HER-2 Protein Overexpressing Breast Cancer Without Gene Amplification Shows Higher Hormone Receptor Expression Than HER-2 Protein Overexpressing Breast Cancer With Gene Amplification
Restricted accessResearch articleFirst published online August, 2011
HER-2 Protein Overexpressing Breast Cancer Without Gene Amplification Shows Higher Hormone Receptor Expression Than HER-2 Protein Overexpressing Breast Cancer With Gene Amplification
Cases of breast cancer showing human epidermal growth factor receptor-2 (HER-2) protein overexpression without corresponding gene amplification have been found in immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) results. We investigated the clinicopathological characteristics of cases showing HER-2 protein overexpression breast cancer without gene amplification (IHC3+/FISH−) and compared them to cases showing HER-2 protein overexpression breast cancer with gene amplification (IHC3+/FISH+). This study was conducted on 90 patients with HER-2 IHC3+ breast cancer. The clinicopathological factors analyzed included tumor size, histological grade, nuclear grade, nodal involvement, and hormone receptor status. HER-2 IHC3+/FISH− breast cancer was found in 14 of 84 tumors (16.7%) and showed a statistically significant lower histological and nuclear grade (P = .000) and higher expression of estrogen receptors (ERs) and progesterone receptors (PRs) (P = .006) than IHC3+/FISH+ breast cancer. In conclusion, HER-2 IHC3+/FISH− breast cancer could be a subgroup showing lower histological/nuclear grade and higher expression of ERs/PRs.
AllredDCHarveyJMBerardoMClarkGM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155-168.
2.
GaspariniGPozzaFHarrisAL. Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients. J Natl Cancer Inst. 1993;85:1206-1219.
3.
MansourEGRavdinPMDresslerL. Prognostic factors in early breast carcinoma. Cancer. 1994;74:381-400.
4.
SternDFHeffernanPAWeinbergRA. p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Mol Cell Biol. 1986;6:1729-1740.
5.
HannaW. Testing for HER2 status. Oncology. 2001;61Suppl 2:22-30.
6.
HungMCLauYK. Basic science of HER-2/neu: a review. Semin Oncol. 1999;26:51-59.
7.
YuDWangSSDulskiKMTsaiCMNicolsonGLHungMC. c-erbB-2/neu overexpression enhances metastatic potential of human lung cancer cells by induction of metastasis-associated properties. Cancer Res. 1994;54:3260-3266.
8.
OwensMAHortenBCDa SilvaMM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004;5:63-69.
9.
RossJSFletcherJABloomKJ. Targeted therapy in breast cancer: the HER-2/neu gene and protein. Mol Cell Proteomics. 2004;3:379-398.
10.
SlamonDJClarkGMWongSGLevinWJUllrichAMcGuireWL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177-182.
11.
SlamonDJGodolphinWJonesLA. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707-712.
12.
BorgATandonAKSigurdssonH. HER-2/neu amplification predicts poor survival in node-positive breast cancer. Cancer Res. 1990;50:4332-4337.
13.
DuffyMJ. Predictive markers in breast and other cancers: a review. Clin Chem. 2005;51:494-503.
14.
GustersonBAGelberRDGoldhirschA. Prognostic importance of c-erbB-2 expression in breast cancer: International (Ludwig) Breast Cancer Study Group. J Clin Oncol. 1992;10:1049-1056.
15.
PaikSParkC. HER-2 and choice of adjuvant chemotherapy in breast cancer. Semin Oncol. 2001;28:332-335.
16.
PritchardKIShepherdLEO’MalleyFP. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006;354:2103-2111.
17.
ThorADBerryDABudmanDR. erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst. 1998;90:1346-1360.
18.
PaulettiGGodolphinWPressMFSlamonDJ. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene. 1996;13:63-72.
19.
JoensuuHKellokumpu-LehtinenPLBonoP. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354:809-820.
20.
Piccart-GebhartMJProcterMLeyland-JonesB. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659-1672.
21.
RomondEHPerezEABryantJ. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673-1684.
