Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer

Ayaka Katayama, Islam M. Miligy, Sho Shiino, Michael S. Toss, Karim Eldib, Sasagu Kurozumi, Cecily M. Quinn, Nahla Badr, Ciara Murray, Elena Provenzano, Grace Callagy, Cian Martyn, Rebecca Millican-Slater, Colin Purdie, Dave Purnell, Sarah E. Pinder, Tetsunari Oyama, Abeer M. Shaaban, Ian Ellis, Andrew H. S. LeeEmad A. Rakha

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
7 Downloads (Pure)

Abstract

The response of human epidermal growth factor receptor2 (HER2)- positive breast cancer (BC) patients to anti-HER2 targeted therapy is significant. However, the response is not uniform and a proportion of HER2-positive patients do not respond. This study aims to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive BC patients. The study group comprised 500 BC patients treated with neoadjuvant chemotherapy (NACT) and/or neoadjuvant anti-HER2 therapy and surgery who had tumours that were 3+ or 2+ with HER2 immunohistochemistry (IHC). HER2 IHC 2+ tumours were classified into five groups by fluorescence in situ hybridisation (FISH) according to the 2018 ASCO/CAP guidelines of which Groups 1, 2 and 3 were considered HER2 amplified. Pathological complete response (pCR) was more frequent in HER2 IHC 3+ tumours than in HER2 IHC 2+/HER2 amplified tumours, when either in receipt of NACT alone (38% versus 13%; p = 0.22) or neoadjuvant anti-HER2 therapy (52% versus 20%; p < 0.001). Multivariate logistic regression analysis showed that HER2 IHC 3+ and histological grade 3 were independent predictors of pCR following neoadjuvant anti-HER2 therapy. In the HER2 IHC 2+/HER2 amplified tumours or ASCO/CAP FISH Group 1 alone, ER-negativity was an independent predictor of pCR following NACT and/or neoadjuvant anti-HER2 therapy. In the current study, 22% of HER2-positive tumours became HER2-negative by IHC and FISH following neoadjuvant treatment, the majority (74%) HER2 IHC 2+/HER2 amplified tumours. Repeat HER2 testing after neoadjuvant treatment should therefore be considered.

Original languageEnglish
Pages (from-to)1271-1281
Number of pages11
JournalModern Pathology
Volume34
Early online date1 Feb 2021
DOIs
Publication statusE-pub ahead of print - 1 Feb 2021

Keywords

  • Breast cancer
  • Chemotherapy
  • Targeted therapies

Fingerprint

Dive into the research topics of 'Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer'. Together they form a unique fingerprint.

Cite this