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

Abstract

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.

• Authors: Coralia Bueno-Muiño, Isabel Echavarría, Sara López-Tarruella, Marta Roche-Molina, María Del Monte-Millán, Tatiana Massarrah, Yolanda Jerez, Francisco Ayala de la Peña, José Ángel García-Sáenz, Fernando Moreno, Álvaro Rodríguez-Lescure, Diego Malón-Giménez, Ana Isabel Ballesteros García, Mercedes Marín-Aguilera, Patricia Galván, Fara Brasó-Maristany, Adrienne G Waks, Sara M Tolaney, Elizabeth A Mittendorf, Ana Vivancos, Patricia Villagrasa, Joel S Parker, Charles M Perou, Laia Paré, Guillermo Villacampa, Aleix Prat, Miguel Martín
• Journal: JAMA oncology (JAMA Oncol) Vol. 9 Issue 6 Pg. 841-846 (Jun 01 2023) ISSN: 2374-2445 [Electronic] United States
• PMID: 37103916 (Publication Type: Observational Study, Multicenter Study, Journal Article)

Chemical References

• ERBB2 protein, human
• pertuzumab
• Receptor, ErbB-2
• Trastuzumab

Topics

• Female
• Humans
• Middle Aged
• Antineoplastic Combined Chemotherapy Protocols
• Breast Neoplasms (drug therapy, genetics, pathology)
• Genomics
• Neoadjuvant Therapy (methods)
• Receptor, ErbB-2 (genetics, analysis)
• Retrospective Studies
• Trastuzumab (therapeutic use)
• Treatment Outcome