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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Nottingham Prognostic Index in Triple-Negative Breast Cancer: a reliable prognostic tool?

Authors: André Albergaria, Sara Ricardo, Fernanda Milanezi, Vítor Carneiro, Isabel Amendoeira, Daniella Vieira, Jorge Cameselle-Teijeiro, Fernando Schmitt

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a "triple-negative" phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication.

Methods

The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer.

Results

We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are equally important to stratify different survival outcomes in non-TNBC as in TNBC. We also showed that the NPI retains the ability to stratify and predict survival of TNBC patients.

Conclusion

The importance of this study relies on the need of prognostication improvements on TNBC, showing, at a clinical standpoint, that Nottingham Prognostic Index is as a truthful prognostic tool in TNBC.
Appendix
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Literature
1.
Badve S, Dabbs DJ, Schnitt SJ, Baehner FL, Decker T, Eusebi V, Fox SB, Ichihara S, Jacquemier J, Lakhani SR, et al: Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Mod Pathol. 2011, 24 (2): 157-167. 10.1038/modpathol.2010.200.CrossRefPubMed
2.
Rakha EA, Ellis IO: Triple-negative/basal-like breast cancer: review. Pathology. 2009, 41 (1): 40-47. 10.1080/00313020802563510.CrossRefPubMed
3.
Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO: Prognostic markers in triple-negative breast cancer. Cancer. 2007, 109 (1): 25-32. 10.1002/cncr.22381.CrossRefPubMed
4.
Weigelt B, Reis-Filho JS: Histological and molecular types of breast cancer: is there a unifying taxonomy?. Nat Rev Clin Oncol. 2009, 6 (12): 718-730. 10.1038/nrclinonc.2009.166.CrossRefPubMed
5.
Diaz LK, Cryns VL, Symmans WF, Sneige N: Triple negative breast carcinoma and the basal phenotype: from expression profiling to clinical practice. Adv Anat Pathol. 2007, 14 (6): 419-430. 10.1097/PAP.0b013e3181594733.CrossRefPubMed
6.
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al: Molecular portraits of human breast tumours. Nature. 2000, 406 (6797): 747-752. 10.1038/35021093.CrossRefPubMed
7.
Perou CM, Jeffrey SS, van de Rijn M, Rees CA, Eisen MB, Ross DT, Pergamenschikov A, Williams CF, Zhu SX, Lee JC, et al: Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci USA. 1999, 96 (16): 9212-9217. 10.1073/pnas.96.16.9212.CrossRefPubMedPubMedCentral
8.
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98 (19): 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral
9.
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, et al: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003, 100 (14): 8418-8423. 10.1073/pnas.0932692100.CrossRefPubMedPubMedCentral
10.
Brenton JD, Carey LA, Ahmed AA, Caldas C: Molecular classification and molecular forecasting of breast cancer: ready for clinical application?. J Clin Oncol. 2005, 23 (29): 7350-7360. 10.1200/JCO.2005.03.3845.CrossRefPubMed
11.
Reis-Filho JS, Tutt AN: Triple negative tumours: a critical review. Histopathology. 2008, 52 (1): 108-118.CrossRefPubMed
12.
Reis-Filho JS, Westbury C, Pierga JY: The impact of expression profiling on prognostic and predictive testing in breast cancer. J Clin Pathol. 2006, 59 (3): 225-231. 10.1136/jcp.2005.028324.CrossRefPubMedPubMedCentral
