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

• Published in: Modern pathology Vol. 34; no. 7; pp. 1271 - 1281
• Main Authors: Katayama, Ayaka, Miligy, Islam M., Shiino, Sho, Toss, Michael S., Eldib, Karim, Kurozumi, Sasagu, Quinn, Cecily M., Badr, Nahla, Murray, Ciara, Provenzano, Elena, Callagy, Grace, Martyn, Cian, Millican-Slater, Rebecca, Purdie, Colin, Purnell, Dave, Pinder, Sarah E., Oyama, Tetsunari, Shaaban, Abeer M., Ellis, Ian, Lee, Andrew H.S., Rakha, Emad A.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.07.2021; Nature Publishing Group US; Elsevier Limited
• Subjects: 13/51; 38/32; 631/67/1059/602; 631/67/1059/99; 631/67/1347; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Chemotherapy; Chemotherapy, Adjuvant - methods; Discordance; Epidermal growth factor; ErbB-2 protein; Female; Fluorescence in situ hybridization; Humans; Immunohistochemistry; Invasiveness; Laboratory Medicine; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy - methods; Pathology; Patients; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - metabolism; Surgery; Treatment Outcome; Tumors
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-021-00738-5

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.