Breast cancer
Description
An in-depth report on the causes, diagnosis, treatment, and prevention of breast cancer.
Alternative Names
Mammograms; Mastectomy
Chemotherapy
Chemotherapy regimens are designed to kill cancer cells throughout the body. It has advantages for nearly every patient regardless of whether the cancer is hormone receptor-positive or negative.
Adjuvant and Neoadjuvant Regimens
Adjuvant chemotherapy is used after surgery, radiation, or both. Its goal is to eradicate microscopic disease in other parts of the body. Neoadjuvant chemotherapy, which is given before other treatments, is also proving to be useful for women with locally advanced breast cancer (Stage III). In such cases, it may reduce the tumor size so that it is operable.
Candidates for Adjuvant Chemotherapy.
Chemotherapy after surgery (adjuvant chemotherapy) is an appropriate consideration for most women with invasive breast cancer, regardless of menopausal status. Studies report that adjuvant therapy may also benefit women with early-stage cancers. 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, and whether the cancer is hormone receptor-positive or -negative.
A 2006 study in the
Journal of the American Medical Association
indicated that 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. Adjuvant hormonal therapy is also an important treatment for women with hormone receptor-positive cancer.
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:
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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.
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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.
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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).
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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.
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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
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:
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Cyclophosphamide, 5-fluorouracil (5-FU), and methotrexate (CMF) with a corticosteroid (such as prednisone).
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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.
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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.
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 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:
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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.
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Diarrhea
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Temporary hair loss
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Weight loss
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Fatigue
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Depression
Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. They include the following:
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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.
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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.
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Liver and kidney damage.
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Abnormal blood clotting (
thrombocytopenia
).
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Allergic reaction, particularly to platinum-based drugs.
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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.
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Sexual dysfunction.
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Rarely, secondary cancers such as leukemia.
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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.
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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.
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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 high-dose therapy for treatment of high risk breast cancer, this approach can no longer be generally recommended and should not be used outside of a clinical trial setting. The results of several randomized studies have failed to show a convincing advantage for the use of high-dose therapy. Nevertheless, some experts believe this approach can still be useful in selected patients, and studies continue. In general, however, transplantation has a limited role in breast cancer management, and its use should be restricted to clinical trials.
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Review Date: 4/3/2007
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Reviewed By: Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, M.D., Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (10/2/2006).
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