br Conflict of interest br Funding This work
Conflict of interest
Funding This work was supported by the National Institutes of Health MSK Cancer Center Support Grant/Core Grant [P30 CA008748]. The funding source had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Summary of key points
Standardisation of pre-analytical factors
These requirements apply to core biopsies and resections. There are no changes to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2013 HER2 testing guidelines and their 2010 guidelines for the immunohistochemical testing of oestrogen and LIMKi 3 receptors that recommended all biomarker testing be performed on core biopsies of the primary tumour.
Clarification of the IHC 2+ category
Discretionary repeat HER2 testing
The five ASCO/CAP groupings of dual ISH HER2 test results Five clinical scenarios encountered in HER2 evaluation of breast cancers are enumerated. Groups 1 and 5 comprise over 95% of test results. For the 5% of cancers in groups 2–4, strategies for further investigation are proposed, emphasising concurrent IHC, dual probe ISH and second opinions. Final results are categorised per Table 1 and Fig. 1.
Use of alternate chromosome 17 probes or other genetic methods
Footnotes and practice points 1. To what extent does this document apply to practice to the wider Australasian region? 2. Given that core needle biopsies are now recommended as the preferred sample for biomarker evaluation is it now envisaged that BreastScreen will cover the cost of the HER2 testing that will be required on the core biopsies? 3. Very often the core and the resection specimen will be reported by different laboratories. How will the pathologist reporting the resection specimen know whether HER2 testing should be carried out? 4. What is the revised HER2 testing workflow likely to be in the light of these changes? 5. The HER2 equivocal category was specified previously and FISH testing was used for establishing a final result in these cases. How are such cases to be dealt with now? The focus of the 2018 guidelines is to assist in the binary management decisions of whether to administer HER2 targeted therapy or not by offering strategies for resolving equivocal findings. In the uncommon 2–4 subtypes, in the first instance a second opinion from an independent observer is required to confirm the relevant clinical subgroup. If confirmed as belonging to subgroups 2–4, evaluation of the immunohistochemistry can be helpful in establishing the HER2 status of the case for the purposes of patient management. In such cases a finding of 3+ IHC leads to a positive HER2 status. In group 3 cases, either 2+ or 3+ IHC results in a positive result. IHC counts of 0 or 1+ will lead to a negative HER2 status, with the comments recommended by ASCO/CAP and reproduced in Appendix A. 6. What are the specific circumstances where new HER2 testing should be performed after an initial positive HER2 result? These circumstances include histological grade 1 carcinoma of the following types: 7. Under which specific circumstances should a new HER2 test on the resection specimen be considered after a negative HER2 result on a core needle biopsy? These include:
Acknowledgements CanSAC and Prof S. O'Toole for their valuable feedback. Ms Meagan Judge for support with project management. The editors and anonymous reviewers of Pathology for their helpful suggestions that have assisted in the presentation of this work.
Introduction The human epidermal growth factor receptor (EGFR) 2 (HER2) is a receptor tyrosine kinase, belonging to the EGFR group . It is over-expressed in breast cancer especially the ductal carcinoma with poor prognosis . The human HER2 molecule is of 84% amino acid sequence homology to the rat neu protein of rat neuroblastoma , . The humanized anti-HER2 antibody trastuzumab (Herceptin) is effective in treating HER2-positive breast cancer showing an objective response rate of 12–34% . However, patients often develop resistance against trastuzumab , , possibly due to the compensatory activities via alternative signaling pathways , . It has also been reported that a risk of cardiac toxicity ,  limits the clinical use of trastuzumab , , warranting the search for other active therapies .