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

• Published in: Clinical cancer research Vol. 15; no. 23; pp. 7381 - 7388
• Main Authors: MITTENDORF, Elizabeth A, YUN WU, HORTOBAGYI, Gabriel N, BASELGA, Jose, GONZALEZ-ANGULO, Ana M, SCALTRITI, Maurizio, MERIC-BERNSTAM, Funda, HUNT, Kelly K, DAWOOD, Shaheenah, ESTEVA, Francisco J, BUZDAR, Aman U, HUIQIN CHEN, EKSAMBI, Sameena
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2009
• Subjects: Adult; Aged; Aged, 80 and over; Anthracyclines - pharmacology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - therapy; Cell Line, Tumor; Disease-Free Survival; Female; HER2/neu; Humans; Medical sciences; Middle Aged; neoadjuvant chemotherapy; Neoadjuvant Therapy - methods; Pharmacology. Drug treatments; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Recurrence; Taxoids - metabolism; Trastuzumab; Treatment Outcome; Antineoplastic agent; Gene amplification; Prognosis; C-Onc gene; erbB2 Gene; Monoclonal antibody; Survival; Protooncogene; Neoadjuvant treatment; Trastuzumab; Human Epidermal growth factor Receptor 2
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-1735

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. (Clin Cancer Res 2009;15(23):7381–8)