This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foulkes, W. D. Articles by Akslen, L. A. Search for Related Content PubMed PubMed Citation Articles by Foulkes, W. D. Articles by Akslen, L. A.

The Prognostic Implication of the Basal-Like (Cyclin E^high/p27^low/p53⁺/Glomeruloid-Microvascular-Proliferation⁺) Phenotype of BRCA1-Related Breast Cancer

¹ Program in Cancer Genetics and Departments of ² Oncology, ³ Human Genetics, ⁴ Medicine, ⁵ Surgery, and ⁶ Pathology, ⁷ Research Institute of the McGill University Health Centre, and ⁸ Cancer Prevention Centre, Sir M. B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; ⁹ Algorithme Pharma, Montreal, Quebec, Canada; ¹⁰ Department of Pathology, The Gade Institute, Haukeland University Hospital, Bergen, Norway; ¹¹ Department of Pathology, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; and ¹² Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center and Department of Pathology, University of Washington, Seattle, Washington

Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27^Kip1, or cyclin D1, but do express p53 and cyclin E. In addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27^Kip1, p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27^Kip1 levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.

This article has been cited by other articles:

				O. Gluz, C. Liedtke, N. Gottschalk, L. Pusztai, U. Nitz, and N. Harbeck Triple-negative breast cancer--current status and future directions Ann. Onc., December 1, 2009; 20(12): 1913 - 1927. [Abstract] [Full Text] [PDF]

				P van der Groep, P J van Diest, F H Menko, J Bart, E G E de Vries, and E van der Wall Molecular profile of ductal carcinoma in situ of the breast in BRCA1 and BRCA2 germline mutation carriers J. Clin. Pathol., October 1, 2009; 62(10): 926 - 930. [Abstract] [Full Text] [PDF]

				M. Filipits, M. Rudas, H. Heinzl, R. Jakesz, E. Kubista, S. Lax, W. Schippinger, O. Dietze, R. Greil, W. Stiglbauer, et al. Low p27 Expression Predicts Early Relapse and Death in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients Receiving Adjuvant Tamoxifen Therapy Clin. Cancer Res., September 15, 2009; 15(18): 5888 - 5894. [Abstract] [Full Text] [PDF]

				J. Ding, G. He, W. Gong, W. Wen, W. Sun, B. Ning, S. Huang, K. Wu, C. Huang, M. Wu, et al. Effects of Nickel on Cyclin Expression, Cell Cycle Progression and Cell Proliferation in Human Pulmonary Cells Cancer Epidemiol. Biomarkers Prev., June 1, 2009; 18(6): 1720 - 1729. [Abstract] [Full Text] [PDF]

				B. Corkery, J. Crown, M. Clynes, and N. O'Donovan Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer Ann. Onc., May 1, 2009; 20(5): 862 - 867. [Abstract] [Full Text] [PDF]

				J. Fasano and F. Muggia Breast cancer arising in a BRCA-mutated background: therapeutic implications from an animal model and drug development Ann. Onc., April 1, 2009; 20(4): 609 - 614. [Abstract] [Full Text] [PDF]

				E. A. Rakha, S. E. Elsheikh, M. A. Aleskandarany, H. O. Habashi, A. R. Green, D. G. Powe, M. E. El-Sayed, A. Benhasouna, J.-S. Brunet, L. A. Akslen, et al. Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes Clin. Cancer Res., April 1, 2009; 15(7): 2302 - 2310. [Abstract] [Full Text] [PDF]

				C. Sotiriou and L. Pusztai Gene-Expression Signatures in Breast Cancer N. Engl. J. Med., February 19, 2009; 360(8): 790 - 800. [Full Text] [PDF]

				J B Arnes, L R Begin, I Stefansson, J-S Brunet, T O Nielsen, W D Foulkes, and L A Akslen Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer J. Clin. Pathol., February 1, 2009; 62(2): 139 - 146. [Abstract] [Full Text] [PDF]

				B. P. Schneider, E. P. Winer, W. D. Foulkes, J. Garber, C. M. Perou, A. Richardson, G. W. Sledge, and L. A. Carey Triple-Negative Breast Cancer: Risk Factors to Potential Targets Clin. Cancer Res., December 15, 2008; 14(24): 8010 - 8018. [Abstract] [Full Text] [PDF]

