Jackie07
02-23-2012, 02:28 AM
Loss of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Metastatic Sites of HER2-Overexpressing Primary Breast Tumors
Naoki Niikura (http://jco.ascopubs.org/search?author1=Naoki+Niikura&sortspec=date&submit=Submit),
Jun Liu (http://jco.ascopubs.org/search?author1=Jun+Liu&sortspec=date&submit=Submit),
Naoki Hayashi (http://jco.ascopubs.org/search?author1=Naoki+Hayashi&sortspec=date&submit=Submit),
Elizabeth A. Mittendorf (http://jco.ascopubs.org/search?author1=Elizabeth+A.+Mittendorf&sortspec=date&submit=Submit),
Yun Gong (http://jco.ascopubs.org/search?author1=Yun+Gong&sortspec=date&submit=Submit),
Shana L. Palla (http://jco.ascopubs.org/search?author1=Shana+L.+Palla&sortspec=date&submit=Submit),
Yutaka Tokuda (http://jco.ascopubs.org/search?author1=Yutaka+Tokuda&sortspec=date&submit=Submit),
Ana M. Gonzalez-Angulo (http://jco.ascopubs.org/search?author1=Ana+M.+Gonzalez-Angulo&sortspec=date&submit=Submit),
Gabriel N. Hortobagyi (http://jco.ascopubs.org/search?author1=Gabriel+N.+Hortobagyi&sortspec=date&submit=Submit) and
Naoto T. Ueno (http://jco.ascopubs.org/search?author1=Naoto+T.+Ueno&sortspec=date&submit=Submit)⇓ (http://jco.ascopubs.org/content/30/6/593#corresp-1)
+ (http://jco.ascopubs.org/content/30/6/593#) Author Affiliations
Naoki Niikura, Jun Liu, Naoki Hayashi, Elizabeth A. Mittendorf, Yun Gong, Shana L. Palla, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi, and Naoto T. Ueno, The University of Texas MD Anderson Cancer Center, Houston, TX; and Naoki Niikura and Yutaka Tokuda, Tokai University School of Medicine, Kanagawa, Japan.
Corresponding author: Naoto T. Ueno, MD, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1354, Houston, TX 77030; e-mail: nueno@mdanderson.org.
Abstract
Purpose We evaluated whether patients with human epidermal growth factor receptor 2 (HER2) –positive primary breast tumors had metastatic tumors that were HER2 positive (concordant) or HER2 negative (discordant). We then evaluated whether treatment with trastuzumab or chemotherapy before biopsy of the metastasis had any effect on the rate of HER2 discordance. We also compared the overall survival durations of patients with HER2-concordant and -discordant tumors.
Patients and Methods We retrospectively identified all patients who initially had been diagnosed with HER2-positive (immunohistochemistry 3+ and/or fluorescent in situ hybridization positive) primary breast cancer between 1997 and 2008 at MD Anderson Cancer Center who also had metastatic tumor biopsy results available for review.
Results We included 182 patients who met our criteria. Forty-three (24%) of the 182 patients with HER2-positive primary tumors had HER2-negative metastatic tumors. The HER2 discordance rates differed significantly on the basis of whether patients received chemotherapy (P = .022) but not on the basis of whether patients received trastuzumab (P = .296). Patients with discordant HER2 status had shorter overall survival than did patients with concordant HER2 status (hazard ratio [HR], 0.43; P = .003). A survival difference remained among the 67 patients who received trastuzumab (HR, 0.56; P = .083) and 101 patients who did not (HR, 0.53; P = .033) before their metastasis biopsies.
Conclusion We confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy.
Footnotes
See accompanying editorial on page 575 (http://jco.ascopubs.org/lookup/doi/10.1200/JCO.2011.36.6385) and article on page 587 (http://jco.ascopubs.org/lookup/doi/10.1200/JCO.2010.33.5232); listen to the podcast by Dr Davidson at www.jco.org/podcasts (http://www.jco.org/podcasts)
Supported in part by Grant No. CA016672 from the National Institutes of Health through MD Anderson Cancer Center support, and by the Nellie B. Connally Breast Cancer Research Fund.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Received November 24, 2010.
Accepted August 24, 2011.
