BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer.

Autor: Liefaard MC; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van der Voort A; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., van Ramshorst MS; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Sanders J; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Vonk S; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Core Facility Molecular Pathology and Biobanking, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Horlings HM; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Siesling S; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands.; Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, The Netherlands., de Munck L; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands., van Leeuwen AE; Dutch Breast Cancer Research Group, BOOG Study Center, Amsterdam, The Netherlands., Kleijn M; Department of Research and Development, Agendia NV, Amsterdam, The Netherlands., Mittempergher L; Department of Research and Development, Agendia NV, Amsterdam, The Netherlands., Kuilman MM; Department of Research and Development, Agendia NV, Amsterdam, The Netherlands., Glas AM; Department of Research and Development, Agendia NV, Amsterdam, The Netherlands., Wesseling J; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Lips EH; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Sonke GS; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. g.sonke@nki.nl.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2023 Jun 19; Vol. 25 (1), pp. 71. Date of Electronic Publication: 2023 Jun 19.
DOI: 10.1186/s13058-023-01664-x
Abstrakt: Background: The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.
Methods: From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups.
Results: BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes.
Conclusions: In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.
(© 2023. The Author(s).)
Databáze: MEDLINE
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