Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Experimental Hematology & Oncology
Published in: Experimental Hematology & Oncology 1/2013

Open Access 01-12-2013 | Review

Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies

Authors: Theresa L Schwartz, Harveshp Mogal, Christos Papageorgiou, Jula Veerapong, Eddy C Hsueh

Published in: Experimental Hematology & Oncology | Issue 1/2013

Login to get access

Abstract

Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer that tends to have an aggressive clinical presentation as well as a variety of distinct histologic designations. Few systemic treatment options are available for MBC, as it has consistently shown a suboptimal response to standard chemotherapy regimens. These characteristics result in a worse overall prognosis for patients with MBC compared to those with standard invasive breast cancer. Due to its rarity, data focusing on MBC is limited. This review will discuss the clinical presentation, breast imaging findings, histologic and molecular characteristics of MBC as well as potential future research directions.
Literature
1.
Luini A, Aguilar M, Gatti G, et al.: Metaplastic carcinoma of the breast, an unusual disease with worse prognosis: the experience of the European Institute of Oncology and review of the literature. Breast Cancer Res Treat 2007, 101: 349–353. 10.1007/s10549-006-9301-1PubMedCrossRef
2.
Tavassoli FA: Classification of metaplastic carcinomas of the breast. Pathol Annu 1992,27(Pt 2):89–119.PubMed
3.
Fritz A, Percy C, Jack A, Solin LH: In International Classification of Diseases of Oncology 3. Geneva: World Health Organization; 2000.
4.
Rayson D, Adjei AA, Suman VJ, Wold LE, Ingle JN: Metaplastic breast cancer: Prognosis and response to systemic therapy. Ann Oncol 1999,10(4):413–419. 10.1023/A:1008329910362PubMedCrossRef
5.
Weigelt B, Kreike B, Reis-Filho JA: Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling analysis. Breast Cancer Res Treat 2009, 117: 273–280. 10.1007/s10549-008-0197-9PubMedCrossRef
6.
Tse GM, Tan PH, Putti TC, et al.: Metaplastic carcinoma of the breast: a clinicopathological review. J Clin Pathol 2006, 59: 1079–1083. 10.1136/jcp.2005.030536PubMedCentralPubMedCrossRef
7.
Al Sayed AD, El Weshi AN, Tulbah AM, et al.: Metaplastic carcinoma of the breast clinical presentation, treatment results and prognostic factors. Acta Oncol 2006, 45: 188–195. 10.1080/02841860500513235PubMedCrossRef
8.
Jung SY, Kim HY, Nam BH, et al.: Worse prognosis of metaplastic breast cancer patients than other patients with triple negative breast cancer. Breast Cancer Res Treat 2000, 120: 627–637.CrossRef
9.
Okada N, Hasebe T, Iwasaki M, et al.: Metaplastic carcinoma of the breast. Hum Pathol 2010, 41: 960–970. 10.1016/j.humpath.2009.11.013PubMedCrossRef
10.
Bae SY, Lee SK, Koo MY, et al.: The prognoses of metaplastic breast cancer patients compared to those of triple negative breast cancer patients. Breast Cancer Res Treat 2011, 126: 471–478. 10.1007/s10549-011-1359-8PubMedCrossRef
11.
Kaufman MW, Marti JR, Gallager HS, Hoehn JL: Carcinoma of the breast with pseudosarcomatous metaplasia. Cancer 1984, 53: 1908–1917. 10.1002/1097-0142(19840501)53:9<1908::AID-CNCR2820530917>3.0.CO;2-FPubMedCrossRef
12.
Beatty JD, Atwood M, Tickman R, Reiner M: Metaplastic breast cancer: clinical significance. Am J Surg 2006, 191: 657–664. 10.1016/j.amjsurg.2006.01.038PubMedCrossRef
13.
Chao TC, Wang CS, Chen SC, Chen MF: Metaplastic carcinomas of the breast. J Surg Oncol 1999, 71: 220–225. 10.1002/(SICI)1096-9098(199908)71:4<220::AID-JSO3>3.0.CO;2-LPubMedCrossRef
14.
Wargotz ES, Norris HJ: Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma. Hum Pathol 1989, 20: 628–635. 10.1016/0046-8177(89)90149-4PubMedCrossRef
