A retrospective study investigating the rate of HER2 discordance between primary breast carcinoma and locoregional or metastatic disease

BMC Cancer

Arlene Chan²  Adrienne Morey¹  Belinda Brown¹  Diana Hastrich²  Peter Willsher²  David Ingram² 

[1] Sydpath, St Vincent’s Hospital, New South Wales, Australia

[2] Mount Hospital, Perth, WA, 6000, Australia

关键词: Discordance;    Metastatic breast cancer;    HER2;   

Others  :  1080056
DOI  :  10.1186/1471-2407-12-555

 received in 2012-06-19, accepted in 2012-11-16,  发布年份 2012

【 摘 要 】

Background

Overall survival of HER2 positive metastatic breast cancer patients has been significantly improved with inclusion of trastuzumab to chemotherapy. Several studies have demonstrated discordant HER2 status in the primary and metastatic tumour. However, rates of discordance vary considerably in published reports.

Methods

Information collected prospectively was analysed for all patients seen from 1999 to 2009 with primary breast cancer and who had biopsy of a local or distant recurrence. Patients were included if adequate tissue was available from both paired samples. Recurrent samples included fine needle aspirations, core and excisional biopsies. HER2 status in all paired samples was assessed by in-situ hybridisation by a single pathologist in a national reference laboratory. This was compared with HER2 immunohistochemistry results provided in the course of routine diagnosis at regional laboratories.

Results

In total, 157 patients with recurrent (n = 137; 87.3%) or synchronous primary and metastatic (n = 20; 12.7%) breast cancer had biopsy of the metastatic site. The study population comprised of 116 patients with adequate tissue in both primary and metastasis. The concordance between HER2 status of the paired samples by local immunohistochemistry testing and central in-situ hybridization were 78% and 99%, respectively. Only one patient demonstrated HER2 discordance – primary lesion was positive whilst a metastatic site was negative.

Conclusions

This single institution study demonstrated a low rate of HER2 discordance between primary and recurrent breast cancer as assessed by in-situ hybridisation. This contrasts to results reported by others, which may be explained by differences in study methodology, definition of recurrent disease samples and generally small numbers of patients assessed. Despite the current findings, the decision to obtain metastatic tissue for evaluation is influenced by other factors. These include disease-free interval, which may raise the possibility of a new malignancy and the accuracy of initial HER2 assessment of the primary tumour.

【 授权许可】

   
2012 Chan et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Anton A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM: Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 2005, 23:4265-4274.
• [2]Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001, 344:783-792.
• [3]Aitken SJ, Thomas JS, Langdon SP, Harrison DJ, Faratian D: Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases. Ann Oncol 2010, 21:1254-1261.
• [4]Liedtke C, Broglio K, Moulder S, Hsu L, Kau SW, Symmans WF, Albarracin C, Meric-Bernstam F, Woodward W, Theriault RL, Kiesel L, Hortobagyi GN, Pusztai L, Gonzalez-Angulo AM: Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol 2009, 20:1953-1958.
• [5]Solomayer EF, Becker S, Pergola-Becker G, Bachmann R, Kramer B, Vogel U, Neubauer H, Wallwiener D, Huober J, Fehm TN: Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients. Breast Cancer Res Treat 2006, 98:179-184.
• [6]Fehm T, Becker S, Duerr-Stoerzer S, Sotlar K, Mueller V, Wallwiener D, Lane N, Solomayer E, Uhr J: Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status. Breast Cancer Res 2007, 9:R74. BioMed Central Full Text
• [7]Lipton A, Leitzel K, Ali SM, Demers L, Harvey HA, Chaudri-Ross HA, Evans D, Lang R, Hackl W, Hamer P, Carney W: Serum HER-2/neu conversion to positive at the time of disease progression in patients with breast carcinoma on hormone therapy. Cancer 2005, 104:257-263.
• [8]Giotta F, Simone G, Fazio V, Longo S, Petroni S, Rubini V, Liuzzi M, Addati T, Colucci G: Patterns of HER2/neu, hormonal receptor expression, and proliferative activity in primary and metastatic breast cancer. J Clin Oncol 2009, 27:15s.
• [9]Gancberg D, Di Leo A, Cardoso F, Rouas G, Pedrocchi M, Paesmans M, Verhest A, Bernard-Marty C, Piccart MJ, Larsimont D: Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol 2002, 13:1036-1043.
• [10]Niikura N, Liu J, Hayashi N, Mittendorf EA, Gong Y, Palla SL, Tokuda Y, Gonzalez-Angulo AM, Hortobagyi GN, Ueno NT: Loss of human epidermal growth factor receptor 2 (HER2) expression in metastatic sites of HER2-overexpressing primary breast tumors. J Clin Oncol 2012, 30:593-599.
• [11]Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, Oldfield M, Dranitsaris G, Tomlinson G, Laupacis A, Tannock IF, Clemons M: Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol 2012, 30:587-592.
• [12]Gong Y, Booser DJ, Sneige N: Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma. Cancer 2005, 103:1763-1769.
• [13]Tapia C, Savic S, Wagner U, Schonegg R, Novotny H, Grilli B, Herzog M, Barascud AD, Zlobec I, Cathomas G, Terracciano L, Feichter G, Bubendorf L: HER2 gene status in primary breast cancers and matched distant metastases. Breast Cancer Res 2007, 9:R31. BioMed Central Full Text
• [14]Fabi A, Di Benedetto A, Metro G, Perracchio L, Nistico C, Di Filippo F, Ercolani C, Ferretti G, Melucci E, Buglioni S, Sperduti I, Papaldo P, Cognetti F, Mottolese M: HER2 protein and gene variation between primary and metastatic breast cancer: significance and impact on patient care. Clin Cancer Res 2011, 17:2055-2064.
• [15]Simon R, Nocito A, Hubscher T, et al.: Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer. J Natl Cancer Inst 2001, 93:1141-1146.
• [16]Lindstrom L, Karlsson E, Wilking U, et al.: Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 2012, 30:2601-208.
• [17]Mittendorf EA, Wu Y, Scaltriti M, Meric-Bernstam F, Hunt KK, Dawood S, Esteva FJ, Buzdar AU, Chen H, Eksambi S, Hortobagyi GN, Baselga J, Gonzalez-Angulo AM: Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 2009, 15:7381-7388.
• [18]Vincent-Salomon A, Jouve M, Genin P, Freneaux P, Sigal-Zafrani B, Caly M, Beuzeboc P, Pouillart P, Sastre-Garau X: HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process. Cancer 2002, 94:2169-2173.
• [19]Shousha S, Peston D, Amo-Takyi B, Morgan M, Jasani B: Evaluation of automated silver-enhanced in situ hybridization (SISH) for detection of HER2 gene amplification in breast carcinoma excision and core biopsy specimens. Histopathology 2009, 54:248-253.