Types of Medication

Chemotherapy

Chemotherapeutic drugs (chemotherapy) are anti-cancer therapies delivered directly to the bloodstream (intravenously) or swallowed as pills or capsules. They can also be given by shot in the muscle or just under the skin. These drugs are directed against known tumors in the primary site (breast) or secondary sites (metastases) outside of the breast or when metastasis is suspected but not identified. Chemotherapy is given in cycles of two, three or four weeks, followed by a rest period. Side effects are due to the toxicity to noncancerous cells, such as those found in hair follicles, in the lining of the colon and in bone marrow cells. Thus, common side effects include hair loss, nausea, fatigue and a susceptibility to infections when the blood counts (white cells) are low. Drugs are available to treat these side effects, including growth factors that help the bone marrow generate new healthy cells.

Chemotherapy generally is used in the following cases:

• For breast cancer that has spread to lymph nodes or other organs.
• For breast tumors that are locally invasive even if there are no known metastases. "Adjuvant chemotherapy," given after surgery to remove any remaining microscopic breast cancer cells, reduces the risk of recurrence. "Neoadjuvant chemotherapy" is given before surgery to try to shrink the breast cancer.
• For recurrent breast cancer.

Different chemotherapy drugs (and combinations of drugs) are used depending on the kind of breast cancer, its stage and the health status of the patient. There are several classes of chemotherapy drugs, each of which attacks a certain feature of a given cancer cell. Multiple chemotherapeutic agents are more effective than using a single drug, because a wider variety of cancer cell features are targeted at one time. The following list of chemotherapeutic combinations may not be complete. It is intended to give you some background information only. Talk to your doctor about whether chemotherapy is right for you and which combination would be most appropriate.

Adjuvant chemotherapy options for women with negative nodes:

• CMF - cyclophosphamide/methotrexate/fluorouracil
• FAC/CAF - fluorouracil/doxorubicin/cyclophosphamide
• AC - doxorubicin/cyclophosphamide
• AC-T - doxorubicin/cyclophosphamide/paclitaxel
• TAC - doxorubicin/cyclophosphamide/docetaxel
• Herceptin - in combination with chemotherapy (i.e., AC-T)

Adjuvant chemotherapy options for women with positive nodes:

• FAC/CAF - fluorouracil/doxorubicin/cyclophosphamide
• FEC/CEF - cyclophosphamide/epirubicin/fluorouracil
• AC - doxorubicin/cyclophosphamide
• AC-T - doxorubicin/cyclophosphamide + paclitaxel
• EC - epirubicin/cyclophosphamide
• TAC - docetaxel/doxorubicin/cyclophosphamide
• CMF - cyclophosphamide/methotrexate/fluorouracil
• Herceptin - in combination with chemotherapy (i.e. AC-T)

Preferred single agents for the treatment of recurrent or metastatic breast cancer:

• Anthracyclines (doxorubicin or epirubicin)
• Taxanes (paclitaxel or docetaxel)
• Capecitabine
• Vinorelbine
• Herceptin
• CAF/FAC - fluorouracil/doxorubicin/cyclophosphamide
• FEC/CEF - cyclophosphamide/epirubicin/fluorouracil
• AC - doxorubicin/cyclophosphamide
• EC - epirubicin/cyclophosphamide
• AT - doxorubicin/docetaxel or doxorubicin/paclitaxel
• CMF - cyclophosphamide/methotrexate/fluorouracil
• Docetaxel/capecitabine
• Gemcitabine + cisplatin or carboplatin

Other active drugs for the treatment of recurrent or metastatic breast cancer:

• Gemcitabine
• Platinum drugs (cisplatin or carboplatin)
• Epirubicin
• Etoposide
• Vinblastine
• Fluorouracil
• Mitomycin C

Hormone Therapy

Estrogen/progesterone (ER/PR). Some breast tumors cells, like normal breast cells, respond to hormones such as estrogen and progesterone (ER/PR). These cells have ER/PR receptors where hormone molecules "land" and trigger cell growth. The pathologist would identify these "ER/PR positive" cells in the breast tumor specimen removed at surgery. Breast glands normally mature and produce milk in response to hormones. ER/PR positive breast cancer cells spread, either in the breast or wherever they have metastasized (spread) in response to hormones.

