This approach may give direction to future research aimed at precisely mapping loci altered in DCIS and help in understanding the biologic events associated with tumor progression or recurrence.

Breast cancer is a genetically complex disease. Fluorescence in situ hybridisation can be used to analyse the genetics of breast-cancer progression in interphase cytogenetics. We have analysed the histological distribution of erbB2 and topoll alpha co-amplification in paraffin sections of invasive breast cancer and show that the co-amplified loci share the same histological distribution in the tumour and have a similar nuclear distribution within individual nuclei. Regions of the tumours without amplification are easily recognized and tumours with erbB2 and topoll alpha co-amplification can be distinguished from those with erbB2 amplification alone. In addition, FISH was used to show polysomy of chromosome 17 in non-invasive ductal carcinoma in situ of the breast and erbB2 amplification in both the invasive and non-invasive components of a breast cancer biopsy. This report of an interphase cytogenetic analysis of non-invasive breast carcinoma in situ demonstrates the usefulness of FISH for the genetic study of breast cancer progression.

#3002 Introduction: Aberrations of chromosome 17 (aneusomy) are common in breast cancer and therefore have a critical impact on the assessment and reporting of HER2 gene amplification in a significant sub-set of cases. There is an ongoing debate as to the proportion of cases for which assessment of chromosome 17 copy number may be important. According to current guidelines1,2, amplification of HER2 is considered to be a HER2/chromosome 17 ratio ≥2.0 and a ratio <2.0 is regarded as non-amplified. For HER2 gene copy number assays, it has been assumed that copy numbers of >6.0 reflect amplification and a result of <4.0 HER2 gene copies per nucleus is always associated with lack of amplification; cases with 4-6 copies per cell are thought to require validation by testing of a parallel section for chromosome 171,2. To our knowledge, this assumption has not been verified experimentally.
 Methods: HER2 and chromosome 17 were measured by dual color FISH in 1711 breast cancer samples referred to the authors laboratories between 2000-2008. Using HER2 copy number and chromosome 17 data the impact of chromosome 17 testing upon accuracy of diagnosis of gene amplification was assessed.
 Results: At a HER2 copy number of 2 to <3, 16 of 488 cases (3.3%) had HER2 amplification; and at a copy number of 3 to <4, 32 of 195 cases (16.4%) were amplified. The proportion of cases with HER2 amplification increased considerably at HER2 copy numbers of 4 to <7: 50.0% at 4 to <5; 67.5% at 5 to <6, and 77.3% at 6 to <7. Virtually all cases were amplified at HER2 copy numbers of ≥7.
 Conclusion: Werecommend that all cases with observed HER2 copy numbers of 2 to 7 should also be analyzed for chromosome 17 in order to accurately determine HER2 gene amplification. This would require analysis of chromosome 17 in 48.3% of all breast cancer cases based upon the study population. Current guidelines1,2 recommend chromosome 17 measurement only in cases with a HER2 copy number of 4 to <6, which represents only 6.6% of all breast cancer cases in the current study. Although single color ISH is becoming more widely used with the availability of CISH, the importance of chromosome 17 measurement cannot be ignored. It is essential that HER2 testing is of high quality, so that optimal patient management can be provided.
 1. Ellis IO, Bartlett J, Dowsett M et al: Updated recommendations for HER2 testing in the UK. J.Clin.Path. 57(3), 233-237 (2004).
 2. Wolff AC, Hammond ME, Schwartz JN et al: American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Journal of Clinical Oncology 25(1), 118-145 (2007). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3002.

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Introduction: The introduction of neo-adjuvant herceptin has led to pathological complete response rates of up to 60% in patients with breast cancer. The traditional (NSABP) definition of pathological complete response includes cases demonstrating residual DCIS and little is known about the effects of neo-adjuvant herceptin in this situation. Current evidence suggests that DCIS is chemo-resistant, but it has also been shown that DCIS is more likely to be HER-2 positive than primary cancer. Results: We describe six patients who received neo-adjuvant chemotherapy and herceptin for biopsy-proven, node-positive, large breast cancers either with an extensive component of concomitant DCIS or a separate DCIS focus. Neo-adjuvant treatment did not result in any changes in the pattern of mammographic calcification seen pre-operatively (Figure 1 a-c), however histopathology of all six specimens showed ductal spaces containing macrophages and calcification but no residual lining epithelium, features consistent with pathological complete response of the DCIS component (Figure 1d). Figure 1: Pathologically complete response of DCIS after neo-adjuvant treatment with herceptin. (a) Pre-treatment mammogram (b) Post neo-adjuvant chemotherapy and herceptin mammogram showing resolution of the mass effect of the primary cancer and unchanged residual mammographic calcification associated with the extensive DCIS component (c) Wire-localised specimen demonstrating excision of calcification (d) Histopathology of the same specimen showing calcium-filled ducts and no residual lining epithelium. Discussion: In conclusion, neo-adjuvant herceptin is associated with complete pathological response of both breast cancer and DCIS. The presence of unchanged persistent mammographic calcification in known regions of DCIS after treatment complicates any role of mammographic surveillance in this group and raises the question of optimal surgical management in the future management of these individuals. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-05.