13.
Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, et al: The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006, 7: 96-10.1186/1471-2164-7-96.CrossRefPubMedPubMedCentral
14.
Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, Davies S, Fauron C, He X, Hu Z, et al: Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009, 27 (8): 1160-1167. 10.1200/JCO.2008.18.1370.CrossRefPubMedPubMedCentral
15.
Rakha EA, Reis-Filho JS, Ellis IO: Basal-like breast cancer: a critical review. J Clin Oncol. 2008, 26 (15): 2568-2581. 10.1200/JCO.2007.13.1748.CrossRefPubMed
16.
Gusterson BA, Ross DT, Heath VJ, Stein T: Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res. 2005, 7 (4): 143-148. 10.1186/bcr1041.CrossRefPubMedPubMedCentral
17.
Jones C, Mackay A, Grigoriadis A, Cossu A, Reis-Filho JS, Fulford L, Dexter T, Davies S, Bulmer K, Ford E, et al: Expression profiling of purified normal human luminal and myoepithelial breast cells: identification of novel prognostic markers for breast cancer. Cancer Res. 2004, 64 (9): 3037-3045. 10.1158/0008-5472.CAN-03-2028.CrossRefPubMed
18.
Lakhani SR, O'Hare MJ: The mammary myoepithelial cell--Cinderella or ugly sister?. Breast Cancer Res. 2001, 3 (1): 1-4. 10.1186/bcr260.CrossRefPubMed
19.
Nofech-Mozes S, Trudeau M, Kahn HK, Dent R, Rawlinson E, Sun P, Narod SA, Hanna WM: Patterns of recurrence in the basal and non-basal subtypes of triple-negative breast cancers. Breast Cancer Res Treat. 2009, 118 (1): 131-137. 10.1007/s10549-008-0295-8.CrossRefPubMed
20.
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 (4): 688-694. 10.1007/s00428-005-0010-7.CrossRefPubMed
21.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, Livasy C, Cowan D, Dressler L, et al: Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004, 10 (16): 5367-5374. 10.1158/1078-0432.CCR-04-0220.CrossRefPubMed
22.
Paredes J, Correia AL, Ribeiro AS, Albergaria A, Milanezi F, Schmitt FC: P-cadherin expression in breast cancer: a review. Breast Cancer Res. 2007, 9 (5): 214.-10.1186/bcr1774.CrossRefPubMedPubMedCentral
23.
Paredes J, Lopes N, Milanezi F, Schmitt FC: P-cadherin and cytokeratin 5: useful adjunct markers to distinguish basal-like ductal carcinomas in situ. Virchows Arch. 2007, 450 (1): 73-80. 10.1007/s00428-006-0334-y.CrossRefPubMed
24.
Savage K, Lambros MB, Robertson D, Jones RL, Jones C, Mackay A, James M, Hornick JL, Pereira EM, Milanezi F, et al: Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin Cancer Res. 2007, 13 (1): 90-101. 10.1158/1078-0432.CCR-06-1371.CrossRefPubMed
25.
Savage K, Leung S, Todd SK, Brown LA, Jones RL, Robertson D, James M, Parry S, Rodrigues Pinilla SM, Huntsman D, et al: Distribution and significance of caveolin 2 expression in normal breast and invasive breast cancer: an immunofluorescence and immunohistochemical analysis. Breast Cancer Res Treat. 2008, 110 (2): 245-256. 10.1007/s10549-007-9718-1.CrossRefPubMed
26.
Arnes JB, Brunet JS, Stefansson I, Begin LR, Wong N, Chappuis PO, Akslen LA, Foulkes WD: Placental cadherin and the basal epithelial phenotype of BRCA1-related breast cancer. Clin Cancer Res. 2005, 11 (11): 4003-4011. 10.1158/1078-0432.CCR-04-2064.CrossRefPubMed
27.
Sitterding SM, Wiseman WR, Schiller CL, Luan C, Chen F, Moyano JV, Watkin WG, Wiley EL, Cryns VL, Diaz LK: AlphaB-crystallin: a novel marker of invasive basal-like and metaplastic breast carcinomas. Ann Diagn Pathol. 2008, 12 (1): 33-40. 10.1016/j.anndiagpath.2007.02.004.CrossRefPubMed
