Long-term prognostic significance of HER2-low-positive and HER2-zero in node-negative breast cancer

Aim HER2 is an important prognostic and predictive factor in breast cancer. Recently, novel antibody-drug-conjugates (ADCs) showed clinical activity not only in HER2-positive but also in HER2-low patients. In this study, we investigated the prognostic significance of HER2-low and HER2-zero patients.

Methods The study cohort included 410 consecutive node-negative breast cancer patients without adjuvant systemic therapy treated between 1985 and 2000 (median follow-up 16,7 years [interquartile range 8.58–23.45]). The prognostic impact of the HER2-status was examined with Cox-regression analyses and Kaplan-Meier method.

Findings 198 (56.4%) of 351 HER2-negative patients had HER2-low-positive tumours and 153 (43.6%) were HER2-zero. HER2-low-positive patients had a significant longer disease-free survival (DFS) (15-year rate: 67.5% vs. 47.3%, P<0.001) and overall survival (OS) (15-year rate: 75.4% vs. 66.8%, P=0.009) than HER2-zero patients. This survival difference was also seen in the subgroup of hormone receptor (HR)-positive patients (15-year DFS: 67.5% vs. 48.0%, P<0.001; 15-year OS: 75.5% vs. 65.6%, P=0.039). Results of multivariable analyses confirmed the independent prognostic relevance of the HER2-status (DFS: HR 0.540, 95% CI 0.397–0.735, P<0.001; OS: HR 0.646, 95% CI 0.453-0.920, P=0.016).

Conclusion Our results argue for additional clinically relevant subtypes of HER2-negative breast cancer, HER2-low-positive and HER2-zero. In particular, the low HER2-positive patients may be suitable candidates for novel ADCs.

Interessenskonflikt Details  Katrin Almstedt received speaker honoraria from Roche Pharma AG, Pfizer Pharma GmbH and AstraZeneca.Anne-Sophie Heimes received speaker honoraria from Pfizer Pharma GmbH and honoraria from Med update GmbH.Marco J. Battista received honoraria and expenses from Astra Zeneca, Clovis Oncology, GSK, MSD, Pharma Mar, Roche and Tesaro Bio Germany GmbH. He is consultant to Eisai, GSK, MSD, Pharma Mar, Roche Pharma AG and Tesaro Bio Germany GmbH. He received funded research from Astra Zeneca, Clovis Oncology, MSD and Novartis.Slavomir Krajnak received speaker honoraria from Roche Pharma AG and Novartis Pharma GmbH Germany, research funding from Novartis Pharma GmbH Germany and travel reimbursement from PharmaMar and Novartis Pharma GmbH Germany.Annette Hasenburg received honoraria from AstraZeneca, Celegen, MedConcept Gm, Med update GmbH, Medicultus, Pfizer, Roche Pharma AG, Streamedup!GmbH, Tesaro Bio Germany GmbH, LEO Pharma and Clovis Oncology. She is a member of the advisory board of PharmaMar, Roche Pharma AG, Tesaro Bio Germany GmbH, AstraZeneca, LEO Pharma, GSK/MSD.M. Schmidt received honoraria for speaker or consultancy role from AstraZeneca, Daiichi Sankyo, Eisai, Lilly, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche and SeaGen.All other authors declare that they have no conflict of interest.

Publication History

Article published online:
21 June 2022