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Published in: Annals of Surgical Oncology 3/2012

01-03-2012 | Breast Oncology

Prognostic Value of Basal Phenotype in HER2-overexpressing Breast Cancer

Authors: Sanjay P. Bagaria, MD, Partha S. Ray, MD, Jinhua Wang, PhD, Luisa Kropcho, MD, Alice Chung, MD, Myung-Shin Sim, PhD, Jaime M. Shamonki, MD, Silvana Martino, DO, Xiaojiang Cui, PhD, Armando E. Giuliano, MD

Published in: Annals of Surgical Oncology | Issue 3/2012

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Abstract

Background

Primary breast cancers that overexpress human epidermal growth factor receptor 2 have variable biological features and clinical outcomes. A subgroup of HER2-overexpressing tumors that express basal-like immunohistochemical markers—the so-called basal-HER2+ subtype—is associated with poor prognosis. We investigated the clinical relevance of this basal-HER2+ subtype within HER2-overexpressing breast tumors.

Methods

Database review identified consecutive patients with HER2-overexpressing breast cancer. Archival tumor specimens from these patients were immunostained for estrogen receptor (ER), HER2, and basal cytokeratin (CK) expression, then subtyped as luminal-HER2+ (ER positive and basal CK negative), HER2+ (ER negative and basal CK negative), and basal-HER2+ (ER negative and basal CK positive). Subtypes were correlated with clinicopathologic features and overall survival.

Results

Immunohistochemical assessment of 131 HER2-overexpressing breast tumors identified 79 (60%) luminal-HER2+ tumors, 40 (31%) HER2+ tumors, and 12 (9%) basal-HER2+ tumors. There was no difference in the use of adjuvant trastuzumab and chemotherapy among patients with these subtypes. Five-year overall survival was 65% for patients with basal-HER2+ tumors versus 94% (P = 0.0035) and 96% (P = 0.0031) for patients with luminal-HER2+ and HER2+ tumors, respectively. The basal-HER2+ subtype was associated with the worst prognosis after adjusting for age, tumor size, lymph node status, and adjuvant treatment (hazard ratio 5.06, 95% confidence interval 1.1–23.2, P = 0.037).

Conclusions

The basal-HER2+ subtype highlights the heterogeneous biology of HER2-overexpressing breast cancer. The basal-HER2+ subtype is independently associated with poor survival and may provide insight into breast cancer cell response to anti-HER2 therapy.
Literature
1.
go back to reference Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRef Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.PubMedCrossRef
2.
go back to reference Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.PubMedCrossRef Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244(4905):707–12.PubMedCrossRef
3.
go back to reference Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.PubMedCrossRef Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.PubMedCrossRef
4.
go back to reference Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.PubMedCrossRef Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.PubMedCrossRef
5.
go back to reference Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol. 1999;26(4 Suppl 12):78–83.PubMed Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol. 1999;26(4 Suppl 12):78–83.PubMed
6.
go back to reference Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.PubMedCrossRef Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.PubMedCrossRef
7.
go back to reference van ‘t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.PubMedCrossRef van ‘t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.PubMedCrossRef
8.
go back to reference Blows FM, Driver KE, Schmidt MK, et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010;7:e1000279.PubMedCrossRef Blows FM, Driver KE, Schmidt MK, et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010;7:e1000279.PubMedCrossRef
9.
go back to reference Laakso M, Tanner M, Nilsson J, et al. Basoluminal carcinoma: a new biologically and prognostically distinct entity between basal and luminal breast cancer. Clin Cancer Res. 2006;12(14 Pt 1):4185–91.PubMedCrossRef Laakso M, Tanner M, Nilsson J, et al. Basoluminal carcinoma: a new biologically and prognostically distinct entity between basal and luminal breast cancer. Clin Cancer Res. 2006;12(14 Pt 1):4185–91.PubMedCrossRef
10.
go back to reference Liu H, Fan Q, Zhang Z, et al. Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone receptor-negative invasive breast cancers. Hum Pathol. 2008;39:167–74.PubMedCrossRef Liu H, Fan Q, Zhang Z, et al. Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone receptor-negative invasive breast cancers. Hum Pathol. 2008;39:167–74.PubMedCrossRef
11.
go back to reference Weigelt B, Horlings HM, Kreike B, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216:141–50.PubMedCrossRef Weigelt B, Horlings HM, Kreike B, et al. Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol. 2008;216:141–50.PubMedCrossRef
12.
go back to reference Wolff AC, Hammond ME, Schwartz JN, et al. 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;25:118–45.PubMedCrossRef Wolff AC, Hammond ME, Schwartz JN, et al. 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;25:118–45.PubMedCrossRef
13.
go back to reference McShane LM, Altman DG, Sauerbrei W, et al. REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat. 2006;100:229–35.PubMedCrossRef McShane LM, Altman DG, Sauerbrei W, et al. REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat. 2006;100:229–35.PubMedCrossRef
14.
go back to reference Yamauchi H, O’Neill A, Gelman R, et al. Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein. J Clin Oncol. 1997;15:2518–25.PubMed Yamauchi H, O’Neill A, Gelman R, et al. Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein. J Clin Oncol. 1997;15:2518–25.PubMed
15.
go back to reference Cheang MC, Chia SK, Voduc D, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.PubMedCrossRef Cheang MC, Chia SK, Voduc D, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.PubMedCrossRef
16.
go back to reference Guo S, Sonenshein GE. Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway. Mol Cell Biol. 2004;24:8681–90.PubMedCrossRef Guo S, Sonenshein GE. Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway. Mol Cell Biol. 2004;24:8681–90.PubMedCrossRef
17.
go back to reference Harris LN, You F, Schnitt SJ, et al. Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer. Clin Cancer Res. 2007;13:1198–207.PubMedCrossRef Harris LN, You F, Schnitt SJ, et al. Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer. Clin Cancer Res. 2007;13:1198–207.PubMedCrossRef
18.
go back to reference Tanner M, Kapanen AI, Junttila T, et al. Characterization of a novel cell line established from a patient with Herceptin-resistant breast cancer. Mol Cancer Ther. 2004;3:1585–92.PubMed Tanner M, Kapanen AI, Junttila T, et al. Characterization of a novel cell line established from a patient with Herceptin-resistant breast cancer. Mol Cancer Ther. 2004;3:1585–92.PubMed
19.
go back to reference Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castillo B, et al. Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin). Int J Oncol. 2010;37:669–78.PubMed Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castillo B, et al. Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin). Int J Oncol. 2010;37:669–78.PubMed
Metadata
Title
Prognostic Value of Basal Phenotype in HER2-overexpressing Breast Cancer
Authors
Sanjay P. Bagaria, MD
Partha S. Ray, MD
Jinhua Wang, PhD
Luisa Kropcho, MD
Alice Chung, MD
Myung-Shin Sim, PhD
Jaime M. Shamonki, MD
Silvana Martino, DO
Xiaojiang Cui, PhD
Armando E. Giuliano, MD
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 3/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2032-5

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