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Breast Cancer Research
Published in: Breast Cancer Research 1/2007

Open Access 01-02-2007 | Research article

Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival

Authors: Laura G Fulford, Jorge S Reis-Filho, Ken Ryder, Chris Jones, Cheryl E Gillett, Andrew Hanby, Douglas Easton, Sunil R Lakhani

Published in: Breast Cancer Research | Issue 1/2007

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Abstract

Introduction

Cytokeratin (CK) 14, one of several markers expressed in normal myoepithelial/basal cells, is also expressed in a proportion of breast carcinomas. Previous studies have suggested that expression of such 'basal' markers predicts different biological behaviour, with more frequent lung and brain metastases and poorer prognosis than other carcinomas.

Methods

We performed CK14 immunohistochemistry on 443 grade III invasive ductal carcinomas with extended clinical follow-up (mean 116 months), and we correlated CK14 immunopositivity (basal-like phenotype) with clinicopathological criteria.

Results

Eighty-eight of 443 (20%) tumours showed CK14 expression. CK14-positive tumours were more likely to be oestrogen receptor-negative (p < 0.0001) and axillary node-negative (p = 0.001) than were CK14-negative cases. CK14-positive cases developed less bone and liver metastases (hazard ratio [HR] 0.49, p = 0.01, and HR 0.53, p = 0.035, respectively) but more frequent brain metastases (HR 1.92, p = 0.051). In patients without metastatic disease, disease-free survival in CK14-positive cases was significantly better than in CK14-negative cases (HR 0.65, p = 0.005). In patients with metastatic disease, however, CK14 positivity was associated with a poorer prognosis (HR 1.84, p = 0.001). The overall survival in CK14-positive and -negative patients was similar at 5 years (60% and 59%, respectively), but the long-term survival was better in CK14-positive patients (HR 0.69, p = 0.02).

