Recommendations for HER2 testing in the UK

Determining the HER2 status of breast carcinomas is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin(R)), which has recently been licensed for the treatment of metastatic disease. This necessitates a test based on archival material. The preferred analyses are immunohistochemistry with fluorescent in situ hybridisation (FISH) as a follow up test for ambiguous results. Guidelines have been developed for standardised, well controlled procedures for the provision of reliable results. A group of three reference laboratories has been established to provide advice, quality assurance, and materials, where needed

Elemental boron doping behavior in silicon molecular beam epitaxy

Boron-doped Si epilayers were grown by molecular beam epitaxy (MBE) using an elemental boron source, at levels up to 2×1020 cm−3, to elucidate profile control and electrical activation over the growth temperature range 450–900 °C. Precipitation and surface segregation effects were observed at doping levels of 2×1020 cm−3 for growth temperatures above 600 °C. At growth temperatures below 600 °C, excellent profile control was achieved with complete electrical activation at concentrations of 2×1020 cm−3, corresponding to the optimal MBE growth conditions for a range of Si/SixGe1−x heterostructures

Dopant Spatial Distributions: Sample Independent Response Function And Maximum Entropy Reconstruction

We demonstrate the use of maximum entropy based deconvolution to reconstruct boron spatial distribution from the secondary ion mass spectrometry (SIMS) depth profiles on a system of variously spaced boron $\delta$-layers grown in silicon. Sample independent response functions are obtained using a new method which reduces the danger of incorporating real sample behaviour in the response. Although the original profiles of different primary ion energies appear quite differently, the reconstructed distributions agree well with each other. The depth resolution in the reconstructed data is increased significantly and segregation of boron at the near surface side of the $\delta$-layers is clearly shown.Comment: 5 two-columne pages, 3 postscript figures, to appear in Phys. Rev. B1

Effects of endocrine therapy on steroid-receptor content of breast cancer.

In order to determine the mechanisms of relapse following response to endocrine therapy, we have measured the oestrogen receptor (RE) content of biopsies of breast cancer in patients receiving various types of endocrine treatment. RE content fell in responding (means of 260.2 to 12 fmol/mg protein) and in nonresponding (means of 155.1 to 31.8 fmol/mg protein) patients who had measurable receptor at the start of treatment. Some of these patients, and a further group of responders to endocrine therapy, were monitored until relapse. Tumour biopsies at the time of relapse showed that 10/14 tumour samples contained significant RE (mean of 86.7 fmol/mg protein; range less than 10-271 fmol/mg protein) after successful endocrine therapy. No relationship could be found between RE content and plasma gonadotrophin or steroid-hormone concentration, but the fall in RE content correlated with reduced numbers of tumour cells in the biopsy. These results indicate that relapse following successful endocrine therapy in breast cancer does not appear to be due to the emergence of RE-negative tumour cells. The fall in RE content during response to endocrine therapy may be due to reduced tumour-cell content of the biopsy

Phase I/II study of the anti-oestrogen zindoxifene (D16726) in the treatment of advanced breast cancer. A Cancer Research Campaign Phase I/II Clinical Trials Committee study.

We report a phase I/II study of the indole derivative, zindoxifene, an anti-oestrogen with intrinsic oestrogenic activity. We have treated 28 women with advanced breast cancer of whom 26 had received prior endocrine therapy. Oral zindoxifene doses ranged from 10 to 100 mg daily; doses were escalated in some patients. Twenty-five patients were assessed for response; the remaining three patients completed less than 3 weeks of treatment. There were no objective responses; disease stabilised in seven patients for up to 5 months and progressed in the remaining 18. Five patients (including three treated with tamoxifen) responded to subsequent endocrine therapy. Nausea, which was dose-limiting, affected half of the patients treated with 80 mg daily. Metabolites of zindoxifene were detectable in serum at all doses used, and sex hormone binding globulin (SHBG) levels showed a strong tendency to rise at the higher doses, indicating that zindoxifene is absorbed and has biological activity. We conclude that zindoxifene in the doses used in this study has only marginal therapeutic activity in the treatment of advanced breast cancer