Bright-field In Situ Hybridization for HER2 Gene Amplification in Breast Cancer Using Tissue Microarrays Correlation Between Chromogenic (CISH) and Automated Silver-enhanced (SISH) Methods With Patient Outcome

Introduction: HER2 gene amplification or overexpression occurs in 15% to 25% of breast cancers and has implications for treatment and prognosis. The most commonly used methods for HER2 testing are fluorescence in situ hybridization (FISH) and immunohistochemistry. FISH is considered to be the reference standard and more accurately predicts response to trastuzumab, but is technically demanding, expensive, and requires specialized equipment. In situ hybridization is required to be eligible for adjuvant treatment with trastuzumab in Australia. Bright-field in situ hybridization is an alternative to FISH and uses a combination of in situ methodology and a peroxidase-mediated chromogenic substrate such as diaminobenzidine [chromogenic in situ hybridization (CISH)] or multimer technology coupled with enzyme metallography [silver-enhanced in situ hybridization (SISH)] to create a marker visible under bright-field microscopy. CISH was introduced into diagnostic testing in Australia in October 2006. SISH methodology is a more recent introduction into the testing repertoire. An evaluation of CISH and SISH performance to assess patient outcome were performed using tissue microarrays. Materials and Methods: Tissue microarrays were constructed in duplicate using material from 593 patients with invasive breast carcinoma and assessed using CISH and SISH. Gene amplification was assessed using the American Society of Clinical Oncology/College of American Pathologists guideline and Australian HER2 Advisory Board criteria (single probe: diploid, 1 to 2.5 copies/nucleus; polysomy >2.5 to 4 copies/nucleus; equivocal, >4 to 6 copies/nucleus; low-level amplification, >6 to 10 copies/nucleus and high-level amplification >10 copies/nucleus; dual probe HER2/CHR17 ratio: nonamplified 2.2). Results: Results were informative for 337 tissue cores comprising 230 patient samples. Concordance rates were 96% for HER2 single probe CISH and SISH and 95.5% for single probe CISH and dual probe HER2/CHR17 SISH. Both bright-field methods correlated with immunohistochemistry results and with breast cancer-specific survival. Conclusions: HER2 SISH testing combines the advantages of automation and bright-field microscopy to facilitate workflow within the laboratory, improves turnaround time, and correlates with patient outcome

The effect of adjuvant chemotherapy on cognitive functioning in early breast cancer: Implications for outcomes research and oncology practice

Outcomes research is an important focus of public and research policy in Australia. Recent reports of cognitive impairment after chemotherapy for breast cancer have highlighted the emerging importance of cognition as a clinically relevant outcome. To date, most studies have utilised cross-sectional study designs to investigate impairment after treatment. Future research requires a within-group study design that utilises a longitudinal repeated measures approach to identify the nature and magnitude of cognitive change after adjuvant chemotherapy and to evaluate factors that mediate cognitive functioning. The results of within-group studies will also provide the foundations for individual patient assessment, with its focus on the development of tailored behavioural interventions for significantly impaired patients. As cognitive research matures, the neuropsychologist will become an important addition to the multidisciplinary cancer care team