Clinicopathological Characteristics of Basal Type Breast Cancer in Triple-Negative Breast Cancer

Goro Kutomi, Tousei Ohmura, Yasuyo Suzuki, Hidekazu Kameshima, Hiroaki Shima, Tomoko Takamaru, Fukino Satomi, Seiko Otokozawa, Mitsuru Mori, Koichi Hirata

Department of Public Health, Sapporo Medical University, School of Medicine, Sapporo, Japan.
First Department of Surgery, Sapporo Medical University, School of Medicine, Sapporo, Japan.

DOI: 10.4236/jct.2012.325106                

Abstract

Background: Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor 2 (HER2) expression. Patients with TNBC derive no benefit from molecularly targeted treatments, such as endocrine therapy or trastuzumab, as they lack the appropriate targets for these drugs. TNBC is characterized by its biological aggressiveness and poor prognosis, and consists of two subtypes, basal and nonbasal. The purpose of our study is to differentiate the clinicopathological characteristics of the two subtypes. Methods: 367 patients with primary breast cancer were recruited from April 2004 to December 2010 at 1st Department of Surgery, Sapporo Medical University. ER, PgR, and HER2 status were evaluated in all cases. Moreover, we classified TNBC into basal, nonbasal subtypes on the basis of immunohistochemical staining of epidermal growth factor receptor (EGFR), cytokeratin (CK) 5/6. Basal type was defined as CK5/6-positive and/or EGFR-positive, and nonbasal type was defined as no expression of these two markers. Results: Breast cancer subtypes by molecular classification were Hormone receptor (HR)-positive/HER2-negative (61%), HR-positive/HER2-positive (10%), HR-negative/HER2-positive (14%), and HR-negative/HER2-negative (15%). There was no difference between the basal type and the nonbasal type in clinicopathological factors. But, the basal type was significantly associated with Ki67 labeling index (p=0.0002), p53 expression (p=0.047), and BRCA1 expression (p=0.03). Further, patients with the basal type TNBC showed a shorter overall survival (p=0.032) than did patients with the nonbasal type. Conclusion: Classification of TNBC subtypes by EGFR, CK5/6 is a very useful prognostic factor, and highlights the need for the development of an adequate new strategy for the basal type TNBC.

