Skip to main content
Top
Published in: Breast Cancer 4/2009

01-10-2009 | Conference Paper

Clinical significance of basal-like subtype in triple-negative breast cancer

Authors: Yutaka Yamamoto, Mutsuko Ibusuki, Masahiro Nakano, Teru Kawasoe, Ryousuke Hiki, Hirotaka Iwase

Published in: Breast Cancer | Issue 4/2009

Login to get access

Abstract

Background

No clinically useful target molecule has been identified for triple-negative (TN) breast cancer, i.e., estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, human epidermal growth factor receptor-2 (HER2)-negative phenotype, and its prognosis is poor. Triple-negative cancer consists of two subtypes: basal-like and non-basal-like. The aim of this study is to clarify the clinical and biological characteristics of these two subtypes of TN cancer.

Methods

We examined, by immunohistochemistry, expression of biological markers cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) in triple-negative breast cancer. Basal-like subtype was defined as CK5/6-positive and/or EGFR-positive, and non-basal-like subtype was defined as no expression of these two markers. We studied the correlation between basal-like subtype and several factors related to tumor progression, along with the prognostic value of basal-like subtype and other biological markers in triple-negative cancer.

Results

In the 48 cases of operable triple-negative breast cancer, basal-like subtype was detected in 22 (45.8%) and non-basal-like subtype in 26 (54.2%). Basal-like subtype was significantly correlated with nodal status (P = 0.0475) and nuclear grade (P = 0.0475). Basal-like subtype was also significantly associated with Ki67 labeling index (P = 0.0118), c-kit expression (P = 0.0335), and aurora A expression (P = 0.0020). No association was detected between basal-like cancer and other biological markers. Patients with basal-like subtype of triple-negative cancer showed shorter disease-free survival (P = 0.0049) and overall survival (P = 0.0283) than patients with non-basal-like subtype. No independent prognostic factors were identified among the prognostic factors obtained from univariate analysis.