22.
SlamonDJLeyland-JonesBShakS. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783-792.
23.
SmithIProcterMGelberRD. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007;369:29-36.
24.
VogelCLCobleighMATripathyD. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:719-726.
25.
BilousMDowsettMHannaW. Current perspectives on HER2 testing: a review of national testing guidelines. Mod Pathol. 2003;16:173-182.
26.
WolffACHammondMESchwartzJN. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118-145.
27.
PaikSBryantJTan-ChiuE. Real-world performance of HER2 testing: National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst. 2002;94:852-854.
28.
RochePCSumanVJJenkinsRB. Concordance between local and central laboratory HER2 testing in the breast intergroup trial N9831. J Natl Cancer Inst. 2002;94:855-857.
29.
HofmannMStossOGaiserT. Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy. J Clin Pathol. 2008;61:89-94.
30.
SalidoMTusquetsICorominasJM. Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry. Breast Cancer Res. 2005;7:R267-R273.
31.
TorrisiRRotmenszNBagnardiV. HER2 status in early breast cancer: relevance of cell staining patterns, gene amplification and polysomy 17. Eur J Cancer. 2007;43:2339-2344.
32.
AnbazhaganRGelberRDBettelheimRGoldhirschAGustersonBA. Association of c-erbB-2 expression and S-phase fraction in the prognosis of node positive breast cancer. Ann Oncol. 1991;2:47-53.
33.
KallioniemiOPHolliKVisakorpiTKoivulaTHelinHHIsolaJJ. Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer. 1991;49:650-655.
34.
LovekinCEllisIOLockerA. c-erbB-2 oncoprotein expression in primary and advanced breast cancer. Br J Cancer. 1991;63:439-443.
35.
McCannAHDervanPAO’ReganM. Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. Cancer Res. 1991;51:3296-3303.
36.
SelvarajanSWongKYKhooKSBayBHTanPH. Over-expression of c-erbB-2 correlates with nuclear morphometry and prognosis in breast carcinoma in Asian women. Pathology. 2006;38:528-533.
37.
PintoAEAndreSPereiraTNobregaSSoaresJ. C-erbB-2 oncoprotein overexpression identifies a subgroup of estrogen receptor positive (ER+) breast cancer patients with poor prognosis. Ann Oncol. 2001;12:525-533.
38.
BenzCCScottGKSarupJC. Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat. 1992;24:85-95.
39.
BorgABaldetorpBFernoMKillanderDOlssonHSigurdssonH. ERBB2 amplification in breast cancer with a high rate of proliferation. Oncogene. 1991;6:137-143.
40.
LiuYel-AshryDChenDDingIYKernFG. MCF-7 breast cancer cells overexpressing transfected c-erbB-2 have an in vitro growth advantage in estrogen-depleted conditions and reduced estrogen-dependence and tamoxifen-sensitivity in vivo. Breast Cancer Res Treat. 1995;34:97-117.
41.
BartlettJMGoingJJMallonEA. Evaluating HER2 amplification and overexpression in breast cancer. J Pathol. 2001;195:422-428.
42.
PerezEASumanVJDavidsonNE. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol. 2006;24:3032-3038.
43.
HyunCLLeeHEKimKS. The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer. J Clin Pathol. 2008;61:317-321.
44.
Vanden BemptIVan LooPDrijkoningenM. Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing. J Clin Oncol. 2008;26:4869-4874.
45.
BoseSMohammedMShintakuPRaoPN. Her-2/neu gene amplification in low to moderately expressing breast cancers: possible role of chromosome 17/Her-2/neu polysomy. Breast J. 2001;7:337-344.
46.
DohertyJKBondCJardimAAdelmanJPClintonGM. The HER-2/neu receptor tyrosine kinase gene encodes a secreted autoinhibitor. Proc Natl Acad Sci U S A. 1999;96:10869-10874.
47.
MassRDPressMFAndersonS. Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. Clin Breast Cancer. 2005;6:240-246.
48.
CobleighMAVogelCLTripathyD. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17:2639-2648.