				D. P. Atchley, C. T. Albarracin, A. Lopez, V. Valero, C. I. Amos, A. M. Gonzalez-Angulo, G. N. Hortobagyi, and B. K. Arun Clinical and Pathologic Characteristics of Patients With BRCA-Positive and BRCA-Negative Breast Cancer J. Clin. Oncol., September 10, 2008; 26(26): 4282 - 4288. [Abstract] [Full Text] [PDF]

				A. A. Luck, A. J. Evans, J. J. James, E. A. Rakha, E. C. Paish, A. R. Green, and I. O. Ellis Breast Carcinoma with Basal Phenotype: Mammographic Findings Am. J. Roentgenol., August 1, 2008; 191(2): 346 - 351. [Abstract] [Full Text] [PDF]

				F.-C. Bidard, M.-C. Matthieu, P. Chollet, I. Raoefils, C. Abrial, J. Domont, M. Spielmann, S. Delaloge, F. Andre, and F. Penault-Llorca p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen according to breast cancer molecular classes Ann. Onc., July 1, 2008; 19(7): 1261 - 1265. [Abstract] [Full Text] [PDF]

				E. A. Rakha, J. S. Reis-Filho, and I. O. Ellis Basal-Like Breast Cancer: A Critical Review J. Clin. Oncol., May 20, 2008; 26(15): 2568 - 2581. [Abstract] [Full Text] [PDF]

				A. B. Spurdle, S. R. Lakhani, S. Healey, S. Parry, L. M. Da Silva, R. Brinkworth, J. L. Hopper, M. A. Brown, D. Babikyan, G. Chenevix-Trench, et al. Clinical Classification of BRCA1 and BRCA2 DNA Sequence Variants: The Value of Cytokeratin Profiles and Evolutionary Analysis--A Report From the kConFab Investigators J. Clin. Oncol., April 1, 2008; 26(10): 1657 - 1663. [Abstract] [Full Text] [PDF]

				K. Aaltonen, C. Blomqvist, R.-M. Amini, H. Eerola, K. Aittomaki, P. Heikkila, and H. Nevanlinna Familial Breast Cancers without Mutations in BRCA1 or BRCA2 Have Low Cyclin E and High Cyclin D1 in Contrast to Cancers in BRCA Mutation Carriers Clin. Cancer Res., April 1, 2008; 14(7): 1976 - 1983. [Abstract] [Full Text] [PDF]

				E. J. Wasserman and A. R. Tan Evolving Strategies for the Treatment of "Triple-Negative" Breast Cancer ASCO Educational Book, January 1, 2008; 2008(1): 120 - 126. [Abstract] [Full Text] [PDF]

				S. M. Rodriguez-Pinilla, D. Sarrio, E. Honrado, G. Moreno-Bueno, D. Hardisson, F. Calero, J. Benitez, and J. Palacios Vimentin and laminin expression is associated with basal-like phenotype in both sporadic and BRCA1-associated breast carcinomas J. Clin. Pathol., September 1, 2007; 60(9): 1006 - 1012. [Abstract] [Full Text] [PDF]

				R. Dent, M. Trudeau, K. I. Pritchard, W. M. Hanna, H. K. Kahn, C. A. Sawka, L. A. Lickley, E. Rawlinson, P. Sun, and S. A. Narod Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence Clin. Cancer Res., August 1, 2007; 13(15): 4429 - 4434. [Abstract] [Full Text] [PDF]

				S. A. Mani, J. Yang, M. Brooks, G. Schwaninger, A. Zhou, N. Miura, J. L. Kutok, K. Hartwell, A. L. Richardson, and R. A. Weinberg Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers PNAS, June 12, 2007; 104(24): 10069 - 10074. [Abstract] [Full Text] [PDF]

				C. R. James, J. E. Quinn, P. B. Mullan, P. G. Johnston, and D. P. Harkin BRCA1, a Potential Predictive Biomarker in the Treatment of Breast Cancer Oncologist, February 1, 2007; 12(2): 142 - 150. [Abstract] [Full Text] [PDF]

				M. Dolled-Filhart, L. Ryden, M. Cregger, K. Jirstrom, M. Harigopal, R. L. Camp, and D. L. Rimm Classification of breast cancer using genetic algorithms and tissue microarrays. Clin. Cancer Res., November 1, 2006; 12(21): 6459 - 6468. [Abstract] [Full Text] [PDF]