15.
Wargotz ES, Deos PH, Norris HJ: Metaplastic carcinomas of the breast. II. Spindle cell carcinoma. Hum Pathol 1989, 20: 732–740. 10.1016/0046-8177(89)90065-8PubMedCrossRef
16.
Gutman H, Pollock RE, Janjan NA, et al.: Biologic distinctions and therapeutic implications of sarcomatoid metaplasia of epithelial carcinoma of the breast. J Am Coll Surg 1995, 180: 193–199.PubMed
17.
Wargotz ES, Norris HJ: Metaplastic carcinomas of the breast. III. Carcinosarcoma. Cancer 1989, 64: 1490–1499. 10.1002/1097-0142(19891001)64:7<1490::AID-CNCR2820640722>3.0.CO;2-LPubMedCrossRef
18.
Carter CL, Allen C, Henson DE: Relation of tumor size, lymph node status and survival in 24,740 breast cancer cases. Cancer 1969, 63: 181–187.CrossRef
19.
Yang WT, Hennessy B, Broglio K, Mills C, Sneige N, Davis WG, Valero V, Hunt KK, Gilcrease MZ: Imaging differences in metaplastic and invasive ductal carcinomas of the breast. Am J Roentgenol 2007, 189: 1288–1292. 10.2214/AJR.07.2056CrossRef
20.
Shin HJ, Kim HH, Kim SM, Kim DB, Kim MJ, Gong G, et al.: Imaging of metaplastic carcinoma with chondroid differentiation of the breast. Am J Roentgenol 2007, 188: 691–696. 10.2214/AJR.05.0831CrossRef
21.
Park JM, Han BK, Moon WK, Choe YH, Ahn SH, Gong G: Metaplastic carcinoma of the breast: Mammographic and sonographic findings. J Clin Ultrasound 2000, 28: 179–186. 10.1002/(SICI)1097-0096(200005)28:4<179::AID-JCU5>3.0.CO;2-YPubMedCrossRef
22.
Brenner J, Turner RR, Schiller V, Arndt RD, Giuliano A: Metaplastic carcinoma of the breast: report of three cases. Cancer 1998,82(6):1082–1087. 10.1002/(SICI)1097-0142(19980315)82:6<1082::AID-CNCR11>3.0.CO;2-2PubMedCrossRef
23.
Gunhan-Bilgen I, Memis A, Ustun EE, Zekioglu O, Ozdemir N: Metaplastic carcinoma of the breast: clinical, mammographic and sonographic findings with histopathologic correlation. Am J Roentgenol 2002, 178: 1421–1425. 10.2214/ajr.178.6.1781421CrossRef
24.
Velasco M, Santamaría G, Ganau S, Farrús B, Zanón G, Romagosa C, et al.: MRI of metaplastic carcinoma of the breast. Am J Roentgenol 2005, 184: 1274–1278. 10.2214/ajr.184.4.01841274CrossRef
25.
Park HS, Park S, Kim JH, Lee JH, Choi SY, Park BW, Lee KS: Clinicopathologic features and outcomes of metaplastic breast carcinoma: comparison with invasive ductal carcinoma of the breast. Yonsei Med J 2010,51(6):864–869. 10.3349/ymj.2010.51.6.864PubMedCentralPubMedCrossRef
26.
Pezzi CM, Patel-Parekh L, Cole K, Franko J, Klimberg S, Bland K: Characteristics and treatment of metaplastic breast cancer: analysis of 892 cases from the National Cancer Database. Ann Surg Onc 2006,14(1):166–173. 10.1245/s10434-006-9124-7CrossRef
27.
Chen IC, Lin CH, Huang CS, Lien HC, Hsu C, Kuo WH, Lu YS, Cheng AL: Lack of efficacy to systemic chemotherapy for treatment of metaplastic carcinoma of the breast in the modern era. Breast Cancer Res Treat 2011, 130: 345–351. 10.1007/s10549-011-1686-9PubMedCrossRef
28.
Hennessy BT, Giordano S, Broglio K, Duan Z, Trent J, Buchholz TA, Babiera G, Hortobagyi GN, Valero V: Biphasic metaplastic sarcomatoid carcinoma of the breast. Ann Oncol 2006, 17: 605–613. 10.1093/annonc/mdl006PubMedCrossRef
29.
Cardoso F, Bedard PL, Winer EP, Pagani O, Senkus-Konefka E, Fallowfield LJ, Kyriakides S, Costa A, Cufer T, Albain KS: International guidelines for management of metastatic breast cancer: combination vs sequential single-agent chemotherapy. J Natl Cancer Inst 2009, 101: 1174–1181. 10.1093/jnci/djp235PubMedCentralPubMedCrossRef
30.
Huvos AG, Lucas JC Jr, Foote FW Jr: Metaplastic breast carcinoma: rare form of mammary cancer. N Y State J Med 1973, 73: 1078–1082.PubMed
31.