Selective estrogen receptor modulators (SERMs). These are tamoxifen, toremifene, and raloxifene. Tamoxifen is an effective treatment given in ER/PR positive breast cancer to help prevent breast cancer recurrence or to prevent the growth of a new breast tumor.

Estrogen receptor down regulators (ERDs). These drugs slow down or stop the growth of breast cancer cells by blocking or breaking down the hormone receptors. They are used as second line therapy when tamoxifen is ineffective. Fulvestrant is an ERD monthly injection approved by the U.S. Food and Drug Administration and is as effective as SERMs.

Aromatase inhibitors (AIs). These agents are only effective in postmenopausal women who still produce some estrogen, but only by conversion of testosterone into estrogen outside the ovaries. Even this small amount of estrogen stimulates the growth of ER/PR positive cancer cells, so the selective blockade of non-ovarian estrogen production is most helpful in postmenopausal patients. Arimidex® (chemical name: anastrozole), Femara® (letrozole), and Aromasin® (exemestane) are the aromatase inhibitors in current use. They are all similarly effective. They are used in postmenopausal women after surgery (adjuvant hormonal therapy) for ER/PR positive breast cancer to try to kill off any remaining microscopic breast cancer cells in the body or before surgery (neoadjuvant hormonal therapy) to try to shrink the ER/PR positive breast tumors. They are also used in postmenopausal women with ER/PR positive breast cancer that have spread (metastasized) to distant sites outside of the breast and therefore cannot be resected by surgery. They can also be used in premenopausal women who are made postmenopausal by monthly injections of a LHRH agonist (Lupron® or Zoladex®).

Aromatase inhibitors have been shown in studies to work at least as well as tamoxifen in preventing breast cancer from coming back in postmenopausal women. Based on these studies, many doctors recommend these drugs as the first choice for adjuvant hormonal therapy.

Aromatase inhibitors are linked to fewer cases of ovarian cancer and blood clots than tamoxifen. However, they increase the chance of getting osteoporosis and fractures. And can cause hot flashes and joint pain.

Ovarian suppression. Ovarian suppression is used in premenopausal women with ER/PR positive breast cancer to induce menopause in order to eliminate any estrogen production by their ovaries. Estrogen made by the ovaries in premenopausal women stimulates the growth of ER/PR positive breast cancer tumors. Ovarian suppression is achieved by using an injection of an LHRH (leutenizing hormone releasing hormone) agonist such as goserilin (Zoladex) or leuprolide (Lupron) which causes the brain to stop telling the ovaries to make estrogen. LHRH agonists are usually given once per month to once per year, depending on which drug is used. Ovarian suppression is used in premenopausal women after surgery (adjuvant ovarian suppression) for ER/PR positive breast cancer to try to kill off any remaining microscopic breast cancer cells in the body. They are also used in premenopausal women with ER/PR positive breast cancer that has spread (metastasized) to distant sites outside of the breast and therefore cannot be resected by surgery.

Monoclonal antibody therapy. About 25 percent of breast cancer cells have a mutant (abnormal) gene that makes too many receptors for a protein called HER-2/neu. Receptors on a cell surface, like a roof antennae, receive chemical signals activating certain cell functions. Too many cell surface HER-2/neu receptors make breast cancer cells grow too fast and divide too frequently. Trastuzumab (Herceptin®) is a monoclonal antibody drug that is used to treat breast cancer with HER-2/neu positive cells. The FDA has approved trastuzumab for use in metastatic breast cancer. Recently, large clinical trials have shown that trastuzumab (when used in combination with chemotherapy (AC-T) increases the disease-free survival and overall survival of patients with HER-2/neu overproducing breast cancer after surgery (adjuvant therapy).

It has been found that new blood vessel formation (angiogenesis) is vital to the growth of many cancers, including breast cancer. VEGF is a very important protein (molecule) involved in angiogenesis and therefore cancer growth. Bevacizumab (Avastin) is a monoclonal antibody that targets and blocks VEGF and therefore blocks tumor blood vessel formation. A recent clinical trial showed that bevacizumab (when used in combination with chemotherapy with paclitaxel) increased the response rate (rate of tumor shrinkage) and progression-free survival in patients with breast cancer that has spread (metastasized) outside the breast compared to chemotherapy with paclitaxel alone.

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This article was reviewed and updated June 2007.