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- Andersson, J, et al.
(author)
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A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin (R)) on a named patient basis in Sweden
- 2002
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:3, s. 276-281
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Journal article (peer-reviewed)abstract
- Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p=0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines.
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- Andersson, J., et al.
(author)
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Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF
- 2005
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In: Ann Oncol. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 16:5, s. 743-8
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Journal article (peer-reviewed)abstract
- BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.
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- Linderholm, BK, et al.
(author)
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The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer
- 2001
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 61:5, s. 2256-2260
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Journal article (peer-reviewed)abstract
- Wild-type p53 protein has been shown to inhibit angiogenesis through thrombospondin in thepreclinical setting, Here, we determined the associations between the expression of the angiogenic factorvascular endothelial growth factor (VEGF) and the p53 status, including different mutation sites and types,in primary breast cancer. Cytosols from 224 primary breast cancer patients were analyzed with an enzyme immunoassay for determination of human VEGF(165) protein content. p53 status was determined hv cDNA-based sequencing of the entire coding region, by immunohistochemistry (IHC). and by a p53luminometric immunoassay (I,IA) method. Statistically significant associations was found between higher VEGF content and non-wild-type p53 status for all methods; sequence-based data (P = 0.0019), IHC data (P = 0.0068), and the I,IA method (r = 0.427: P > 0.001), Highest VEGF values were detected in tumorswith p53 insertions, deletions, and stop codon mutations (P = 0.0043). Combining p53 status and VEGF content resulted in additional prognostic information, relapse-free survival (RFS: P = 0.0377), overall survival (OS; P = 0.0319), and breast cancer corrected survival (BCCS: P = 0.0292). In multivariate analysis, the relative hazard increased when the VEGF data were added to the p53 status, with a relative hazard of 1.7 for RFS and 3.0 for BCCS, compared with 1.1 fur RFS and 1.4 for BCCS among the patientswith either high VEGF content or p53 mutation. Higher VEGF content was statistically significantly correlated with a worse outcome fur patients with estrogen receptor-positive tumors receiving adjuvant tamoxifen: RFS (P = 0.0471), OS (P = 0.0134), BCCS (P = 0.0064), as well as in multivariate analysis withpoint estimates of 3.4 and 2.1 fur BCCS and RFS, respectively, VEGF expression is related to p53 statusin human breast cancer patients. Combining VEGF with p53 status resulted in better prognostic prediction.
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