Treatment of Breast Cancer
Surgery and radiation therapy are considered local treatments. They focus on ridding a limited or local area--such as the breast, chest wall, and axillary nodes--of the cancer. Chemotherapy, hormone therapy, supplementation, and diet modification are considered systemic therapy. In systemic therapy, the entire body is treated in order to eradicate any cancer cells that may have spread from the breast tumor to other areas of the body. A woman's treatment depends on many factors, such as age, tumor stage, and estrogen-receptor status. However, deciding on a particular treatment is both a personal and a medical choice. Each treatment option has risks and benefits. Therefore, the type of treatment a woman chooses should be based on an understanding of how these risks and benefits relate to one's personal values and lifestyle. Local Treatment
Breast cancer surgery strives to completely remove the tumor from the breast. However, surgery may also include the removal of one, some, or all of the axillary lymph nodes. Following surgery, both the tumor and/or lymph nodes are sent to a pathologist for examination to determine the stage of the breast cancer so the physician and patient can decide what additional treatment may be required after surgery. There are two basic types of surgery for breast cancer: breast-conserving surgery and total mastectomy. Breast-Conserving Surgery Breast-conserving surgery consists of the removal of the breast tumor and some surrounding normal tissue. This procedure can be referred to as a lumpectomy, wide excision, or partial-radical mastectomy. During the operation, axillary lymph nodes may also be removed. During breast-conserving surgery, the patient is usually given general anesthetic, causing unconsciousness. The surgeon then opens the breast and removes the tumor and a small amount of normal tissue. The surgeon then sutures together the edges of the incision, trying to keep the breast as normal-looking as possible. If axillary lymph nodes are removed, the surgeon will also open the area under the armpit on the same side as the affected breast, removing about 10-15 lymph nodes. However, if a sentinel node biopsy is performed only 1-3 lymph nodes are removed and used to assess node status. Breast-conserving surgery can be done on palpable tumors (tumors that the physician is able to feel), as well as tumors that are not palpable but that can be located by mammography. In the case of tumors that are not palpable, a radiologist will insert a very thin wire into the area of the tumor in the breast during a mammogram. (This procedure is called wire-localization or needle-localization and was discussed earlier.) The wire remains in the breast until the surgery and serves as a guide for the surgeon. The tumor and lymph nodes removed during surgery are sent to a pathologist, who will assess the tumor margins to determine whether there is an adequate amount of normal tissue surrounding the tumor. This margin of normal tissue helps indicate whether or not the entire tumor was removed. If clean, uninvolved, or negative margins are found, this indicates that only normal tissue remains at the edges of the tissue removed and no additional surgery is needed. If normal tissue does not completely surround the tumor, the margins are considered "dirty," "involved," or "positive." Additional surgery will then be done to obtain adequate margins (Love et al. 1997). A second breast-conserving operation is usually done if the tumor margins are found to be "dirty." This surgery is called a re-excision. If it does not achieve negative margins, a total mastectomy may be recommended. Total Mastectomy A total mastectomy procedure entails the removal of the entire breast. This may include an axillary dissection as well. For women who have decided to have breast reconstruction, this procedure will directly follow the mastectomy surgery. A total mastectomy is done under general anesthetic. During the operation, all of the breast tissue is removed, including the nipple. For women considering breast reconstruction during or sometime after surgery, as much skin as possible is left intact in order to cover the implant. If a woman is not having reconstruction or is having it at a later time, the skin in the area is sewn together and a drainage tube is inserted so fluid from the healing wound can drain away. The pathologist will evaluate the breast tissue and lymph nodes. The results of these tests will help determine which adjuvant therapy will be used. Luteal Phase Surgery Studies have suggested that premenopausal women who have their breast-conserving procedure or mastectomy done during the later part of their menstrual cycle (during the luteal phase) may have a better outcome after surgery. However, researchers are still assessing the benefits to "timing surgery" (Senie et al. 1997; NCI 