Conclusions

These findings suggest that basal markers can be used to classify triple-negative breast cancer into at least two subtypes with differing prognoses. It is necessary to develop a novel treatment strategy to improve the prognosis of patients with basal-like subtype of triple-negative breast cancer.
Literature
1.
go back to reference Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.PubMedCrossRef Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.PubMedCrossRef
2.
go back to reference Konecny G, Pauletti G, Pegram M, Untch M, Dandekar S, Aguila Z, et al. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst. 2003;95:142–53.PubMedCrossRef Konecny G, Pauletti G, Pegram M, Untch M, Dandekar S, Aguila Z, et al. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst. 2003;95:142–53.PubMedCrossRef
3.
go back to reference Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12.PubMedCrossRef Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989;244:707–12.PubMedCrossRef
4.
go back to reference Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.PubMedCrossRef Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.PubMedCrossRef
5.
go back to reference Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.PubMedCrossRef Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.PubMedCrossRef
6.
go back to reference Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006;24:5652–7.PubMedCrossRef Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol. 2006;24:5652–7.PubMedCrossRef
7.
go back to reference Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32.PubMedCrossRef Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32.PubMedCrossRef
8.
go back to reference Tischkowitz M, Brunet JS, Begin LR, Huntsman DG, Cheang MC, Akslen LA, et al. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer. 2007;7:134.PubMedCrossRef Tischkowitz M, Brunet JS, Begin LR, Huntsman DG, Cheang MC, Akslen LA, et al. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer. 2007;7:134.PubMedCrossRef
9.
go back to reference Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109:1721–8.PubMedCrossRef Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109:1721–8.PubMedCrossRef
10.
go back to reference Harris LN, Broadwater G, Lin NU, Miron A, Schnitt SJ, Cowan D, et al. Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342. Breast Cancer Res. 2006;8:R66.PubMedCrossRef Harris LN, Broadwater G, Lin NU, Miron A, Schnitt SJ, Cowan D, et al. Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342. Breast Cancer Res. 2006;8:R66.PubMedCrossRef
11.
go back to reference Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P, et al. Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Cancer. 2007;110:876–84.PubMedCrossRef Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P, et al. Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Cancer. 2007;110:876–84.PubMedCrossRef
12.
go back to reference Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8:235–44.PubMedCrossRef Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8:235–44.PubMedCrossRef
13.
go back to reference Reis-Filho JS, Tutt AN. Triple negative tumours: a critical review. Histopathology. 2008;52:108–18.PubMedCrossRef Reis-Filho JS, Tutt AN. Triple negative tumours: a critical review. Histopathology. 2008;52:108–18.PubMedCrossRef
14.
go back to reference Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRef
15.
go back to reference Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.PubMedCrossRef Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.PubMedCrossRef
16.
go back to reference Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.PubMedCrossRef Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.PubMedCrossRef
17.
go back to reference van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol. 2002;161:1991–6.PubMed van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol. 2002;161:1991–6.PubMed
18.
go back to reference Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F. p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch. 2005;447:688–94.PubMedCrossRef Matos I, Dufloth R, Alvarenga M, Zeferino LC, Schmitt F. p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch. 2005;447:688–94.PubMedCrossRef
19.
go back to reference Kobayashi S. Basal-like subtype of breast cancer: a review of its unique characteristics and their clinical significance. Breast Cancer. 2008;15:153–8.PubMedCrossRef Kobayashi S. Basal-like subtype of breast cancer: a review of its unique characteristics and their clinical significance. Breast Cancer. 2008;15:153–8.PubMedCrossRef
20.
go back to reference Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85.PubMedCrossRef Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85.PubMedCrossRef
21.
go back to reference Bidard FC, Conforti R, Boulet T, Michiels S, Delaloge S. Andre F.egative phenotype accurately identify basal-like tumour? An immunohistochemical analysis based on 143 ‘triple-negative’ breast cancers. Ann Oncol. 2007;18:1285–6.PubMedCrossRef Bidard FC, Conforti R, Boulet T, Michiels S, Delaloge S. Andre F.egative phenotype accurately identify basal-like tumour? An immunohistochemical analysis based on 143 ‘triple-negative’ breast cancers. Ann Oncol. 2007;18:1285–6.PubMedCrossRef
22.
