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Loss of HER2 Amplification Following Trastuzumab-Based Neoadjuvant Systemic Therapy and Survival Outcomes
Open accessAbstract
PURPOSE: To evaluate HER2 status in residual tumor identified at the time of surgery in patients not achieving a pathologic complete response (pCR) and to determine the effect of alterations in HER2 status on recurrence-free survival (RFS). EXPERIMENTAL DESIGN: Clinicopathologic data for patients with HER2-overexpressing breast cancer receiving neoadjuvant therapy with a taxane, anthracycline, and concomitant trastuzumab between 2004 and 2007 were reviewed. Surgical specimens for patients achieving less than a pCR were assessed to determine if there was enough residual tissue to evaluate posttreatment HER2 status. RFS was determined using the Kaplan-Meier method and compared by the log-rank statistic. RESULTS: A pCR was achieved in 72 of the 142 (50.7%) patients. Residual tumor was sufficient to assess posttreatment HER2 status in 25 patients. Fluorescence in situ hybridization done on pretreatment specimens confirmed HER2 amplification before beginning therapy. Eight (32.0%) posttreatment tumors were found to be HER2-negative by fluorescence in situ hybridization. At a median follow-up of 37 months (range, 8-56 months), the RFS was significantly better for patients with tumors that retained HER2 amplification (87.5% versus 50%, P = 0.04). CONCLUSION: High pCR rates are achieved in patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab in combination with anthracyclines and taxanes. One third of patients with significant residual disease loses HER2 amplification, and this change is associated with poor RFS. Residual tumor identified at the time of surgery should be reassessed for HER2 status, and novel adjuvant therapy strategies need to be studied in this population.
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“some patients with HER2+ tumors convert to HER2-negative following neoadjuvant trastuzumab and chemotherapy”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Mittendorf et al., 2009
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“these patients exhibit a shorter relapse-free survival compared to those with residual tumors that remain HER2 amplified (Hurley et al., 2006; Mittendorf et al., 2009).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Mittendorf et al., 2009
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Metadata
- Authors
- Mittendorf, E. A., Wu, Y., Scaltriti, M., Meric-Bernstam, F., Hunt, K. K., Dawood, S., Esteva, F. J., Buzdar, A. U., Chen, H., Eksambi, S., Hortobagyi, G. N., Baselga, J., & Gonzalez-Angulo, A. M.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Authors' Affiliations: Departments of 1Surgical Oncology, 2Pathology, 3Breast Medical Oncology, and 4Systems Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and 5Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain
- Corresponding author
- Gonzalez-Angulo, Ana M.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2009-11-30
- Volume
- 15
- Issue
- 23
- Pages
- 7381-7388
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC2788123
- OpenAlex
- W2140927379
- Cited by
- 330
- References
- 31
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 20 · 2023: 27 · 2022: 24 · 2021: 29 · 2020: 20 · 2019: 20 · 2018: 12 · 2017: 10 · 2016: 17 · 2015: 23 · 2014: 18 · 2013: 25 · 2012: 23
- FWCI
- 9.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k23ca121994-03, 1k99ca133244-01)
- National Cancer Institute (1K23CA121994-01), 1K99CA133244-01, K99 CA133244, K23-CA121994, 1K23CA121994)
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
- Keywords
- HER2 amplification, trastuzumab, neoadjuvant therapy, HER2-positive breast cancer, pathological complete response, residual tumor, recurrence-free survival, anthracyclines, taxanes, fluorescence in situ hybridization
- MeSH terms
- Trastuzumab, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Female, Humans, Middle Aged, Recurrence, Treatment Outcome, Disease-Free Survival, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Anthracyclines, Neoadjuvant Therapy, Taxoids, Cell Line, Tumor, Antibodies, Monoclonal, Humanized
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