1998). Radiation Therapy Radiation therapy (also known as radiotherapy) is considered a local treatment for breast cancer that uses targeted, high-energy x-rays to impede cancer cells' ability to grow and divide. The aim of radiation therapy is to rid the breast, chest, and axillary lymph nodes of cancer by using high-energy x-rays. For women with early-stage breast cancer, radiation therapy is most often performed following breast-conserving surgery. It is believed that after conserving surgery, there may still be undetectable microscopic cancer in the breast. Therefore, to reduce the chance of recurrence, radiation therapy is necessary to try to eliminate any cancer that might have been missed. Radiation therapy may also be used on the axillary lymph nodes and the chest wall following total mastectomy. Radiation therapy usually commences several weeks after surgery. However, it may be postponed if a patient is receiving chemotherapy first. Adjuvant Treatment
Several types of systemic treatments are used for early-stage breast cancer: chemotherapy, hormone therapy, supplementation, and diet modification. These therapies are referred to as adjuvant, meaning "in addition to," because they are used with surgery and radiation. Except for some women with very small tumors (less than 1 cm) and with lymph nodes that do not have cancer, adjuvant therapy is usually recommended for women with early-stage breast cancer. Which therapies, and in what combination, depends on many things, such as the woman's age, whether the tumor has estrogen receptors (discussed below), and the number of positive lymph nodes. Chemotherapy Chemotherapy uses drugs that can be taken in pill form or injected intravenously to kill cancer cells. Sometimes, a combination of the two is used. However, intravenous drugs must be given in a hospital or doctor's office. Depending on the drugs used, chemotherapy is administered once or twice a month for 3-6 months. Sometimes the range might be extended to 7 or 8 months. Chemotherapy usually begins 4-6 weeks after the final surgery and is administered in a combination of 2-3 drugs that have been found to be the most effective. Although the exact schedule depends on the specific drugs used, drugs may be given on day 1 of a 3-week cycle or there may be a period of a week or two on the drugs, followed by a period of about 2 weeks off the drugs. The conventional belief among oncologists is that this cycling allows the body a chance to rest and recover between treatments. Critics argue that this also gives the cancer cells an opportunity to rest, recover, and possibly mutate into a type of cancer that is chemotherapy-resistant. An entire course of chemotherapy lasts about 4-6 months, again depending on the drugs used. Unfortunately, these drugs have many side effects that can damage or destroy healthy tissues throughout the body. Research indicates that allowing the body a chance to rest and recover may also allow the cancer a chance to rest, recover, and possibly mutate into a type of cancer that is chemotherapy resistant. Recent studies indicate that a more scientific approach would be to lower the dose of conventional cytotoxic agents, reschedule their application, and combine chemotherapy drugs with agents designed to interfere with cancer's ability to produce new blood vessels (angiogenesis) (Holland et al. 2000). This lower-dose approach, known as "metronomic dosing," uses a dosing schedule as often as every day. An amount as low as 25% of the maximum tolerated dose (MTD) in combination with antiangiogenesis agents targets the endothelial cells making up the blood vessels and microvessels feeding the tumor. Endothelial cells can be killed with much less chemotherapy than cancer cells, and the side effects to healthy tissue and the patient in general are dramatically reduced (Hanahan et al. 2000). Hormone Therapy
Hormone receptor-positive tumors can consist of cancer cells with receptor sites for estrogen, progesterone, or both. The hormones attach to receptor sites and promote cell proliferation. Hormone therapy blocks the hormones from attaching to the tumor receptor sites and may slow or stop the cancer's growth. The drug most often used in this type of endocrine therapy is tamoxifen, with a response rate from 30-60%. Other therapies are sometimes used, such as aromatase inhibitors (that inhibit the conversion of precursors to estrogens) or oophorectomy (the removal of the ovaries). Tamoxifen (Nolvadex) Tamoxifen is an antiestrogenic drug used only in women whose tumors are estrogen or progesterone receptor-positive. This endocrine therapy blocks the female hormone estrogen from binding to the tumor cells. Tamoxifen has been a gold standard hormonal agent used for the treatment of breast cancer for more than 20 years. It is a prototype for a class of compounds called selective estrogen receptor-modulators (SERMs) of breast cancer but is also an effective primary treatment for advanced disease. Women with early-stage breast cancer who take tamoxifen have, on average, a 25% proportional increase in their chances of surviving 5 years after diagnosis. According to data presented in 1999 at the 22nd Annual San Antonio Breast Cancer Symposium, tamoxifen does not work equally well in all women. As the name implies, estrogen receptor-negative tumors do not have estrogen receptors, or have very few, and therefore do not respond to tamoxifen. The specific aim of a Phase III study of 2691 high-risk cancer patients was to test the effectiveness of tamoxifen with both pre- and postmenopausal subsets of receptor-negative and receptor-positive tumors. The study concluded that both 5-year disease-free and overall survival with the addition of tamoxifen to chemotherapy in patients with receptor-positive tumors was significantly higher than with chemotherapy alone, while no such advantage in disease-free or overall survival was found in receptor-negative patients. Further, in the receptor-positive postmenopausal group, the addition of tamoxifen showed a significant improvement in both disease-free and overall survival. However, in the premenopausal receptor-negative patients, tamoxifen led to a worse outcome, as indicated by the significantly reduced survival rate (ONI 2000). Women with estrogen receptor-negative tumors may receive chemotherapy instead of tamoxifen. Therefore, for the patient whose breast cancer's growth is estrogen-dependent, tamoxifen can keep estrogen from these cells, slowing or stopping their growth. Tamoxifen is a pill taken daily for 5 years. To date, studies do not show any benefit to taking tamoxifen for longer than 5 years (NCI 1998). Studies show that the use of tamoxifen as a postsurgical adjuvant therapy can reduce the chances of the cancer reoccurring. Tamoxifen has a host of side effects, including hot flashes, weight gain, mood swings, abnormal secretions from the vagina, fatigue, nausea, depression, loss of libido, headache, swelling of the limbs, decreased number of platelets, vaginal bleeding, blood clots in the large veins (deep venous thrombosis), blood clots in the lungs (pulmonary emboli), cataracts (Fisher et al. 1998), and--the side effect of the greatest concern--endometrial cancer (Harris et al. 1997). Studies have shown an increase of early-stage endometrial cancer (cancer of the lining of the uterus) among women taking tamoxifen, and the risk increases if the drug is taken for more than 5 years. Endometrial cancer is usually diagnosed at a very early stage and is usually curable by surgery. The studies have also shown an increased risk of uterine sarcoma (a rare cancer of the connective tissues of the uterus) among women taking tamoxifen. Unusual vaginal bleeding is a common symptom of both of these cancers. The treating physician should be notified immediately if vaginal bleeding occurs. Raloxifene Raloxifene is a drug similar to tamoxifen. It is a selective estrogen receptor-modulator (SERM) that blocks the effect of estrogen on breast tissue and breast cancer. It is currently in the testing phase to assess its effectiveness in reducing the risk of developing breast cancer. Pending testing completion, this drug is not recommended as hormonal therapy for women who have been diagnosed with breast cancer. Toremifene (Fareston) Toremifene (Fareston) is an antiestrogen drug closely related to tamoxifen that may be an option for postmenopausal women with breast cancer that has metastasized. Fareston is a type of antiestrogen medication that is used in tumors that are estrogen-receptor-positive or estrogen receptor-unknown. Some patients treated with antiestrogens who have bone metastasis may experience a tumor flare with pain and inflammation in the muscles and bones that will usually subside quickly. Blood calcium level should be monitored because tumor flare can cause a raised level of calcium in the blood (hypercalcemia) with symptoms of nausea, vomiting, and thirst. Often a short stay in the hospital is necessary until the calcium levels have been reduced or treatment may need to be stopped. Fareston is being studied in clinical trials for use in earlier stages of breast cancer. Anastrozole (Arimidex), Femara (Letrozole), and Aromasin (Exemestane) Anastrozole (Arimidex), Femara (Letrozole), and Aromasin (exemestane) are three hormonal therapy drugs referred to as aromatase inhibitors. Aromatase is the enzyme that actually converts male hormones into female hormones in postmenopausal women. Premenopausal women get most of their estrogen from the ovaries. But postmenopausal women still have estrogen in their bodies, and it is this conversion of androgens coming from other glands in the body to estrogen that needs to be interrupted so the breast cancer cells no longer have estrogen to stimulate