Cited by 331HER2/EGFR in Cancer ResearchBreast Cancer Treatment StudiesGastric Cancer Management and Outcomes

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Loss of HER2 Amplification Following Trastuzumab-Based Neoadjuvant Systemic Therapy and Survival Outcomes

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Mittendorf, Elizabeth A., Wu, Yun, Scaltriti, Maurizio, Meric-Bernstam, Funda, Hunt, Kelly K., Dawood, Shaheenah, Esteva, Francisco J., Buzdar, Aman U., Chen, Huiqin, Eksambi, Sameena, Hortobagyi, Gabriel N., Baselga, Jose, Gonzalez-Angulo, Ana M.·2009·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-09-1735PMC PMC2788123

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Abstract

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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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: Mittendorf, Elizabeth A.
Wu, Yun
Scaltriti, Maurizio
Hunt, Kelly K.
Dawood, Shaheenah
Esteva, Francisco J.
Buzdar, Aman U.
Chen, Huiqin
Baselga, Jose
Gonzalez-Angulo, Ana M.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2009-11-30
Volume: 15
Issue: 23
Pages: 7381-7388
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-09-1735
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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Loss of HER2 Amplification Following Trastuzumab-Based Neoadjuvant Systemic Therapy and Survival Outcomes

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