p53 Expression in Triple Negative Breast Carcinomas: Evidence of Age-Related and Racial Differences

Simone Davion, Megan Sullivan, Stephen Rohan, Kalliopi P. Siziopikou

Department of Pathology, Breast Pathology Section, Northwestern University Feinberg School of Medicine, Chicago, USA..

DOI: 10.4236/jct.2012.325084                

Abstract

Triple negative breast carcinomas (TNBC), are defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression. The majority of TNBC are “basal-like”, a group originally defined by studies of mRNA gene expression profiles, but increasingly defined in the clinic by using surrogate markers such as CK 5/6. However, not all TNBC are basal-like. It is postulated that these subcategories of TNBC have distinct underlying biologies that drive their ultimate behavior, and response to treatment, with important implications for designing appropriate targeted therapies. In this study we report that within our cohort of 197 TNBC, distinct groups were identified that varied by CK 5/6 and p53 expression based on age and race. We propose that awareness of CK5/6 and p53 expression in younger and AA TNBC patients may facilitate identifying patients with unique tumor subtypes and may lead to better use of targeted therapies in this group of aggressive breast cancers.

Keywords

Triple Negative Breast Cancer; p53; Race; Age

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	W. D. Foulkes, I. E. Smith and J. S. Reis-Filho, “Triple-Negative Breast Cancer,” The New England Journal of Medicine, Vol. 363, No. 20, 2010, pp. 1938-1948.doi:10.1056/NEJMra1001389
[2]	C. M. Perou, “Molecular Stratification of Triple-Negative Breast Cancers,” Oncologist, Vol. 16, Suppl. 1, 2011, pp. 61-70. doi:10.1634/theoncologist.2011-S1-61
[3]	C. M. Perou, T. Sorlie, M. B. Eisen, et al., “Molecular Portraits of Human Breast Tumours,” Nature, Vol. 406, No. 6797, 2000, pp. 747-752. doi:10.1038/35021093
[4]	K. A. Dookeran, J. J. Dignam, K. Ferrer, M. Sekosan, W. McCaskill-Stevens and S. Gehlert, “p53 as a Marker of Prognosis in African-American Women with Breast Cancer,” Annals of Surgical Oncology, Vol. 17, No. 5, 2010, pp. 1398-1405. doi:10.1245/s10434-009-0889-3
[5]	C. M. Perou, “Molecular Stratification of Triple-Negative Breast Cancers,” Oncologist, Vol. 15, Suppl. 5, 2010, pp. 39-48. doi:10.1634/theoncologist.2010-S5-39
[6]	E. A. Comen and M. Robson, “Poly (ADP-Ribose) Polymerase Inhibitors in Triple-Negative Breast Cancer,” Cancer, Vol. 16, No. 1, 2010, pp. 48-52.doi:10.1097/PPO.0b013e3181cf01eb
[7]	K. H. Vousden and D. P. Lane, “p53 in Health and Disease,” Nature Reviews, Vol. 8, No. 4, 2007, pp. 275-283.doi:10.1038/nrm2147
[8]	N. Turner, A. Tutt and A. Ashworth, “Hallmarks of ‘BRCAness’ in Sporadic Cancers,” Nature Reviews, Vol. 4, No. 10, 2004, pp. 814-819. doi:10.1038/nrc1457
[9]	T. Sorlie, C. M. Perou, R. Tibshirani, et al., “Gene Expression Patterns of Breast Carcinomas Distinguish Tumor Subclasses with Clinical Implications,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 19, 2001, pp. 10869-10874.doi:10.1073/pnas.191367098
[10]	Z. Jiang, R. Jones, J. C. Liu, et al., “RB1 and p53 at the Crossroad of EMT and Triple-Negative Breast Cancer,” Cell Cycle, Vol. 10, No. 10, 2011, pp. 1563-1570.doi:10.4161/cc.10.10.15703
[11]	E. Biganzoli, D. Coradini, F. Ambrogi, et al., “p53 Status Identifies Two Subgroups of Triple-Negative Breast Cancers with Distinct Biological Features,” Japanese Journal of Clinical Oncology, Vol. 41, No. 2, 2011, pp. 172-179. doi:10.1093/jjco/hyq227
[12]	B. Adamo and C. K. Anders, “Stratifying Triple-Negative Breast Cancer: Which Definition(s) to Use?” Breast Cancer Research, Vol. 13, No. 2, 2011, p. 105.doi:10.1186/bcr2852
[13]	K. P. Siziopikou and M. Cobleigh, “The Basal Subtype of Breast Carcinomas May Represent the Group of Breast Tumors That Could Benefit from EGFR-Targeted Therapies,” Breast, Vol. 16, No. 1, 2007, pp. 104-107.doi:10.1016/j.breast.2006.09.003