their growth. Unlike tamoxifen, which slows the growth of breast cancer by preventing estrogen from activating its receptor, anastrozole blocks an enzyme needed for the production of estrogen, inhibiting the conversion of precursors to estrogens, and is effective in hormone receptor-positive breast cancers. Anastrozole is currently an option for women whose advanced breast cancer continues to grow during or after tamoxifen treatment. Studies are ongoing to compare tamoxifen and anastrozole as adjuvant hormonal therapies. The initial results in a large-scale clinical study were announced at the 24th Annual San Antonio Breast Cancer Symposium. The study results indicated that anastrozole (Arimidex) was better than tamoxifen at preventing the recurrence of breast cancer. The study was conducted in 381 centers in 21 countries, involved 9366 patients, and examined three treatment arms: tamoxifen alone, tamoxifen in combination with other therapy, and anastrozole alone. The trial results showed that women taking anastrozole experienced fewer side effects than women taking tamoxifen. However, women taking tamoxifen experienced fewer musculoskeletal disorders. The study was only conducted for a relatively short period of time, 2 years, and the long-term effects (5 years and beyond) are not yet known. Longer-term studies are needed to assess both the benefits and risks of this therapy. However, most recent studies have showed anastrozole to be slightly superior to tamoxifen (Susman 2001). Possible side effects of aromatase-inhibitor drugs include those associated with menopausal-like estrogen deficiency, such as hot flashes, night sweats, menstrual irregularity, depression, bone or tumor pain, pulmonary embolism (a blood clot in the lung), musculoskeletal disorders, and generalized weakness. Megestrol Acetate Megestrol acetate (Megace) is another drug used for hormonal treatment of advanced breast cancer, usually for women whose cancers do not respond to tamoxifen or have stopped responding to tamoxifen. Megestrol acetate is a man-made substance called progestin that is similar to the female hormone progesterone. As with other therapies, there are reported side effects, including an increase in appetite causing weight gain, fluid retention causing ankle swelling, and nausea at the onset of therapy (the nausea usually subsides). In rare cases, allergic reactions, jaundice, and raised blood pressure have been reported. Trastuzumab (Herceptin Genentech) Trastuzumab (Herceptin Genentech) is an antineoplastic drug therapy for women with HER2-positive metastatic breast cancer. This monoclonal antibody therapy differs from traditional treatments, such as chemotherapy and hormone-blocking therapy. Herceptin works by specifically targeting tumor cells that overexpress the HER2 protein. A monoclonal antibody blocks the receptors and prevents activation of genes that induce cell division, thereby slowing the growth of the tumor. The reported side effects are chills, diarrhea, nausea, weakness, headache, and vomiting and possibly damage of the heart muscle, anemia, and nerve pain. Trastuzumab can be used alone or in combination with the drug paclitaxel (Taxol) and is prescribed for metastatic breast cancer. Paclitaxel (Taxol) Paclitaxel (Taxol) belongs to the group of medicines called antineoplastics that interfere with the growth of cancer cells and eventually destroy them. Because the growth of normal body cells may also be affected by paclitaxel, side effects can occur. Some side effects may not occur until months or years after the medicine was used. Side effects include neutropenia ( decreased white blood cell count), anemia (decreased red blood cell count), thrombocytopenia (decreased platelet count), increased risk of infection, fatigue, bruising, hemorrhage, rash, itching, redness, hives, facial flushing, chest pain, difficulty breathing, high or low blood pressure, decreased heart rate, lightheadedness, dizziness, increased perspiration, nausea, shortness of breath, headache, numbness or tingling of the hands and/or feet, muscle aches, bone pain, mouth ulcers (sores), alopecia (loss or thinning of scalp and body hair), decreased appetite, diarrhea, nausea, vomiting, skin burns and ulcers, nail changes, hot flashes, and vaginal dryness. Oophorectomy Oophorectomy is surgery in which the ovaries are removed, therefore eliminating the body's main source of estrogen and progesterone. Prior to the advent of antiestrogen drugs, an oophorectomy was commonly used to treat breast cancer for premenopausal women. Occasionally this procedure is still used in premenopausal women. However, chemotherapy drugs can alter the ovaries and reduce estrogen production. Tamoxifen may block any remaining estrogen effect on cancer cells, allowing many women to avoid surgery. Continued . . . |
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