				L. A. Carey, C. M. Perou, C. A. Livasy, L. G. Dressler, D. Cowan, K. Conway, G. Karaca, M. A. Troester, C. K. Tse, S. Edmiston, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA, June 7, 2006; 295(21): 2492 - 2502. [Abstract] [Full Text] [PDF]

				P van der Groep, A Bouter, R van der Zanden, I Siccama, F H Menko, J J P Gille, C van Kalken, E van der Wall, R H M Verheijen, and P J van Diest Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data J. Clin. Pathol., June 1, 2006; 59(6): 611 - 617. [Abstract] [Full Text] [PDF]

				P. Potemski, E. Pluciennik, A. K. Bednarek, R. Kusinska, D. Jesionek-Kupnicka, G. Pasz-Walczak, C. Watala, and R. Kordek Cyclin E Expression in Operable Breast Cancer Quantified Using Real-Time RT-PCR: A Comparative Study with Immunostaining Jpn. J. Clin. Oncol., March 1, 2006; 36(3): 142 - 149. [Abstract] [Full Text] [PDF]

				S. M. Rodriguez-Pinilla, D. Sarrio, E. Honrado, D. Hardisson, F. Calero, J. Benitez, and J. Palacios Prognostic Significance of Basal-Like Phenotype and Fascin Expression in Node-Negative Invasive Breast Carcinomas Clin. Cancer Res., March 1, 2006; 12(5): 1533 - 1539. [Abstract] [Full Text] [PDF]

				K. Collett, G. E. Eide, J. Arnes, I. M. Stefansson, J. Eide, A. Braaten, T. Aas, A. P. Otte, and L. A. Akslen Expression of Enhancer of Zeste Homologue 2 Is Significantly Associated with Increased Tumor Cell Proliferation and Is a Marker of Aggressive Breast Cancer Clin. Cancer Res., February 15, 2006; 12(4): 1168 - 1174. [Abstract] [Full Text] [PDF]

				W F Symmans, D J Fiterman, S K Anderson, M Ayers, R Rouzier, V Dunmire, J Stec, V Valero, N Sneige, C Albarracin, et al. A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding Endocr. Relat. Cancer, December 1, 2005; 12(4): 1059 - 1069. [Abstract] [Full Text] [PDF]

				M. Colozza, E. Azambuja, F. Cardoso, C. Sotiriou, D. Larsimont, and M. J. Piccart Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann. Onc., November 1, 2005; 16(11): 1723 - 1739. [Abstract] [Full Text] [PDF]

				A. Goldhirsch, J. H. Glick, R. D. Gelber, A. S. Coates, B. Thurlimann, H.-J. Senn, and and Panel Members Meeting Highlights: International Expert Consensus on the Primary Therapy of Early Breast Cancer 2005 Ann. Onc., October 1, 2005; 16(10): 1569 - 1583. [Abstract] [Full Text] [PDF]

				J. B. Arnes, J.-S. Brunet, I. Stefansson, L. R. Begin, N. Wong, P. O. Chappuis, L. A. Akslen, and W. D. Foulkes Placental Cadherin and the Basal Epithelial Phenotype of BRCA1-Related Breast Cancer Clin. Cancer Res., June 1, 2005; 11(11): 4003 - 4011. [Abstract] [Full Text] [PDF]

				P. O. Chappuis, E. Donato, J. R. Goffin, N. Wong, L. R. Begin, L. R. Kapusta, J.-S. Brunet, P. Porter, and W. D. Foulkes Cyclin E expression in breast cancer: predicting germline BRCA1 mutations, prognosis and response to treatment Ann. Onc., May 1, 2005; 16(5): 735 - 742. [Abstract] [Full Text] [PDF]

				S. GANESAN, A.L. RICHARDSON, Z.C. WANG, J.D. IGLEHART, A. MIRON, J. FEUNTEUN, D. SILVER, and D.M. LIVINGSTON Abnormalities of the Inactive X Chromosome Are a Common Feature of BRCA1 Mutant and Sporadic Basal-like Breast Cancer Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 93 - 97. [Abstract] [PDF]

				V. Venkateswaran, N. E. Fleshner, L. M. Sugar, and L. H. Klotz Antioxidants Block Prostate Cancer in Lady Transgenic Mice Cancer Res., August 15, 2004; 64(16): 5891 - 5896. [Abstract] [Full Text] [PDF]