or trastuzumab. Lapatinib is used in combination with capecitabine (Xeloda). Research suggests it may have fewer risks for heart problems than trastuzumab.
• Bevacizumab (Avastin) was approved in 2008 for treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer. Studies indicate that bevacizumab does not help prolong overall survival, but may help slow tumor growth. Bevacizumab is used in combination with paclitaxel. Bevacizumab targets vascular endothelial growth factor (VEGF), a protein involved in tumor blood vessel formation (angiogenesis).

Investigational Drugs

Promising new treatments for breast cancer include:

• Zoledronic acid (Zometa) is an intravenous bisphosphonate drug that is used to help prevent or delay bone fractures in patients with breast cancer that has spread to the bones. Recent research suggests that the drug may also help reduce the risk for cancer recurrence in patients with early-stage breast cancer.

Side Effects of Chemotherapy

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include:

• Nausea and vomiting. Drugs such as ondansetron (Zofran) and aprepitant (Emend) can help relieve these side effects.
• Diarrhea
• Temporary hair loss
• Weight loss
• Fatigue
• Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. They include the following:

• Anemia. Chemotherapy-induced anemia is usually treated with erythropoiesis-stimulating drugs, which include epoietin alfa (Epogen, Procrit) and darberpetin alfa (Aranesp). Erythropoiesis-stimulating drugs should not be used unless a patientâ ' s hemoglobin level drops to below 10 g/dL. These drugs may pose serious health risks when they are used to achieve a hemoglobin level of 12 g/dL or greater. Doctors need to follow strict dosing guidelines when administering these drugs. Patients should discuss the risks and benefits of erythropoiesis-stimulating drugs with their oncologists. [For more information, see In-Depth Report #57: Anemia.]
• Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection.
• Liver and kidney damage.
• Abnormal blood clotting (thrombocytopenia).
• Allergic reaction, particularly to platinum-based drugs.
• Menstrual abnormalities and infertility. Premature menopause occurs in about 30% of women, particularly in those over 40. A natural hormone medication called a gonadotropin-releasing hormone analogue, which puts women in a temporary pre-pubescent state during chemotherapy, may preserve fertility in some women. Women may also wish to consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro fertilization and freezing of embryos for later use. The American Society of Clinical Oncology recommends that women being treated for cancer see a reproductive specialist to discuss all available fertility preservation options.
• Sexual dysfunction.
• Rarely, secondary cancers such as leukemia.
• A quarter to a third of women report problems in concentration, motor function, and memory, which can be long-term.
• Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure, particularly in women with pre-existing risk factors. Cumulative doses of anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time and increase the risk for heart failure.
• Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur, more often in taxol than taxotere. Taking a steroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, relievable with corticosteroids.

High-Dose Chemotherapy with Bone Marrow or Peripheral-Blood Stem Cell Transplantation

High-dose chemotherapy along with peripheral-blood stem cell rescue or bone marrow transplantation procedures have been used for cancer that has metastasized and, in some cases, for earlier stages of breast cancer in high-risk patients. The objective of this treatment is to be able to give patients very high toxic doses of cell-killing drugs.

Transplantation procedures are based on stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments can harm these growing cells as well as cancer cells.

Despite the initial enthusiasm over the use of transplantation therapy for treatment of high risk breast cancer, this approach is no longer generally recommended and is rarely used outside of a clinical trial setting.