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This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.

Summary Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti-human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (X2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (X2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53 mutations could be a late event in this non-familial form of breast cancer.

Background/Aims: Incorporating gene expression profiling into routine clinical practices is beginning to be recommended as part of breast cancer treatment. The aim of the present study was to investigate the decision-making involved in genomic testing from the perspective of patients enrolled in a genomics-based clinical trial of adjuvant chemotherapy. Methods: The prospective SA02 clinical trial was designed to assess the clinical benefits of a genomic test on axillary lymph node-positive (N+) early breast cancer patients. The patients enrolled in the SA02 trial were defined by ‘good prognosis' genomic test results consistent with the delivery of postoperative anthracycline-based chemotherapy without taxane. The present companion study was presented by oncologists to 64 out of the 88 patients enrolled. Data were collected using self-administered questionnaires. Results: The response rate was 67% (questionnaires were returned 35 days on average after enrolment in the trial). Only 33% of the respondents accurately recalled or described their genomic test results. Although most N+ patients classically undergo anthracycline/taxane adjuvant chemotherapy, 23% of the present respondents did not recall participating in the clinical study involving chemotherapy without taxanes. Recall was mainly associated with higher risk perception of chemotherapy-related side effects and better understanding of test results. Among the respondents who recalled participating in the trial, 39% experienced decisional conflicts. Conclusions: Devoting greater efforts to explaining genomic test results to patients could be highly relevant in terms of the trade-off between the risk of unnecessary chemotherapy-related side effects and the loss of survival time possibly resulting from less aggressive treatment.

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