This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arnould, L. Articles by Coudert, B. P. Search for Related Content PubMed PubMed Citation Articles by Arnould, L. Articles by Coudert, B. P.

Pathologic Complete Response to Trastuzumab-Based Neoadjuvant Therapy Is Related to the Level of HER-2 Amplification

Authors' Affiliations: ¹ CLCC G-F Leclerc and 1FR100, Dijon, France; ² CLCC Institut Curie; ³ Hôpital Tenon, Paris, France; ⁴ CLCC A Lacassagne, Nice, France; ⁵ Hopital Laënnec, Nantes, France; ⁶ CLCC Jean Perrin, Clermont-Ferrand, France; and ⁷ Laboratoire Roche-Pharma, Neuilly sur Seine, France

Requests for reprints: Laurent Arnould, Department of Pathology, Centre G-F Leclerc, 1 Rue Pr Marion, 21000 Dijon Cedex, France. Phone: 33-380-737-723; Fax: 33-380-737-717; E-mail: larnould{at}dijon.fnclcc.fr.

Purpose: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer.

Experimental Design: Breast biopsies from 93 HER-2–positive patients treated with trastuzumab-based neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+.

Results: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low- and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low- plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen, T or N stage, tumor grade, or hormonal receptors.

Conclusions: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.

This article has been cited by other articles:

				M. Kakarala and M. S. Wicha Implications of the Cancer Stem-Cell Hypothesis for Breast Cancer Prevention and Therapy J. Clin. Oncol., June 10, 2008; 26(17): 2813 - 2820. [Abstract] [Full Text] [PDF]