Treatment

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Chemotherapy Regimens and Drug Combinations. // Adjuvant chemotherapy is usually administered after initial surgery in combination regimens in four to six courses of treatment over 3 - 6 months and usually before follow-up radiation therapy to the breast. The following are some important drugs used in combination treatments: Patients who develop metastatic disease (cancer that spreads throughout the body) are generally not curable. Combination therapies, however, are often effective at shrinking tumors and improving quality of life. In some cases, such therapies may improve survival. These drug regimens usually combine a taxane drug, such as docetaxel (Taxotere) or paclitaxel (Taxol), with an anthracycline drug, such as doxorubicin (Adriamycin) or epirubicin (Ellence). Other promising combinations and single drugs include: Other drugs showing promise in chemotherapeutic regimens for metastatic cancer include bevacizumab (Avastin), vinorelbine (Navelbine), pemetrexed (Alimta), gemcitabine (Gemzar), edatrexate, losoxantrone, and platinum-based drugs (cisplatin, carboplatin, oxaplatin). //Bisphosphonates. // Bisphosphonates (Zometa, Aredia) are important supportive drugs for preventing fractures and reducing pain in people whose cancer has spread to the bones. Clodronate and pamidronate are the drugs currently used, and newer bisphosphonates (ibandronate and zoledronate) are being studied. To date, evidence strongly supports their use for reducing pain and improving quality of life. Bisphosphonates are also being investigated in early-stage breast cancer, with some studies suggesting that they may help prevent metastasis in the bone and improve survival rates. 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: Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. They include the following: 
 * Anthracyclines. Anthracyclines include doxorubicin (Adriamycin) or epirubicin (Ellence). To date, combinations using these drugs have the best survival benefits. Patients who overexpress the HER-2/neu gene and have hormone receptor-negative tumors may particularly benefit from anthracyclines. The drug may have toxic effects on the heart, however.
 * Cyclophosphamide, 5-fluorouracil (5-FU), and methotrexate (CMF). This was the standard regimen for years, but its use has declined with the introduction of anthracyclines. A variation in which mitoxantrone (Novantrone) replaced methotrexate may offer better survival rates than CMF.
 * Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). Two studies published in 2003 suggested that women should strongly consider taxane-based therapy for node-positive breast cancer. The first study compared the standard regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) to the combination of docetaxel (Taxotere), doxorubicin (Adriamycin), and cyclophosphamide (Cytoxan) (TAC). After 55 months of follow-up, TAC-treated patients had a 28% lower risk of relapse and a 30% lower mortality rate than FAC-treated patients. In the second study, TAC therapy given on a dose-dense schedule (every 2 weeks) was shown to be superior to a standard schedule (every 3 weeks).
 * An injectable suspension form of paclitaxel (Abraxane) uses a novel technology to deliver chemotherapy to the tumor site. In a 2003 study, Abraxane increased the efficacy of paclitaxel by doubling the response rate (33% vs. 19%) and significantly prolonging the time to tumor progression. Abraxane is associated with fewer side effects than paclitaxel, and does not require pretreatment with a steroid. It was approved by the FDA in 2005.
 * Trastuzumab (Herceptin). Trastuzumab is a humanized monoclonal antibody that targets the HER2 protein. (Targeted therapies are increasingly showing promise for treating many forms of cancer.) Research supports that trastuzumab, a drug used to treat metastatic breast cancer, is also an important treatment for early-stage, HER 2-positive breast cancer. Trastuzumab is given either along with or following adjuvant chemotherapy. Data from 2005 and 2006 indicate that trastuzumab and paclitaxel plus standard adjuvant chemotherapy (such as doxorubicin and cyclophosphamide) prolongs disease-free survival and reduces the risk of cancer recurrence for these patients. Most of the study patients had cancer that had spread to the lymph nodes (lymph-node positive cancer). In a 2005 study, patients in the trastuzumab treatment group had a 52% reduction in disease recurrence compared with those not treated with the drug. Trastuzumab can cause heart failure and other heart function problems, which can usually be controlled with medication. Women who take trastuzumab need to have regular cardiac monitoring, especially if they have pre-existing heart problems.
 * Chemotherapy and Other Drugs Used in Metastatic Cancer **
 * Cyclophosphamide, 5-fluorouracil (5-FU), and methotrexate (CMF) with a corticosteroid (such as prednisone).
