Impact of the 2018 ASCO/CAP guidelines on HER2 fluorescence in situ hybridization interpretation in invasive breast cancers with immunohistochemically equivocal results

Abstract

The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) recently issued updated guidelines on human epidermal growth factor receptor 2 (HER2) testing by fluorescence in situ hybridization (FISH) in invasive breast cancers. In this study, we aimed to investigate the impact of the new recommendations on HER2 FISH interpretation in invasive breast cancers with immunohistochemically (IHC) equivocal results. 1810 breast cancer cases with IHC equivocal results were enrolled in this study between January 2012 and May 2019. Concomitant IHC was performed on the same tissue blocks detected by FISH testing. According to the 2018 guidelines, all the cases in ISH group 2 were categorized as HER2 negative; three of four cases in ISH group 3 were considered as HER2 positive, while the one scored IHC 1+ was reclassified as HER2 negative; Fifty-three previously ISH equivocal cases were redistributed into ten HER2-positive cases and forty-three HER2-negative cases. In conclusion, the utility of 2018 ASCO/CAP guidelines resulted in a slight decrease in HER2 positive rate, due to the reclassification of cases in ISH group 2 and group 4. The implementation of the new guidelines can reduce reflex FISH test and make the diagnosis of HER2 gene status more definitive.

Clinical outcome and toxicity from taxanes in breast cancer patients with BRCA1 and BRCA2 pathogenic germline mutations

“…Nuclear staining ≥1% of either ER or PR was considered positive. Human epidermal growth factor receptor 2 (HER2) positivity was defined as 3+ receptor overexpression by IHC staining and/or as gene amplification by fluorescence in situ hybridization (FISH) according with CAP/ASCO definition 16 …”

Impact of 2018 ASCO/CAP guidelines on HER‐2 reporting categories of IHC and reflex FISH in breast cancer

“…Wang et al 11 have evaluated the reflex FISH test from 1810 IBC cases., and the overall positive rate dropped from 19.4% (2013 guidelines) to 18.6% due to reclassification of cases in ISH group 2 (1.6%) and group 4 (2.92%).…”

“…8 Although few studies have assiduously evaluated the impact of these 2018 updated ASCO/CAP guidelines, the implications of the same in the clinical practice are still enigmatic. [9][10][11][12][13][14][15] In this presented study, we evaluated the impact of 2018 ASCO/ CAP guidelines for HER-2 testing in IBC on various HER-2 scoring categories by up-front IHC testing and reflex FISH testing for equivocal cases.…”

“…Although few studies have assiduously evaluated the impact of these 2018 updated ASCO/CAP guidelines, the implications of the same in the clinical practice are still enigmatic 9‐15 …”

De-escalation of neoadjuvant therapy for HER2-positive early breast cancer: an overview

“…Recently the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) issued a guideline to improve the diagnostic approach to more rigorous interpretation criteria for in situ hybridization (ISH) (2). In practice the new guideline resulted in a slight decrease in HER2 positive (HER2 + ) rate (3). Continuous refinement of HER2 testing is critical for example to identify tumors that display heterogeneity of HER2 expression and which represents a distinct subset of HER2 + BC associated with resistance to anti-HER2 therapies (4).…”