[14]	K. P. Siziopikou, D. C. Gingell, K. Proussaloglou, et al., “Basal Subtype and EGFR Expression in Breast Carcinomas, Evidence of Racial Differences,” Breast Cancer Research and Treatment, Vol. 100, Supp. 1, 2006, p. 141
[15]	L. A. Carey, C. M. Perou, C. A. Livasy, et al., “Race, Breast Cancer Subtypes, and Survival in the Carolina Breast Cancer Study,” Journal of the American Medical Association, Vol. 295, No. 21, 2006, pp. 2492-2502.doi:10.1001/jama.295.21.2492
[16]	M. van de Rijn, C. M. Perou, R. Tibshirani, et al., “Expression of Cytokeratins 17 and 5 Identifies a Group Of Breast Carcinomas with Poor Clinical Outcome,” American Journal of Pathology, Vol. 161, No. 6, 2002, pp. 1991-1996. doi:10.1016/S0002-9440(10)64476-8
[17]	K. F. Trivers, M. J. Lund, P. L. Porter, et al., “The Epidemiology of Triple-Negative Breast Cancer, including Race,” Cancer Causes & Control, Vol. 20, No. 7, 2009, pp. 1071-1082. doi:10.1007/s10552-009-9331-1
[18]	R. C. Millikan, B. Newman, C. K. Tse, et al., “Epidemiology of Basal-Like Breast Cancer,” Breast Cancer Research and Treatment, Vol. 109, No. 1, 2008, pp. 123-139. doi:10.1007/s10549-007-9632-6
[19]	J. D. Albano, E. Ward, A. Jemal, et al., “Cancer Mortality in the United States by Education Level and Race,” Journal of the National Cancer Institute, Vol. 99, No. 18, 2007, pp. 1384-1394. doi:10.1093/jnci/djm127
[20]	N. N. A. Howlader, M. Krapcho, N. Neyman, R. Aminou, W. Waldron, S. F. Altekruse, C. L. Kosary, J. Ruhl, Z. Tatalovich, H. Cho, A. Mariotto, M. P. Eisner, D. R. Lewis, H. S. Chen, E. J. Feuer, K. A. Cronin and B. K. Edwards, “SEER Cancer Statistics Review, 1975-2008, National Cancer Institute,” Bethesda, Based on November 2010 Seasonal Energy Efficiency Ratio Data Submission.
[21]	K. S. Albain, J. M. Unger, J. J. Crowley, C. A. Coltman, Jr. and D. L. Hershman, “Racial Disparities in Cancer Survival among Randomized Clinical Trials Patients of the Southwest Oncology Group,” Journal of the National Cancer Institute, Vol. 101, No. 14, 2009, pp. 984-992.doi:10.1093/jnci/djp175
[22]	C. K. Anders, D. S. Hsu, G. Broadwater, et al., “Young Age at Diagnosis Correlates with Worse Prognosis and Defines a Subset of Breast Cancers with Shared Patterns of Gene Expression,” Journal of Clinical Oncology, Vol. 26, No. 20, 2008, pp. 3324-3330.doi:10.1200/JCO.2007.14.2471
[23]	American Cancer Society, “Breast Cancer Facts & Figures 2009-2010,” American Cancer Society, Inc., Atlanta, 2009-2010.
[24]	N. Klauber-DeMore, “Tumor Biology of Breast Cancer in Young Women,” Breast Diseases, Vol. 23, 2005, pp. 9-15.
[25]	K. Oshima, Y. Naoi, K. Kishi, et al., “Gene Expression Signature of TP53 But Not Its Mutation Status Predicts Response to Sequential Paclitaxel and 5-FU/Epirubicin/Cyclophosphamide in Human Breast Cancer,” Cancer Letters, Vol. 307, No. 2, 2011, pp. 149-157.doi:10.1016/j.canlet.2011.03.027
[26]	P. D. Pharoah, N. E. Day and C. Caldas, “Somatic Mutations in the p53 Gene and Prognosis in Breast Cancer: A Meta-Analysis,” British Journal of Cancer, Vol. 80, No. 12, 1999, pp. 1968-1973.doi:10.1038/sj.bjc.6690628
[27]	L. D. Miller, J. Smeds, J. George, et al., “An Expression Signature for p53 Status in Human Breast Cancer Predicts Mutation Status, Transcriptional Effects, and Patient Survival,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 38, 2005, pp. 13550-13555. doi:10.1073/pnas.0506230102
[28]	B. T. Hennessy, A. M. Gonzalez-Angulo, K. Stemke-Hale, et al., “Characterization of a Naturally Occurring Breast Cancer Subset Enriched in Epithelial-to-Mesenchymal Transition and Stem Cell Characteristics,” Cancer Research, Vol. 69, No. 10, 2009, pp. 4116-4124.doi:10.1158/0008-5472.CAN-08-3441
[29]	Z. Jiang, T. Deng, R. Jones, et al., “Rb Deletion in Mouse Mammary Progenitors Induces Luminal-B or Basal-Like/ EMT Tumor Subtypes Depending on p53 Status,” Journal of Clinical Investigation, Vol. 120, No. 9, 2010, pp. 3296-3309. doi:10.1172/JCI41490