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Capecitabine (Xeloda). This is an oral drug that is sometimes used as a substitute for 5-FU or CMF, especially in older patients. Studies have reported response rates of up to 26% in patients previously treated with chemotherapy and of 30% when used as the first treatment for metastatic breast cancer. Capecitabine is also showing good results in combination with lapatinib (Tykerb) in treating women with advanced HER2 positive cancer that did not improve with trastuzumab therapy. As a result, in March 2007, the Food and Drug Administration approved this combination treatment for patients whose cancer failed to respond to trastuzumab.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Trastuzumab (Herceptin). Trastuzumab destroys cells carrying the HER2 protein, and is being used in women who test positive for the gene that regulates this protein. HER2 plays a role in cancer cell growth in about 30% of patients. This drug helps improve survival rates in patients with HER2 positive metastatic breast cancer when it is used in combination with paclitaxel.
 * <span style="font-size: 13.5pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Side Effects of Chemotherapy **
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting. Aprepitant (Emend), a new drug for preventing chemotherapy-caused nausea and vomiting, was approved in 2006.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Diarrhea
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Temporary hair loss
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Weight loss
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Fatigue
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Depression
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Anemia. The erythropoietins epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) stimulate red blood cell production and can help reduce or prevent anemia, resulting in significant improvement in quality of life. Aranesp persists longer in the blood than epoetin alfa and may therefore require fewer injections.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">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.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Liver and kidney damage.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Abnormal blood clotting (//thrombocytopenia//).
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Allergic reaction, particularly to platinum-based drugs.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">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.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Sexual dysfunction.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Rarely, secondary cancers such as leukemia.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Between a quarter and a third of women report problems in concentration, motor function, and memory, which can be long-term. In one study, women were experiencing such symptoms 2 years after treatment, although by 4 years they had resolved.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">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.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">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.

Radiation therapy — also called radiotherapy — is a highly targeted, highly effective way to destroy cancer cells in the breast that may stick around after surgery. Radiation can reduce the risk of breast cancer recurrence by about 70%. Despite what many people fear, radiation therapy is relatively easy to tolerate and its side effects are limited to the treated area. Your radiation treatments will be overseen by a radiation oncologist, a cancer doctor who specializes in radiation therapy. In this section you can learn more about radiation therapy, including: <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';"> <span style="display: none; font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman'; mso-hide: all;"> **Radiation Therapy**
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|How Radiation Works] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|When is Radiation Appropriate?] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|Types of Radiation] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|External Radiation: What to Expect] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|Internal Radiation: What to Expect] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|Managing Skin Side Effects] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|Managing Other Side Effects of Radiation] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|Radiation for Metastatic Breast Cancer] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|Ten Key Points About Radiation Therapy] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">
 * <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|Staying on Track with Radiation Therapy] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">

There are 2 main ways in which radiation therapy can be given. External beam radiation This is the most common type of radiation therapy for women with breast cancer. The radiation is focused from a machine outside the body on the area affected by the cancer. The extent of radiation depends on whether a lumpectomy or mastectomy was done and whether or not lymph nodes are involved. If a lumpectomy was done, the entire breast receives radiation, and an extra boost of radiation is given to the area in the breast where the cancer was removed to prevent it from coming back in that area. Depending on the size and extent of the cancer, radiation may include the chest wall and underarm area as well. In some cases, the area treated may also include supraclavicular lymph nodes (nodes above the collarbone) and internal mammary lymph nodes (nodes beneath the breast bone in the center of the chest). When given after surgery, external radiation therapy is usually not started until the tissues have been able to heal for about a month. If chemotherapy is to be given as well, radiation therapy is usually delayed until chemotherapy is complete. Before your treatments start, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. They will make some ink marks or small tattoos on your skin that they will use later as a guide to focus the radiation on the right area. You may want to talk to your health