Genomic Characterization and Prognostic Significance of Human Epidermal Growth Factor Receptor 2-Low, Hormone Receptor-Positive, Early Breast Cancers From the BIG 1-98 and SOFT Clinical Trials
- Author(s)
- Luen, SJ; Brown, LC; van Geelen, CT; Savas, P; Kammler, R; Dell'Orto, P; Biasi, O; Coates, AS; Gelber, RD; Thurlimann, B; Colleoni, M; Fleming, GF; Francis, PA; Regan, MM; Viale, G; Loi, S;
- Journal Title
- JCO Precision Oncology
- Publication Type
- Research article
- Abstract
- PURPOSE: To investigate whether hormone receptor-positive, human epidermal growth factor receptor 2-low (HR+HER2-low) versus HR+HER2-zero early breast cancers have distinct genomic and clinical characteristics. METHODS: This study included HR+, HER2-negative early breast cancers from patients enrolled in the phase III, randomized BIG 1-98 and SOFT clinical trials that had undergone tumor genomic sequencing. Tumors were classified HR+HER2-low if they had a centrally reviewed HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization and HR+HER2-zero if they had an HER2 IHC score of 0. RESULTS: A total of 1,795 tumors were evaluable for this study (BIG 1-98 n = 520, SOFT n = 1,275). The frequency of HER2-low tumors was 37% and 21% in the postmenopausal BIG 1-98 and premenopausal SOFT cohorts, respectively. There were no significant differences in clinicopathologic variables between HER2-low and HER2-zero groups which was consistent across both trials. There was no significant difference in risk of distant recurrence for patients with HER2-low tumors versus HER2-zero tumors (5-year % distant recurrence-free 94.0% v 92.8%, P = .61, in BIG 1-98; 89.4% v 92.7%, P = .31, in SOFT, respectively). Somatic genomic profiles were similar with the exception of MAP3K1 mutations which were more frequent in HER2-zero tumors (BIG 1-98 19% v 5%, SOFT 11% v 6%). Both ERBB2 copy number and ERBB2 gene expression abundance were significantly higher in HER2-low tumors compared with HER2-zero tumors; however, the absolute difference was small. Correlation between ERBB2 copy number values and gene expression was modest (r = 0.17). CONCLUSION: In two large clinical trials with centrally reviewed HER2 IHC, our findings do not support HER2-low breast cancer as a distinct clinical or biologic entity among HR+HER2- early breast cancers. Absolute differences in median ERBB2 copy number levels or gene expression are small and of unclear biologic relevance.
- Publisher
- American Society of Clinical Oncology
- Keywords
- Humans; *Breast Neoplasms/genetics/pathology; Female; *Receptor, ErbB-2/genetics/analysis; Middle Aged; Prognosis; Aged; Adult; Genomics; Receptors, Estrogen/analysis; Receptors, Progesterone/analysis
- Department(s)
- Medical Oncology
- PubMed ID
- 39854658
- Publisher's Version
- https://doi.org/10.1200/PO-24-00599
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-04-08 06:06:16
Last Modified: 2025-04-08 06:21:00