Assessment of a Genomic Assay in Patients With ERBB2-Positive Breast Cancer Following Neoadjuvant Trastuzumab-Based Chemotherapy With or Without Pertuzumab.

Autor:	Bueno-Muiño C; Medical Oncology Department, Hospital Infanta Cristina (Parla), Fundación de Investigación Biomédica del H.U. Puerta de Hierro, Majadahonda, Madrid, Spain., Echavarría I; Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, Madrid, Spain., López-Tarruella S; Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, Geicam, Universidad Complutense, Madrid, Spain., Roche-Molina M; Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain., Del Monte-Millán M; Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, Madrid, Spain., Massarrah T; Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, Madrid, Spain., Jerez Y; Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, Madrid, Spain., Ayala de la Peña F; Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain., García-Sáenz JÁ; Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, CIBERONC, Madrid, Spain., Moreno F; Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos, CIBERONC, Madrid, Spain., Rodríguez-Lescure Á; Medical Oncology Department, General Universitario de Elche, Alicante, Spain., Malón-Giménez D; Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain., Ballesteros García AI; Department of Medical Oncology, Hospital Universitario de La Princesa, Madrid, Spain., Marín-Aguilera M; Reveal Genomics, Barcelona, Spain., Galván P; Translational Genomics and Targeted Therapies in Solid Tumors, Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain., Brasó-Maristany F; Translational Genomics and Targeted Therapies in Solid Tumors, Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain., Waks AG; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Tolaney SM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Mittendorf EA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts., Vivancos A; Cancer Genomics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain., Villagrasa P; Reveal Genomics, Barcelona, Spain., Parker JS; Department of Genetics, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill., Perou CM; Department of Genetics, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill., Paré L; Reveal Genomics, Barcelona, Spain., Villacampa G; Reveal Genomics, Barcelona, Spain., Prat A; Reveal Genomics, Barcelona, Spain.; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain.; Department of Medical Oncology, Hospital Clinic of Barcelona, Spain.; Institute of Oncology-Quirón, Barcelona, Spain., Martín M; Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, Geicam, Universidad Complutense, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2023 Jun 01; Vol. 9 (6), pp. 841-846.
DOI:	10.1001/jamaoncol.2023.0187
Abstrakt:	Importance: Biomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed. Objective: To determine if use of the HER2DX genomic assay (Reveal Genomics) in pretreatment baseline tissue samples of patients with ERBB2-positive breast cancer is associated with response to neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. Design, Setting, and Participants: This is a retrospective diagnostic/prognostic analysis of a multicenter academic observational study in Spain performed during 2018 to 2022 (GOM-HGUGM-2018-05). In addition, a combined analysis with 2 previously reported trials of neoadjuvant cohorts with results from the assay (DAPHNe and I-SPY2) was performed. All patients had stage I to III ERBB2-positive breast cancer, signed informed consent, and had available formalin-fixed paraffin-embedded tumor specimens obtained prior to starting therapy. Exposures: Patients received intravenous trastuzumab, 8 mg/kg, loading dose, followed by 6 mg/kg every 3 weeks in combination with intravenous docetaxel, 75 mg/m2, every 3 weeks and intravenous carboplatin area under the curve of 6 every 3 weeks for 6 cycles, or this regimen plus intravenous pertuzumab, 840 mg, loading dose, followed by an intravenous 420-mg dose every 3 weeks for 6 cycles. Main Outcome and Measures: Association of baseline assay-reported pathologic complete response (pCR) score with pCR in the breast and axilla, as well as association of baseline assay-reported pCR score with response to pertuzumab. Results: The assay was evaluated in 155 patients with ERBB2-positive breast cancer (mean [range] age, 50.3 [26-78] years). Clinical T1 to T2 and node-positive disease was present in 113 (72.9%) and 99 (63.9%) patients, respectively, and 105 (67.7%) tumors were hormone receptor positive. The overall pCR rate was 57.4% (95% CI, 49.2%-65.2%). The proportion of patients in the assay-reported pCR-low, pCR-medium, and pCR-high groups was 53 (34.2%), 54 (34.8%), and 48 (31.0%), respectively. In the multivariable analysis, the assay-reported pCR score (as a continuous variable from 0-100) showed a statistically significant association with pCR (odds ratio [OR] per 10-unit increase, 1.43; 95% CI, 1.22-1.70; P < .001). The pCR rates in the assay-reported pCR-high and pCR-low groups were 75.0% and 28.3%, respectively (OR, 7.85; 95% CI, 2.67-24.91; P < .001). In the combined analysis (n = 282), an increase in pCR rate due to pertuzumab was found in the assay-reported pCR-high tumors (OR, 5.36; 95% CI, 1.89-15.20; P < .001) but not in the assay-reported pCR-low tumors (OR, 0.86; 95% CI, 0.30-2.46; P = .77). A statistically significant interaction between the assay-reported pCR score and the effect of pertuzumab in pCR was observed. Conclusions and Relevance: This diagnostic/prognostic study demonstrated that the genomic assay predicted pCR following neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. This assay could guide therapeutic decisions regarding the use of neoadjuvant pertuzumab.
Databáze:	MEDLINE
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