care team to find out if these marks will be permanent. Lotions, powders, deodorants, and antiperspirants can interfere with external beam radiation therapy, so your health care team may tell you not to use them until treatments are complete. External radiation therapy is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time -- getting you into place for treatment -- usually takes longer. The most common way breast radiation is given is 5 days a week (Monday thru Friday) for about 6 to 7 weeks. Newer approaches now being studied involve giving radiation over an even shorter period of time. In one approach, larger doses of radiation are given each day, but the course of radiation is shortened to only 5 days. In another approach, known as //intraoperative radiation therapy// (IORT), a single large dose of radiation is given in the operating room right after lumpectomy (before the breast incision is closed). Other forms of accelerated radiation are described below in the section on brachytherapy. It is hoped that these newer approaches may prove to be at least equal to the current, standard breast irradiation, but many doctors still consider them to be experimental at this time. Women who are interested in these approaches may want to ask their doctor about taking part in clinical trials of accelerated breast irradiation now going on. In some women, the breast becomes smaller and firmer after radiation therapy. Having radiation may also affect a woman's chances to have breast reconstruction. Radiation therapy of axillary lymph nodes also can cause lymphedema (see the section, " <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|What will happen after treatment for breast cancer?] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">"). In rare cases, radiation therapy may weaken the ribs, which could lead to a fracture. In the past, parts of the lungs and heart were more likely to get some radiation, which could lead to long-term damage of these organs in some women. Modern radiation therapy equipment allows doctors to better focus the radiation beams, so these problems are rare today. A very rare complication of radiation to the breast is the development of another cancer called angiosarcoma (see " <span style="font-size: 12pt; color: blue; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">[|What is breast cancer?] <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">"). These rare cancers can grow and spread quickly. Brachytherapy Brachytherapy, also known as //internal radiation//, is another way to deliver radiation therapy. Instead of aiming radiation beams from outside the body, radioactive seeds or pellets are placed directly into the breast tissue next to the cancer. It is often used as a way to add an extra boost of radiation to the tumor site (along with external radiation to the whole breast), although it may also be used by itself (see below). Tumor size, location, and other factors may limit who can get brachytherapy. There are different types of brachytherapy. Intracavitary brachytherapy (MammoSite®): This method of brachytherapy consists of a small balloon attached to a thin tube. The deflated balloon is inserted into the space left by the lumpectomy and is filled with a salt water solution. (This can be done at the time of lumpectomy or within several weeks afterward.) The balloon and tube are left in place throughout treatment (with the end of the tube sticking out of the breast). Twice a day a source of radioactivity is placed into the middle of the balloon through the tube and then removed. This is done for 5 days as an outpatient treatment. The balloon is then deflated and removed. While these methods are sometimes used as ways to add a boost of radiation to the tumor site (along with external radiation to the whole breast), they are also being studied in clinical trials as the only source of radiation for women who have had a lumpectomy. In this sense they can also be considered forms of //accelerated partial breast irradiation//. Early results have been promising, but long-term results are not yet available, and it's not yet clear if irradiating only the area around the cancer will reduce the chances of the cancer coming back as much as giving radiation to the whole breast. The results of studies now being done will probably be needed before more doctors recommend accelerated partial breast irradiation as a standard treatment option. ||
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Radiation therapy is treatment with high-energy rays or particles that destroy cancer cells. This treatment may be used to kill any cancer cells that remain in the breast, chest wall, or underarm area after breast-conserving surgery. Radiation may also be needed after mastectomy in cases with either a cancer larger than 5 cm in size, or when cancer is found in the lymph nodes.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Accelerated breast irradiation: **<span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">The standard approach of giving external radiation for 5 day a week over many weeks can be inconvenient for many women. Some doctors are now using other schedules, such as giving slightly larger daily doses over only 3 weeks, which seems to work about as well.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Possible side effects of external radiation: **<span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';"> The main short-term side effects of external beam radiation therapy are swelling and heaviness in the breast, sunburn-like skin changes in the treated area, and fatigue. Your health care team may advise you to avoid exposing the treated skin to the sun because it may make the skin changes worse. Changes to the breast tissue and skin usually go away in 6 to 12 months.
 * <span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">Interstitial brachytherapy: **<span style="font-size: 12pt; font-family: 'Times New Roman','serif'; mso-fareast-font-family: 'Times New Roman';">In this approach, several small, hollow tubes called catheters are inserted into the breast around the area of the lumpectomy and are left in place for several days. Radioactive pellets are inserted into the catheters for short periods of time each day and then removed. This method of brachytherapy has been around longer (and has more evidence to support it), but it is not used as much anymore.