Conclusion

These results demonstrate that basal-like tumours differ in their biological behaviour from other tumours, with a distinct pattern of metastatic spread. Compared to other grade III tumours, basal-like tumours appear to have a relatively good long-term survival but survival after metastases is poor.
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Literature
1.
Ellis IO, Galea M, Broughton N, Locker A, Blamey RW, Elston CW: Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology. 1992, 20: 479-489.CrossRefPubMed
2.
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991, 19: 403-410.CrossRefPubMed
3.
Page DL, Jensen RA, Simpson JF: Routinely available indicators of prognosis in breast cancer. Breast Cancer Res Treat. 1998, 51: 195-208. 10.1023/A:1006122716137.CrossRefPubMed
4.
Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Edited by: Tavassoli FA, Devilee P. 2003, Lyon: IARC Press, 10-112. 336–357
5.
Page DL: Special types of invasive breast cancer, with clinical implications. Am J Surg Pathol. 2003, 27: 832-835. 10.1097/00000478-200306000-00016.CrossRefPubMed
6.
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: 9212-9217. 10.1073/pnas.96.16.9212.CrossRefPubMedPubMedCentral
7.
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: 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral
8.
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: 8418-8423. 10.1073/pnas.0932692100.CrossRefPubMedPubMedCentral
9.
Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, et al: Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005, 11: 5678-5685. 10.1158/1078-0432.CCR-04-2421.CrossRefPubMed
10.
Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET: Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA. 2003, 100: 10393-10398. 10.1073/pnas.1732912100.CrossRefPubMedPubMedCentral
11.
Murad TM, Scharpelli DG: The ultrastructure of medullary and scirrhous mammary duct carcinoma. Am J Pathol. 1967, 50: 335-360.PubMedPubMedCentral
12.
Santini D, Ceccarelli C, Taffurelli M, Pileri S, Marrano D: Differentiation pathways in primary invasive breast carcinoma as suggested by intermediate filament and biopathological marker expression. J Pathol. 1996, 179: 386-391. 10.1002/(SICI)1096-9896(199608)179:4<386::AID-PATH631>3.0.CO;2-V.CrossRefPubMed
13.
Gusterson BA, Warburton MJ, Mitchell D, Ellison M, Neville AM, Rudland PS: Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast diseases. Cancer Res. 1982, 42: 4763-4770.PubMed
14.
Heatley M, Maxwell P, Whiteside C, Toner P: Cytokeratin intermediate filament expression in benign and malignant breast disease. J Clin Pathol. 1995, 48: 26-32.CrossRefPubMedPubMedCentral
15.
Dairkee SH, Ljung BM, Smith H, Hackett A: Immunolocalization of a human basal epithelium specific keratin in benign and malignant breast disease. Breast Cancer Res Treat. 1987, 10: 11-20. 10.1007/BF01806130.CrossRefPubMed
16.
Malzahn K, Mitze M, Thoenes M, Moll R: Biological and prognostic significance of stratified epithelial cytokeratins in infiltrating ductal breast carcinomas. Virchows Arch. 1998, 433: 119-129. 10.1007/s004280050226.CrossRefPubMed
17.
van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, Torhorst J, Sauter G, Zuber M, Kochli OR, et al: Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol. 2002, 161: 1991-1996.CrossRefPubMedPubMedCentral
18.
Tsuda H, Morita D, Kimura M, Shinto E, Ohtsuka Y, Matsubara O, Inazawa J, Tamaki K, Mochizuki H, Tamai S, Hiraide H: Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid-tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation. Cancer Sci. 2005, 96: 48-53.CrossRefPubMed
19.
Tsuda H, Takarabe T, Hasegawa F, Fukutomi T, Hirohashi S: Large, central acellular zones indicating myoepithelial tumor differentiation in high-grade invasive ductal carcinomas as markers of predisposition to lung and brain metastases. Am J Surg Pathol. 2000, 24: 197-202. 10.1097/00000478-200002000-00005.CrossRefPubMed
20.
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: 1134-1139. 10.1016/S0046-8177(99)90028-X.CrossRefPubMed
21.
Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F, Schmitt FC: Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch. 2003, 443: 122-132. 10.1007/s00428-003-0859-2.CrossRefPubMed
22.
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: 5367-5374. 10.1158/1078-0432.CCR-04-0220.CrossRefPubMed
23.
Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, et al: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006, 295: 2492-2502. 10.1001/jama.295.21.2492.CrossRefPubMed
24.
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: 688-694. 10.1007/s00428-005-0010-7.CrossRefPubMed
25.
Laakso M, Loman N, Borg A, Isola J: Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors. Mod Pathol. 2005, 18: 1321-1328. 10.1038/modpathol.3800456.CrossRefPubMed
26.
Laakso M, Tanner M, Nilsson J, Wiklund T, Erikstein B, Kellokumpu-Lehtinen P, Malmstrom P, Wilking N, Bergh J, Isola J: Basoluminal carcinoma: a new biologically and prognostically distinct entity between basal and luminal breast cancer. Clin Cancer Res. 2006, 12: 4185-4191. 10.1158/1078-0432.CCR-06-0353.CrossRefPubMed
