Annals of oncology : official journal of the European Society for Medical Oncology
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Following the pivotal clinical trials of trastuzumab (Herceptin), further phase II and III studies have been initiated. Preliminary results from a phase II, dose-response study of single-agent trastuzumab in 113 HER2-positive metastatic breast cancer patients without prior chemotherapy for stage IV disease have shown that the overall response rate was 23% (six complete responses and 20 partial responses), with similar results using both standard- and high-dose regimens of trastuzumab. Another phase II study of trastuzumab plus paclitaxel, both given weekly, in 63 HER2-positive and -negative patients with metastatic breast cancer produced an overall response rate of 62% in HER2-positive and 44% in HER2-negative patients. ⋯ These include docetaxel +/- trastuzumab, aromatase inhibitor +/- trastuzumab, CMF (cyclophosphamide, methotrexate, 5-fluorouracil) +/- trastuzumab, vinorelbine + trastuzumab, all in HER2-positive patients, and epirubicin-cyclophosphamide (EC) + trastuzumab in HER2-positive patients vs. EC alone in HER2-negative patients. The results from these trials should be available over the next one to two years.
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Human epidermal growth factor receptors (HER/erbB) constitute a family of four cell surface receptors involved in transmission of signals controlling normal cell growth and differentiation. A range of growth factors serve as ligands, but none is specific for the HER2 receptor. HER receptors exist as both monomers and dimers, either homo- or heterodimers. ⋯ This explains why HER2 overexpression is an indicator of poor prognosis in breast tumors and may be predictive of response to treatment. HER2 is a highly specific and promising target for new breast cancer treatments. The recombinant human anti-HER2 monoclonal antibody (rhuMAb-HER2, trastuzumab, Herceptin) induces rapid removal of HER2 from the cell surface, thereby reducing its availability to heterodimers and reducing oncogenicity.
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Minimal criteria for the diagnosis of multiple myeloma are provided. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, primary systemic amyloidosis and metastatic carcinoma must be included in the differential diagnosis. Patients with multiple myeloma should not be treated unless they have an increasing M-protein in the serum or urine, development of anemia, hypercalcemia, renal insufficiency, lytic lesions, fractures or extra-medullary plasmacytomas. ⋯ If the patient is younger than 70 years, the physician should consider the possibility of an autologous peripheral blood stem-cell transplant. Ideally, this should be done as part of a prospective study. Hematopoietic stem cells are damaged by alkylating agents so they must be collected before these agents are given. Autologous stem-cell transplantation does not produce a cure and most patients will relapse. The appropriate timing of an autologous stem-cell transplant has not been ascertained. Hopefully, better preparative regimens and the removal of contaminated tumor cells from the peripheral blood will make an autologous transplant more effective. Another major question is whether double (tandem) transplants are superior to a single autologous stem-cell transplant. A current French Myeloma Group Study randomized study should answer this question. Allogeneic transplantation for multiple myeloma must be made safer because the transplant-related mortality is 40%. The relapse of multiple myeloma following allogeneic transplant is a major problem and consequently the preparative regimens must be improved. The infusion of donor lymphocytes following relapse after an allogeneic transplant is useful. New approaches with immunologic aspects including the use of dendritic cells and vaccines are of potential importance for the future.
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Review Case Reports
Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: case report and review of the literature.
Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.