28.
Paredes J, Albergaria A, Oliveira JT, Jeronimo C, Milanezi F, Schmitt FC: P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation. Clin Cancer Res. 2005, 11 (16): 5869-5877. 10.1158/1078-0432.CCR-05-0059.CrossRefPubMed
29.
Albergaria A, Ribeiro AS, Pinho S, Milanezi F, Carneiro V, Sousa B, Sousa S, Oliveira C, Machado JC, Seruca R, et al: ICI 182,780 induces P-cadherin overexpression in breast cancer cells through chromatin remodelling at the promoter level: a role for C/EBPα in CDH3 gene activation. Hum Mol Genet. 2010, 11 (13): 2554-2566.CrossRef
30.
Weigelt B, Mackay A, A'Hern R, Natrajan R, Tan DS, Dowsett M, Ashworth A, Reis-Filho JS: Breast cancer molecular profiling with single sample predictors: a retrospective analysis. Lancet Oncol. 2010, 11: 339-349. 10.1016/S1470-2045(10)70008-5.CrossRefPubMed
31.
Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM, Nielsen TO: Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008, 14 (5): 1368-1376. 10.1158/1078-0432.CCR-07-1658.CrossRefPubMed
32.
Fulford LG, Reis-Filho JS, Ryder K, Jones C, Gillett CE, Hanby A, Easton D, Lakhani SR: Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival. Breast Cancer Res. 2007, 9 (1): R4.-CrossRefPubMedPubMedCentral
33.
Rakha E, Ellis I, Reis-Filho J: Are triple-negative and basal-like breast cancer synonymous?. Clin Cancer Res. 2008, 14 (2): 618-author reply 618-619CrossRefPubMed
34.
Reis-Filho JS, Milanezi F, Steele D, Savage K, Simpson PT, Nesland JM, Pereira EM, Lakhani SR, Schmitt FC: Metaplastic breast carcinomas are basal-like tumours. Histopathology. 2006, 49 (1): 10-21. 10.1111/j.1365-2559.2006.02467.x.CrossRefPubMed
35.
Irvin WJ, Carey LA: What is triple-negative breast cancer?. Eur J Cancer. 2008, 44 (18): 2799-2805. 10.1016/j.ejca.2008.09.034.CrossRefPubMed
36.
Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ: Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res. 2007, 9 (5): R65-10.1186/bcr1771.CrossRefPubMedPubMedCentral
37.
Sotiriou C, Pusztai L: Gene-expression signatures in breast cancer. N Engl J Med. 2009, 360 (8): 790-800. 10.1056/NEJMra0801289.CrossRefPubMed
38.
Rakha EA, Elsheikh SE, Aleskandarany MA, Habashi HO, Green AR, Powe DG, El-Sayed ME, Benhasouna A, Brunet JS, Akslen LA, et al: Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes. Clin Cancer Res. 2009, 15 (7): 2302-2310. 10.1158/1078-0432.CCR-08-2132.CrossRefPubMed
39.
Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA: Pattern of metastatic spread in triple-negative breast cancer. Breast Cancer Res Treat. 2009, 115 (2): 423-428. 10.1007/s10549-008-0086-2.CrossRefPubMed
40.
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA: Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007, 13 (15): 4429-4434. 10.1158/1078-0432.CCR-06-3045.CrossRefPubMed
41.
Tischkowitz M, Brunet JS, Begin LR, Huntsman DG, Cheang MC, Akslen LA, Nielsen TO, Foulkes WD: Use of immunohistochemical markers can refine prognosis in triple negative breast cancer. BMC Cancer. 2007, 7: 134-10.1186/1471-2407-7-134.CrossRefPubMedPubMedCentral
42.
Hicks DG, Short SM, Prescott NL, Tarr SM, Coleman KA, Yoder BJ, Crowe JP, Choueiri TK, Dawson AE, Budd GT, et al: Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR. Am J Surg Pathol. 2006, 30 (9): 1097-1104.CrossRefPubMed
43.