go back to reference Tan DS, Marchio C, Jones RL, Savage K, Smith IE, Dowsett M, et al. Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients. Breast Cancer Res Treat. 2008;111:27–44.PubMedCrossRef Tan DS, Marchio C, Jones RL, Savage K, Smith IE, Dowsett M, et al. Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients. Breast Cancer Res Treat. 2008;111:27–44.PubMedCrossRef
23.
go back to reference Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14:1368–76.PubMedCrossRef Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14:1368–76.PubMedCrossRef
24.
go back to reference Sasa M, Bando Y, Takahashi M, Hirose T, Nagao T. Screening for basal marker expression is necessary for decision of therapeutic strategy for triple-negative breast cancer. J Surg Oncol. 2008;97:30–4.PubMedCrossRef Sasa M, Bando Y, Takahashi M, Hirose T, Nagao T. Screening for basal marker expression is necessary for decision of therapeutic strategy for triple-negative breast cancer. J Surg Oncol. 2008;97:30–4.PubMedCrossRef
25.
go back to reference Yamamoto Y, Ibusuki M, Okumura Y, Kawasoe T, Kai K, Iyama K, et al. Hypoxia-inducible factor 1alpha is closely linked to an aggressive phenotype in breast cancer. Breast Cancer Res Treat. 2008;110:465–75.PubMedCrossRef Yamamoto Y, Ibusuki M, Okumura Y, Kawasoe T, Kai K, Iyama K, et al. Hypoxia-inducible factor 1alpha is closely linked to an aggressive phenotype in breast cancer. Breast Cancer Res Treat. 2008;110:465–75.PubMedCrossRef
26.
go back to reference Bos R, van der Groep P, Greijer AE, Shavarts A, Meijer S, Pinedo HM, et al. Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer. 2003;97:1573–81.PubMedCrossRef Bos R, van der Groep P, Greijer AE, Shavarts A, Meijer S, Pinedo HM, et al. Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer. 2003;97:1573–81.PubMedCrossRef
27.
go back to reference Royce ME, Xia W, Sahin AA, Katayama H, Johnston DA, Hortobagi G, et al. STK15/Aurora-A expression in primary breast tumors is correlated with nuclear grade but not with prognosis. Cancer. 2003;100:12–9.CrossRef Royce ME, Xia W, Sahin AA, Katayama H, Johnston DA, Hortobagi G, et al. STK15/Aurora-A expression in primary breast tumors is correlated with nuclear grade but not with prognosis. Cancer. 2003;100:12–9.CrossRef
28.
go back to reference Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol. 2003;21:3357–65.PubMedCrossRef Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol. 2003;21:3357–65.PubMedCrossRef
29.
go back to reference Spyratos F, Ferrero-Pous M, Trassard M, Hacene K, Phillips E, Tubiana-Hulin M, et al. Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value. Cancer. 2002;94:2151–9.PubMedCrossRef Spyratos F, Ferrero-Pous M, Trassard M, Hacene K, Phillips E, Tubiana-Hulin M, et al. Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value. Cancer. 2002;94:2151–9.PubMedCrossRef
30.
go back to reference Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.PubMedCrossRef Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.PubMedCrossRef
31.
go back to reference Natali PG, Nicotra MR, Sures I, Mottolese M, Botti C, Ullrich A. Breast cancer is associated with loss of the c-kit oncogene product. Int J Cancer. 1992;52:713–7.PubMedCrossRef Natali PG, Nicotra MR, Sures I, Mottolese M, Botti C, Ullrich A. Breast cancer is associated with loss of the c-kit oncogene product. Int J Cancer. 1992;52:713–7.PubMedCrossRef
32.
go back to reference Chui X, Egami H, Yamashita J, Kurizaki T, Ohmachi H, Yamamoto S, et al. Immunohistochemical expression of the c-kit proto-oncogene product in human malignant and non-malignant breast tissues. Br J Cancer. 1996;73:1233–6.PubMed Chui X, Egami H, Yamashita J, Kurizaki T, Ohmachi H, Yamamoto S, et al. Immunohistochemical expression of the c-kit proto-oncogene product in human malignant and non-malignant breast tissues. Br J Cancer. 1996;73:1233–6.PubMed
33.
go back to reference Gautschi O, Heighway J, Mack PC, Purnell PR, Lara PN, Gandara DR Jr. Aurora kinases as anticancer drug targets. Clin Cancer Res. 2008;14:1639–48.PubMedCrossRef Gautschi O, Heighway J, Mack PC, Purnell PR, Lara PN, Gandara DR Jr. Aurora kinases as anticancer drug targets. Clin Cancer Res. 2008;14:1639–48.PubMedCrossRef
34.
go back to reference Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 1998;17:3052–65.PubMedCrossRef Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 1998;17:3052–65.PubMedCrossRef
35.
go back to reference Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet. 1998;20:189–93.PubMedCrossRef Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet. 1998;20:189–93.PubMedCrossRef
36.
go back to reference Nadler Y, Camp RL, Schwartz C, Rimm DL, Kluger HM, Kluger Y. Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer. Clin Cancer Res. 2008;14:4455–62.PubMedCrossRef Nadler Y, Camp RL, Schwartz C, Rimm DL, Kluger HM, Kluger Y. Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer. Clin Cancer Res. 2008;14:4455–62.PubMedCrossRef
Metadata
Title
Clinical significance of basal-like subtype in triple-negative breast cancer
Authors
Yutaka Yamamoto
Mutsuko Ibusuki
Masahiro Nakano
Teru Kawasoe
Ryousuke Hiki
Hirotaka Iwase
Publication date
01-10-2009
Publisher
Springer Japan
Published in
Breast Cancer / Issue 4/2009
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-009-0150-8

Other articles of this Issue 4/2009

Breast Cancer 4/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine