Chapter 086. Breast Cancer (Part 11)

Chemotherapy Unlike many other epithelial malignancies, breast cancer responds to multiple chemotherapeutic agents, including anthracyclines, alkylating agents, taxanes, and antimetabolites. Multiple combinations of these agents have been found to improve response rates somewhat, but they have had little effect on duration of response or survival. The choice among multidrug combinations frequently depends on whether adjuvant chemotherapy was administered and, if so, what type. While patients treated with adjuvant regimens such as cyclophosphamide, methotrexate, and fluorouracil (CMF regimens) may subsequently respond to the same combination in the metastatic disease setting, most oncologists use drugs to which the patients have not...
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Chapter 086. Breast Cancer (Part 11) Chapter 086. Breast Cancer (Part 11) Chemotherapy Unlike many other epithelial malignancies, breast cancer responds tomultiple chemotherapeutic agents, including anthracyclines, alkylating agents,taxanes, and antimetabolites. Multiple combinations of these agents have beenfound to improve response rates somewhat, but they have had little effect onduration of response or survival. The choice among multidrug combinationsfrequently depends on whether adjuvant chemotherapy was administered and, ifso, what type. While patients treated with adjuvant regimens such ascyclophosphamide, methotrexate, and fluorouracil (CMF regimens) maysubsequently respond to the same combination in the metastatic disease setting,most oncologists use drugs to which the patients have not been previouslyexposed. Once patients have progressed after combination drug therapy, it is mostcommon to treat them with single agents. Given the significant toxicity of mostdrugs, the use of a single effective agent will minimize toxicity by sparing thepatient exposure to drugs that would be of little value. No method to select thedrugs most efficacious for a given patient has been demonstrated to be useful. Most oncologists use either an anthracycline or paclitaxel following failurewith the initial regimen. However, the choice has to be balanced with individualneeds. One randomized study has suggested docetaxel may be superior topaclitaxel. A nanoparticle formulation of paclitaxel (abraxane) has also shownpromise. The use of a humanized antibody to erbB2 [trastuzumab (Herceptin)]combined with paclitaxel can improve response rate and survival for womenwhose metastatic tumors overexpress erbB2. The magnitude of the survivalextension is modest in patients with metastatic disease. Similarly, the use ofbevacizumab (avastin) has improved the response rate and response duration topaclitaxel. Objective responses in previously treated patients may also be seenwith gemcitabine, capecitabine, navelbine, and oral etoposide. High-Dose Chemotherapy Including Autologous Bone MarrowTransplantation Autologous bone marrow transplantation combined with high doses ofsingle agents can produce objective responses even in heavily pretreated patients.However, such responses are rarely durable and do not alter the clinical course formost patients with advanced metastatic disease. Stage III Breast Cancer Between 10 and 25% of patients present with so-called locally advanced, orstage III, breast cancer at diagnosis. Many of these cancers are technicallyoperable, whereas others, particularly cancers with chest wall involvement,inflammatory breast cancers, or cancers with large matted axillary lymph nodes,cannot be managed with surgery initially. Although no randomized trials haveproved the efficacy of neoadjuvant chemotherapy, this approach has gainedwidespread use. More than 90% of patients with locally advanced breast cancershow a partial or better response to multidrug chemotherapy regimens that includean anthracycline. Early administration of this treatment reduces the bulk of thedisease and frequently makes the patient a suitable candidate for salvage surgeryand/or radiation therapy. These patients should be managed in multimodalityclinics to coordinate surgery, radiation therapy, and systemic chemotherapy. Suchapproaches produce long-term disease-free survival in about 30–50% of patients. Breast Cancer Prevention Women who have one breast cancer are at risk of developing a contralateralbreast cancer at a rate of approximately 0.5% per year. When adjuvant tamoxifenis administered to these patients, the rate of development of contralateral breastcancers is reduced. In other tissues of the body, tamoxifen has estrogen-like effectsthat are beneficial: preservation of bone mineral density and long-term lowering ofcholesterol. However, tamoxifen has estrogen-like effects on the uterus, leading toan increased risk of uterine cancer (0.75% incidence after 5 years on tamoxifen).Tamoxifen also increases the risk of cataract formation. The Breast CancerPrevention Trial (BCPT) revealed a >49% reduction in breast cancer among women with a risk of at least 1.66%taking the drug for 5 years. Raloxifene has shown similar breast cancer preventionpotency but may have different effects on bone and heart. The two agents havebeen compared in a prospective randomized prevention trial (the STAR trial). Theagents are approximately equivalent in preventing breast cancer with fewerthromboembolic events and endometrial cancers with raloxifene; however,raloxifene did not reduce noninvasive cancers as effectively as tamoxifen, so noclear winner has emerged. ...