27.
Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S, Bishop T, Benitez J, Rivas C, Bignon YJ, et al: Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res. 2005, 11: 5175-5180. 10.1158/1078-0432.CCR-04-2424.CrossRefPubMed
28.
Jones C, Ford E, Gillett C, Ryder K, Merrett S, Reis-Filho JS, Fulford LG, Hanby A, Lakhani SR: Molecular cytogenetic identification of subgroups of grade III invasive ductal breast carcinomas with different clinical outcomes. Clin Cancer Res. 2004, 10: 5988-5997. 10.1158/1078-0432.CCR-03-0731.CrossRefPubMed
29.
Jones C, Nonni AV, Fulford L, Merrett S, Chaggar R, Eusebi V, Lakhani SR: CGH analysis of ductal carcinoma of the breast with basaloid/myoepithelial cell differentiation. Br J Cancer. 2001, 85: 422-427. 10.1054/bjoc.2001.1869.CrossRefPubMedPubMedCentral
30.
Jacquemier J, Padovani L, Rabayrol L, Lakhani SR, Penault-Llorca F, Denoux Y, Fiche M, Figueiro P, Maisongrosse V, Ledoussal V, et al: Typical medullary breast carcinomas have a basal/myoepithelial phenotype. J Pathol. 2005, 207: 260-268. 10.1002/path.1845.CrossRefPubMed
31.
Tot T: The cytokeratin profile of medullary carcinoma of the breast. Histopathology. 2000, 37: 175-181. 10.1046/j.1365-2559.2000.00889.x.CrossRefPubMed
32.
Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF, Macmillan D, Blamey RW, Ellis IO: 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 analyses. Int J Cancer. 2005, 116: 340-350. 10.1002/ijc.21004.CrossRefPubMed
33.
Abd El-Rehim DM, Pinder SE, Paish CE, Bell J, Blamey RW, Robertson JF, Nicholson RI, Ellis IO: Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol. 2004, 203: 661-671. 10.1002/path.1559.CrossRefPubMed
34.
Foulkes WD, Stefansson IM, Chappuis PO, Begin LR, Goffin JR, Wong N, Trudel M, Akslen LA: Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst. 2003, 95: 1482-1485.CrossRefPubMed
35.
Rakha EA, Putti TC, Abd El-Rehim DM, Paish C, Green AR, Powe DG, Lee AH, Robertson JF, Ellis IO: Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation. J Pathol. 2006, 208: 495-506. 10.1002/path.1916.CrossRefPubMed
36.
Fulford LG, Easton DF, Reis-Filho JS, Sofronis A, Gillett CE, Lakhani SR, Hanby A: Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast. Histopathology. 2006, 49: 22-34. 10.1111/j.1365-2559.2006.02453.x.CrossRefPubMed
37.
Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, Perou CM: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol. 2006, 19: 264-271. 10.1038/modpathol.3800528.CrossRefPubMed
38.
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: 10-21. 10.1111/j.1365-2559.2006.02467.x.CrossRefPubMed
39.
Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, Gong G: Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol. 2006, 37: 1217-1226. 10.1016/j.humpath.2006.04.015.CrossRefPubMed
40.
Lakhani SR, Jacquemier J, Sloane JP, Gusterson BA, Anderson TJ, van de Vijver MJ, Farid LM, Venter D, Antoniou A, Storfer-Isser A, et al: Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998, 90: 1138-1145. 10.1093/jnci/90.15.1138.CrossRefPubMed
41.
Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D, Savage K, Gillett CE, Schmitt FC, Ashworth A, et al: BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene. 2006 Oct 2
42.
Turner NC, Reis-Filho JS: Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 2006, 25: 5846-5853. 10.1038/sj.onc.1209876.CrossRefPubMed
43.
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: 1097-1104.CrossRefPubMed
44.
Gillett CE, Miles DW, Ryder K, Skilton D, Liebman RD, Springall RJ, Barnes DM, Hanby AM: Retention of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast. J Pathol. 2001, 193: 433-441. 10.1002/path.831.CrossRefPubMed
45.
King RJB, Redgrave S, Hayward JL, Millis RR, Rubens RD: The measurement of receptors for oestradiol and progesterone in human breast tumors. Steroid Receptor Assays in Human Breast Cancer. Edited by: King RJB. 1979, Cardiff: Omega Publishing, 55-72.
46.
Jensen EV, Green GL, Desombre ER: Immunochemical studies of estrogen receptors. Prog Clin Biol Res. 1987, 249: 283-305.PubMed
47.
Banerjee S, Reis-Filho JS, Ashley S, Steele D, Ashworth A, Lakhani SR, Smith IE: Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J Clin Pathol. 2006, 59: 729-735. 10.1136/jcp.2005.033043.CrossRefPubMedPubMedCentral
48.
Chappuis PO, Rosenblatt J, Foulkes WD: The influence of familial and hereditary factors on the prognosis of breast cancer. Ann Oncol. 1999, 10: 1163-1170. 10.1023/A:1008301314812.CrossRefPubMed
49.
Turner N, Tutt A, Ashworth A: Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer. 2004, 4: 814-819. 10.1038/nrc1457.CrossRefPubMed
Metadata
Title
Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival
Authors
Laura G Fulford
Jorge S Reis-Filho
Ken Ryder
Chris Jones
Cheryl E Gillett
Andrew Hanby
Douglas Easton
Sunil R Lakhani
Publication date
01-02-2007
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2007
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1636

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