Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy, with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Abstract

Background The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number &lt;4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT). Methods 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed. Results 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017). Conclusion No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.

Intratumoral Heterogeneity and Immune Response Indicators to Predict Overall Survival in a Retrospective Study of HER2-Borderline (IHC 2+) Breast Cancer Patients

“…Approximately 15%-30% of IHC 2+ cases are HER2amplified (29), while the remaining IHC 2+ and IHC 1+ HER2 non-amplified tumors were recently designated as a relatively common "HER2-low" category, accounting for approximately 40%-55% of BC (30)(31)(32). This concept becomes important with the advent of a new generation of anti-HER2 agents.…”

Improved concordance of challenging human epidermal growth factor receptor 2 dual in‐situ hybridisation cases with the use of a digital image analysis algorithm in breast cancer

“…The categorisation of five distinct HER2 ISH biological groups from the continuum of HER2 expression in the 2018 ASCO/CAP update highlighted the importance of accurate determination of HER2 status via IHC and ISH testing. Further research is required to evaluate whether these groups benefit from anti‐HER2 therapies to help inform treatment decisions in these patients 13,16–18 . We undertook subgroup analysis to evaluate if particular groups had higher levels of interobserver variability associated with their reporting.…”

“…Further research is required to evaluate whether these groups benefit from anti-HER2 therapies to help inform treatment decisions in these patients. 13,[16][17][18] We undertook subgroup analysis to evaluate if particular groups had higher levels of interobserver variability associated with their reporting. Low concordance was strikingly evident in group 2 and borderline group 5, as pathologist agreement was not significantly different from the agreement that may occur due to random chance.…”

CNA Landscape of HER2-Negative Breast Cancer in Anthracycline-Based Neoadjuvant Chemotherapy Regimens

“…В частности, дупликацию центромеры хромосомы 17 (дупликация CEP17) исследовали в качестве маркера чувствительности к антрациклинам. Повышение количества CEP17 нередко встречается при РМЖ [11,12]. Анализ образцов РМЖ на наличие дупликации CEP17 с различными значениями (например, >1.86 CEP17/клетку, соотношение HER2/CEP17 ≥2.0), выполненный несколькими группами ученых, привел к получению абсолютно противоречивых результатов -наличие/отсутствие линейной зависимости между отношением HER2/CEP17 и pCR [11,13,14].…”