Published online before print November 28, 2011, doi: 10.1200/JCO.2010.33.8889 JCO February 20, 2012 vol. 30 no. 6 593-599
Naoki Niikura (http://jco.ascopubs.org/search?author1=Naoki+Niikura&sortspec=date&submit=Submit),
Jun Liu (http://jco.ascopubs.org/search?author1=Jun+Liu&sortspec=date&submit=Submit),
Naoki Hayashi (http://jco.ascopubs.org/search?author1=Naoki+Hayashi&sortspec=date&submit=Submit),
Elizabeth A. Mittendorf (http://jco.ascopubs.org/search?author1=Elizabeth+A.+Mittendorf&sortspec=date&submit=Submit),
Yun Gong (http://jco.ascopubs.org/search?author1=Yun+Gong&sortspec=date&submit=Submit),
Shana L. Palla (http://jco.ascopubs.org/search?author1=Shana+L.+Palla&sortspec=date&submit=Submit),
Yutaka Tokuda (http://jco.ascopubs.org/search?author1=Yutaka+Tokuda&sortspec=date&submit=Submit),
Ana M. Gonzalez-Angulo (http://jco.ascopubs.org/search?author1=Ana+M.+Gonzalez-Angulo&sortspec=date&submit=Submit),
Gabriel N. Hortobagyi (http://jco.ascopubs.org/search?author1=Gabriel+N.+Hortobagyi&sortspec=date&submit=Submit) and
Naoto T. Ueno (http://jco.ascopubs.org/search?author1=Naoto+T.+Ueno&sortspec=date&submit=Submit)⇓ (http://jco.ascopubs.org/content/30/6/593#corresp-1)
+ (http://jco.ascopubs.org/content/30/6/593#) Author Affiliations
Naoki Niikura, Jun Liu, Naoki Hayashi, Elizabeth A. Mittendorf, Yun Gong, Shana L. Palla, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi, and Naoto T. Ueno, The University of Texas MD Anderson Cancer Center, Houston, TX; and Naoki Niikura and Yutaka Tokuda, Tokai University School of Medicine, Kanagawa, Japan.
Corresponding author: Naoto T. Ueno, MD, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1354, Houston, TX 77030; e-mail: nueno@mdanderson.org.
Abstract
Purpose We evaluated whether patients with human epidermal growth factor receptor 2 (HER2) –positive primary breast tumors had metastatic tumors that were HER2 positive (concordant) or HER2 negative (discordant). We then evaluated whether treatment with trastuzumab or chemotherapy before biopsy of the metastasis had any effect on the rate of HER2 discordance. We also compared the overall survival durations of patients with HER2-concordant and -discordant tumors.
Patients and Methods We retrospectively identified all patients who initially had been diagnosed with HER2-positive (immunohistochemistry 3+ and/or fluorescent in situ hybridization positive) primary breast cancer between 1997 and 2008 at MD Anderson Cancer Center who also had metastatic tumor biopsy results available for review.
Results We included 182 patients who met our criteria. Forty-three (24%) of the 182 patients with HER2-positive primary tumors had HER2-negative metastatic tumors. The HER2 discordance rates differed significantly on the basis of whether patients received chemotherapy (P = .022) but not on the basis of whether patients received trastuzumab (P = .296). Patients with discordant HER2 status had shorter overall survival than did patients with concordant HER2 status (hazard ratio [HR], 0.43; P = .003). A survival difference remained among the 67 patients who received trastuzumab (HR, 0.56; P = .083) and 101 patients who did not (HR, 0.53; P = .033) before their metastasis biopsies.
Conclusion We confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy.
Footnotes
See accompanying editorial on page 575 (http://jco.ascopubs.org/lookup/doi/10.1200/JCO.2011.36.6385) and article on page 587 (http://jco.ascopubs.org/lookup/doi/10.1200/JCO.2010.33.5232); listen to the podcast by Dr Davidson at www.jco.org/podcasts (http://www.jco.org/podcasts)
Supported in part by Grant No. CA016672 from the National Institutes of Health through MD Anderson Cancer Center support, and by the Nellie B. Connally Breast Cancer Research Fund.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Received November 24, 2010.
Accepted August 24, 2011.
Published online before print November 28, 2011, doi: 10.1200/JCO.2010.33.8889 JCO February 20, 2012 vol. 30 no. 6 593-599