Rodriguez-Pinilla SM, Sarrio D, Honrado E, Hardisson D, Calero F, Benitez J, Palacios J: Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas. Clin Cancer Res. 2006, 12 (5): 1533-1539. 10.1158/1078-0432.CCR-05-2281.CrossRefPubMed
44.
Tsuda H, Takarabe T, Hasegawa T, Murata T, Hirohashi S: Myoepithelial differentiation in high-grade invasive ductal carcinomas with large central acellular zones. Hum Pathol. 1999, 30 (10): 1134-1139. 10.1016/S0046-8177(99)90028-X.CrossRefPubMed
45.
Lee AH, Ellis IO: The Nottingham prognostic index for invasive carcinoma of the breast. Pathol Oncol Res. 2008, 14 (2): 113-115. 10.1007/s12253-008-9067-3.CrossRefPubMed
46.
Miller DV, Leontovich AA, Lingle WL, Suman VJ, Mertens ML, Lillie J, Ingalls KA, Perez EA, Ingle JN, Couch FJ, et al: Utilizing Nottingham Prognostic Index in microarray gene expression profiling of breast carcinomas. Mod Pathol. 2004, 17 (7): 756-764. 10.1038/modpathol.3800114.CrossRefPubMed
47.
Galea MH, Blamey RW, Elston CE, Ellis IO: The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat. 1992, 22 (3): 207-219. 10.1007/BF01840834.CrossRefPubMed
48.
Kollias J, Murphy CA, Elston CW, Ellis IO, Robertson JF, Blamey RW: The prognosis of small primary breast cancers. Eur J Cancer. 1999, 35 (6): 908-912. 10.1016/S0959-8049(99)00056-8.CrossRefPubMed
49.
Sousa B, Paredes J, Milanezi F, Lopes N, Martins D, Dufloth R, Vieira D, Albergaria A, Veronese L, Carneiro V, et al: P-cadherin, vimentin and CK14 for identification of basal-like phenotype in breast carcinomas: an immunohistochemical study. Histol Histopathol. 2010, 25 (8): 963-974.PubMed
50.
Yang XR, Sherman ME, Rimm DL, Lissowska J, Brinton LA, Peplonska B, Hewitt SM, Anderson WF, Szeszenia-Dabrowska N, Bardin-Mikolajczak A, et al: Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev. 2007, 16 (3): 439-443. 10.1158/1055-9965.EPI-06-0806.CrossRefPubMed
51.
Dent R, Hanna WM, Trudeau M, Rawlinson E, Sun P, Narod SA: Time to disease recurrence in basal-type breast cancers: effects of tumor size and lymph node status. Cancer. 2009, 115 (21): 4917-4923. 10.1002/cncr.24573.CrossRefPubMed
52.
Foulkes WD, Smith IE, Reis-Filho JS: Triple-negative breast cancer. N Engl J Med. 2010, 363 (20): 1938-1948. 10.1056/NEJMra1001389.CrossRefPubMed
53.
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 (9): 1721-1728. 10.1002/cncr.22618.CrossRefPubMed
54.
Blows FM, Driver KE, Schmidt MK, Broeks A, van Leeuwen FE, Wesseling J, Cheang MC, Gelmon K, Nielsen TO, Blomqvist C, 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 (5): e1000279-10.1371/journal.pmed.1000279.CrossRefPubMedPubMedCentral
55.
Spitale A, Mazzola P, Soldini D, Mazzucchelli L, Bordoni A: Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Ann Oncol. 2009, 20 (4): 628-635. 10.1093/annonc/mdn675.CrossRefPubMed
56.
Foulkes WD, Grainge MJ, Rakha EA, Green AR, Ellis IO: Tumor size is an unreliable predictor of prognosis in basal-like breast cancers and does not correlate closely with lymph node status. Breast Cancer Res Treat. 2008, 117 (1): 199-204.CrossRefPubMed
Metadata
Title
Nottingham Prognostic Index in Triple-Negative Breast Cancer: a reliable prognostic tool?
Authors
André Albergaria
Sara Ricardo
Fernanda Milanezi
Vítor Carneiro
Isabel Amendoeira
Daniella Vieira
Jorge Cameselle-Teijeiro
Fernando Schmitt
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-299

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