Comparison of HER-2 Overexpression in Primary Breast Cancer and Metastatic Sites and Its Effect on Biological Targeting Therapy of Metastatic Disease

Overview

Journal Br J Cancer

Specialty Oncology

Date 2005 Aug 18

PMID 16106267

Citations 92

Authors

J Zidan

I Dashkovsky

C Stayerman

W Basher

C Cozacov

A Hadary

Affiliations

Soon will be listed here.

Abstract

HER-2 overexpression, a predictive marker of tumour aggressiveness and responsiveness to therapy, occurs in 20-30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 measurement is carried out in primary tumour. This study aims to evaluate HER-2 overexpression in primary and metastases and its effect on treatment decisions. Biopsies from primary breast cancer and corresponding metastases from 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically in all primary and metastatic sites. Positive overexpression in primary and/or metastases was confirmed by fluorescence in situ hybridisation (FISH). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (eight of 58 patients). Concordance was found in 50 (86%) of patients (95% CI: 77-95). In one patient (2%), HER-2 was negative in metastasis but positive in primary. In seven (12%) patients, HER-2 was positive in metastases and negative in primary (95% CI: 3.7-20), and three of them responded to trastuzumab. Gene amplification by FISH was found in all cases with HER-2 positive (+2 and +3) by immunohistochemistry. Our data suggest that a possible discordance of HER-2 overexpression between primary and metastases should be considered when making treatment decisions in patients with primary HER-2-negative tumours.

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References

Ross , Fletcher . The HER-2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy. Oncologist. 1999; 3(4):237-252. View

Slamon D, Clark G, Wong S, Levin W, Ullrich A, McGuire W . Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785):177-82. DOI: 10.1126/science.3798106. View

Niehans G, Singleton T, Dykoski D, Kiang D . Stability of HER-2/neu expression over time and at multiple metastatic sites. J Natl Cancer Inst. 1993; 85(15):1230-5. DOI: 10.1093/jnci/85.15.1230. View

Baselga J . Phase I and II clinical trials of trastuzumab. Ann Oncol. 2001; 12 Suppl 1:S49-55. DOI: 10.1093/annonc/12.suppl_1.s49. View

Shimizu C, Fukutomi T, Tsuda H, Akashi-Tanaka S, Watanabe T, Nanasawa T . c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues. J Surg Oncol. 2000; 73(1):17-20. DOI: 10.1002/(sici)1096-9098(200001)73:1<17::aid-jso5>3.0.co;2-2. View

Andrulis I, Bull S, Blackstein M, Sutherland D, Mak C, SIDLOFSKY S . neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol. 1998; 16(4):1340-9. DOI: 10.1200/JCO.1998.16.4.1340. View

Thor A, Berry D, Budman D, Muss H, Kute T, Henderson I . erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst. 1998; 90(18):1346-60. DOI: 10.1093/jnci/90.18.1346. View

Masood S, Bui M . Assessment of Her-2/neu overexpression in primary breast cancers and their metastatic lesions: an immunohistochemical study. Ann Clin Lab Sci. 2000; 30(3):259-65. View

Gancberg D, Di Leo A, Cardoso F, Rouas G, Pedrocchi M, Paesmans M . Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann Oncol. 2002; 13(7):1036-43. DOI: 10.1093/annonc/mdf252. View

10.

Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D . erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998; 90(18):1361-70. DOI: 10.1093/jnci/90.18.1361. View

11.

Gutierrez M, Detre S, Johnston S, Mohsin S, Shou J, Allred D . Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase. J Clin Oncol. 2005; 23(11):2469-76. DOI: 10.1200/JCO.2005.01.172. View

12.

Hortobagyi G . Optimal duration of therapy with trastuzumab. Semin Oncol. 2001; 28(5 Suppl 16):33-40. DOI: 10.1016/s0093-7754(01)90280-5. View

13.

Kuukasjarvi T, Karhu R, Tanner M, Kahkonen M, Schaffer A, Nupponen N . Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer. Cancer Res. 1997; 57(8):1597-604. View

14.

Dandachi N, Dietze O, Hauser-Kronberger C . Evaluation of the clinical significance of HER2 amplification by chromogenic in situ hybridisation in patients with primary breast cancer. Anticancer Res. 2004; 24(4):2401-6. View

15.

Tanner M, Jarvinen P, Isola J . Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. Cancer Res. 2001; 61(14):5345-8. View

16.

Lohrisch C, Piccart M . An overview of HER2. Semin Oncol. 2002; 28(6 Suppl 18):3-11. View

17.

Nicholson R, McClelland R, Finlay P, Eaton C, Gullick W, Dixon A . Relationship between EGF-R, c-erbB-2 protein expression and Ki67 immunostaining in breast cancer and hormone sensitivity. Eur J Cancer. 1993; 29A(7):1018-23. DOI: 10.1016/s0959-8049(05)80215-1. View

18.

Burstein H, Harris L, Marcom P, Lambert-Falls R, Havlin K, Overmoyer B . Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm. J Clin Oncol. 2003; 21(15):2889-95. DOI: 10.1200/JCO.2003.02.018. View

19.

Leitzel K, Teramoto Y, Konrad K, Chinchilli V, Volas G, Grossberg H . Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer. J Clin Oncol. 1995; 13(5):1129-35. DOI: 10.1200/JCO.1995.13.5.1129. View

20.

Slamon D, Godolphin W, Jones L, Holt J, Wong S, Keith D . Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989; 244(4905):707-12. DOI: 10.1126/science.2470152. View