Keywords

Triple-Negative Breast Cancer; Basal Type; EGFR; CK5/6

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	F. Podo, L. Buydens, H. Degani, R. Hilhorst, E. Klipp, I. Gribbestad, et al., “Triple-Negative Breast Cancer: Present Challenges and New Perspectives,” Molecular Oncology, Vol. 4, No. 3, 2010, pp. 209-229.
[2]	Y. Yamamoto, M. Ibusuki, M. Nakano, T. Kawasoe, R. Hiki and H. Iwase, “Clinical Significance of Basal-Like Subtype in Triple-Negative Breast Cancer,” Breast Cancer, Vol. 16, No. 4, 2009, pp. 260-267.
[3]	T. Ruijter, J. Veeck, J. Hoon, M. Engeland and T. Tjan-Heijnen, “Characterristcs of Triple-Negative Breast Cancer,” Journal of Cancer Research and Clinical Oncology, Vol. 137, No. 2, 2011, pp. 183-192.
[4]	R. Rouzier, C. M. Perou, W. F. Symmans, N. Ibrahim, M. Cristofanili, K. Anderson, et al., “Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy,” Clinical Cancer Research, Vol. 11, No. 16, 2005, pp. 5678-5685.
[5]	J. Reis-Filho and A. Tutt, “Triple Negative Tumours: A Critical Review,” Histopathology, 52, 1, 2008, pp. 108-118.
[6]	W. Irvin, Jr. and L. Carey, “What Is Triple-Negative Breast Cancer?” European Journal of Cancer, Vol. 44, No. 18, 2008, pp. 2799-2805.
[7]	M. Laurentiis, D. Cianniello, R. Caputo, B. Stanzione, G. Arpino, S. Cinieri, et al., “Treatment of Triple Negative Breast Cancer (TNBC): Current Options and Future Perspectives,” Cancer Treatment Reviews, Vol. 36, Suppl. 3, 2010, pp. S80-S86.
[8]	O. Gluz, C. Liedtke, N. Gottschalk, L. Pusztai, U. Nitz and N. Harbeck, “Triple-Negative Breast Cancer-Current Status and Future Directions,” Annals of Surgical Oncology, Vol. 20, No. 12, 2009, pp. 1913-1927.
[9]	T. Sorlie, C. M. Perou and R. Tibshirani, “Gene Expression Patterns of Breast Carcinomas Distinguish Tumor Subclasses with Clinical Implications,” Proceedings of the National Academy of Sciences of the United States, Vol. 98, No. 19, 2001, pp. 10869-10874. doi:10.1073/pnas.191367098
[10]	E. Korshing, J. Packeisen and K. Agelopoulos, “Cytogenetic Alterations and Cytokeratin Expression Patterns in Breast Cancer: Integrating a New Model of Breast Differentiation into Cytogenetic Pathways of Breast Carcinogenesis,” Laboratory Investigation, Vol. 82, No. 11, 2002, p. 1525.
[11]	D. Abd EI-Rehim, B. Graham and S. Pinder, “High-Throughput Protein Expression Analysis Using Tissue Microarray Technology of a Large Well-Characterised Series Identifies Biologically Distinct Classes of Breast Cancer Confirming Recent cDNA Expression Analysis,” International Journal of Cancer, Vol. 116, No. 3, 2005, pp. 340-350. doi:10.1002/ijc.21004
[12]	Y. Yamamoto and H. Iwase, “Clinicopathological Features and Treatment Strategy for Triple-Negative Breast Cancer,” International Journal of Clinical Oncology, Vol. 15, No. 4, 2010, pp. 341-351. doi:10.1007/s10147-010-0106-1
[13]	R. Nishimura and N. Arima, “Is Triple Negative a Prognostic Facter in Breast Cancer?” Breast Cancer, Vol. 15, No. 4, 2008, pp. 303-308. doi:10.1007/s12282-008-0042-3
[14]	H. Iwase, J. Kurebayashi, H. Tsuda, T. Ohta, M. Kurosumi, T. Iwase, et al., “Clinicopathological Analyses of Triple Negative Breast Cancer Using Surveillance Data from the Registration Committee of the Japanese Breast Cancer Society,” Breast Cancer, Vol. 17, No. 2, 2010, pp. 118- 124. doi:10.1007/s12282-009-0113-0
[15]	C. Liedtke, C. Mazouni, K. Hess, F. Andre, T. Aordai, J. Mejia, et al., “Response to Neoadjuvant Therapy and Long-Term Survival in Patients with Triple-Negative Breast Cancer,” Journal of Clinical Oncology, Vol. 26, No. 19, 2008, pp. 1275-1281. doi:10.1200/JCO.2007.14.4147
[16]	M. C. Cheang, D. Voduc and C. Bajdik, “Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype,” Clinical Cancer Research, Vol. 14, No. 5, 2008, pp. 1368-1376. doi:10.1158/1078-0432.CCR-07-1658
[17]	S. J. Dawson, E. Provenzano and C. Caldas, “Triple Negative Breast Cancers: Clinical and Prognostic Implications,” European Journal of Cancer, Vol. 45, No. 1, 2009, pp. 27-40. doi:10.1016/S0959-8049(09)70013-9
[18]	T. Byrski, J. Gronwald and T. Huzarski, “Response to Neoadjuvant Chemotherapy in Women with BRCA1- Positive Breast Cancers,” Breast Cancer Research and Treatment, Vol. 108, No. 2, 2008, pp. 289-296. doi:10.1007/s10549-007-9600-1
[19]	N. Turner, A. Tutt and A. Ashworth, “Targeting the DNA Repair Defect of BRCA Tumours,” Current Opinion in Pharmacology, Vol. 5, No. 4, 2005, pp. 388-393. doi:10.1016/j.coph.2005.03.006
[20]	H. Farmer, N. McCabe and C. J. Lord, “Targeting the DNA Repair Defect in BRCA Mutant Cells as a Therapeutic Strategy,” Nature, Vol. 434, No. 7035, 2005, pp. 917-921. doi:10.1038/nature03445
[21]	P. Fong, D. Boss and T. Yap, “Inhibition of Poly (ADP-Ribose) Polymerase in Tumor from BRCA Mutation Carriers,” The New England Journal of Medicine, Vol. 361, No. 2, 2009, pp. 123-134. doi:10.1056/NEJMoa0900212