Tavassoli FA, Devilee P: World Health Organization classification of tumors: tumors of the breast and female genital organs. Pathology and genetics of tumors of the digestive system. In World Health Organization Classification of Tumors. Lyon, France: IARC Press; 2003:37–41.
32.
Ayar S, Dysee L, Carter E: Matrix-producing carcinoma: a rare variant of metaplastic breast carcinoma with heterologous elements. Breast J 2010, 16: 420–423.PubMed
33.
Wargotz ES, Norris HJ: Metaplastic carcinomas of the breast. V: Metaplastic carcinoma with osteoclastic giant cells. Hum Pathol 1990, 21: 1142–1150. 10.1016/0046-8177(90)90151-TPubMedCrossRef
34.
Wargotz ES, Norris HJ: Metaplastic carcinomas of the breast. IV: Squamous cell carcinoma of ductal origin. Cancer 1990, 65: 272–276. 10.1002/1097-0142(19900115)65:2<272::AID-CNCR2820650215>3.0.CO;2-6PubMedCrossRef
35.
Oberman HA: Metaplastic carcinoma of the breast. Am J Surg Pathol 1987, 11: 918–929. 10.1097/00000478-198712000-00002PubMedCrossRef
36.
Zhuang Z, Lininger RA, Man YG, Albuquerque A, Merino MJ, Tavassoli FA: Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity. Mod Pathol 1997, 10: 354–362.PubMed
37.
George E, Manivel JC, Dehner LP, Wick MR: Malignant mixed Mullerian tumors: an immunohistochemical study of 47 cases, with histogenetic considerations and clinical correlation. Hum Pathol 1991, 22: 215–223. 10.1016/0046-8177(91)90153-GPubMedCrossRef
38.
Chhieng C, Cranor M, Lesser ME, Rosen PP: Metaplastic carcinoma of the breast with osteocartilaginous heterologous elements. Am J Surg Pathol 1998, 22: 188–194. 10.1097/00000478-199802000-00006PubMedCrossRef
39.
Wada H, Enomoto T, Tsujimoto M, Nomura T, Murata Y, Shroyer KR: Carcinosarcoma of the breast: molecular-biological study for analysis of histogenesis. Hum Pathol 1998, 29: 1324–1328. 10.1016/S0046-8177(98)90266-0PubMedCrossRef
40.
Wang X, Mori I, Tang W, et al.: Metaplastic carcinoma of thebreast: p53 analysis identified the same point mutation in the three histologic components. Mod Pathol 2001, 14: 1183–1186. 10.1038/modpathol.3880456PubMedCrossRef
41.
42.
Soussi T: The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann N Y Acad Sci 2000, 910: 121–137. discussion 137–139PubMedCrossRef
43.
Berns EM, van Staveren IL, Look MP, Smid M, Klijn JG, Foekens JA: Mutations in residues of TP53 that directly contact DNA predict poor outcome in human primary breast cancer. Br J Cancer 1998, 77: 1130–1136. 10.1038/bjc.1998.187PubMedCentralPubMedCrossRef
44.
DeCremoux P, Salomon AV, Liva S, et al.: p53 mutation as a genetic trait of typical medullary breast carcinoma. J Natl Cancer Inst 1999, 91: 641–643. 10.1093/jnci/91.7.641CrossRef
45.
Marchetti A, Buttitta F, Pellegrini S, et al.: p53 mutations and histological type of invasive breast carcinoma. Cancer Res 1993, 53: 4665–4669.PubMed
46.
Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavanee W, Vogelstein B: Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature 1992, 355: 846–847. 10.1038/355846a0PubMedCrossRef
47.
Lien HC, Lin CW, Mao TL, Kuo SH, Hsiao CH, Huang CS: p53 overexpression and mutation in metaplastic carcinoma of the breast: genetic evidence for a monoclonal origin of both the carcinomatous and the heterogeneous sarcomatous components. J Pathol 2004,204(2):131–139. 10.1002/path.1624PubMedCrossRef
48.
49.
Wada H, Enomoto T, Fujita M, Yoshino K, Nakashima R, Kurachi H, Haba T, Wakasa K, Shroyer KR, Tsujimoto M, Hongyo T, Nomura T, Murata Y: Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res 1997,57(23):5379–5385.PubMed
50.
Emoto M, Iwasaki H, Ishiguro M, Kikuchi M, Horiuchi S, Saito T, Tsukamoto N, Kawarabayashi T: Angiogenesis in carcinosarcomas of the uterus: differences in the microvesel density and expression of vascular endothelial growth factor between the epithelial and mesenchymal elements. Hum Pathol 1999,30(10):1232–1241. 10.1016/S0046-8177(99)90043-6PubMedCrossRef
51.
Tanimoto H, Shigemasa K, Sasaki M, Katayama H, Kusumi I, Parmley TH, O’Brien TJ, Ohama K: Differential expression of matrix metalloprotease-7 in each component of uterine carcinosarcoma. Oncol Rep 2000,7(6):1209–1212.PubMed
52.
Lien HC, Hsiao YH, Lin YS, et al.: Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial-mesenchymal transition. Oncogene 2007, 26: 859–871. 10.1038/sj.onc.1209840CrossRef
53.
Castilla MA, Diaz-Martin J, Sarrio D, Romero-Perez L, Lopez-Garcia A, Vieites B, Biscuola M, Ramiro-Fuentes S, Isacke C, Palacios J: MicroRNA-200 family modulation in distinct breast cancer phenotypes. PLoS One 2012,7(10):1–9.CrossRef
54.
Hayes MJ, Thomas D, Emmons A, Giordano T, Kleer C: Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin Cancer Res 2008,14(13):4038–4044. 10.1158/1078-0432.CCR-07-4379PubMedCentralPubMedCrossRef
55.
Hennessy BT, Gonzalez-Angulo A-M, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee J-S, Fridlyand J, Sahin A, Agarwal R, Joy C, Liu W, Stivers D, Baggerly K, Carey M, Lluch A, Monteagudo C, He X, Weigman V, Fan C, Palazzo J, Hortobagyi GN, Nolden LK, Wang NJ, Valero V, Gray JW, Perou CM, Mills GB: Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res 2009, 69: 4116–4124.PubMedCentralPubMedCrossRef
56.
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.xPubMedCrossRef
57.
Leibl S, Gogg-Kammerer M, Sommersacher A, Denk H, Moinfar F: Metaplastic breast carcinomas: are they of myoepithelialdifferentiation? Immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers. Am J Surg Pathol 2005, 29: 347–353. 10.1097/01.pas.0000152133.60278.d2PubMedCrossRef
58.
Dunne B, Lee AH, Pinder SE, Bell JA, Ellis IO: An immunohistochemical study of metaplastic spindle cell carcinoma, phyllodes tumor and fibromatosis of the breast. Hum Pathol 2003, 34: 1009–1015. 10.1053/S0046-8177(03)00414-3PubMedCrossRef
59.
Popnikolov NK, Ayala AG, Graves K, Gatalica Z: Benign myoepithelial tumors of the breast have immunophenotypic characteristics similar to metaplastic matrix-producing and spindle cell carcinomas. Am J Clin Patho 2003, 120: 161–167. 10.1309/G6CTR8MDTFUW19XVCrossRef
60.
Reis-Filho JS, Steele D, Di Palma S, Jones RL, Savage K, James M, et al.: Distribution and significance of nerve growthfactor receptor (NGFR/p75 (NTR)) in normal, benign andmalignant breast tissue. Mod Pathol 2006, 19: 307–319. 10.1038/modpathol.3800542PubMedCrossRef
61.
Reis-Filho JS, Milanezi F, Paredes J, Silva P, Pereira EM, Maeda SA, et al.: Novel and classic myoepithelial/stem cell markers inmetaplastic carcinomas of the breast. Appl Immunohistochem M M 2003, 11: 1–8.
62.
Carter MR, Hornick JL, Lester S, Fletcher CDM: Spindle cell(sarcomatoid) carcinoma of the breast: a clinicopathologic andimmunohistochemical analysis of 29 cases. Am J Surg Pathol 2006, 30: 300–309.PubMed
63.
Livasy CA, Karaca G, Nanda R, Tretiakova MS, Olopade OI, Moore DT, et al.: Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006, 19: 264–271. 10.1038/modpathol.3800528PubMedCrossRef
64.
Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al.: Immunohistochemical and clinical characterization of the basallike subtype of invasive breast carcinoma. Clin Cancer Res 2004, 10: 5367–5374. 10.1158/1078-0432.CCR-04-0220PubMedCrossRef
65.
Reis-Filho JS, Milanezi F, Carvalho S, Simpson PT, Steele D, Savage K, et al.: Metaplastic breast carcinomas show EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridization analysis. Breast Cancer Res 2005, 7: 1028–1035. 10.1186/bcr1341CrossRef
66.
Leibl S, Moinfar F: Metaplastic breast carcinomas are negative forHer-2 but frequently express EGFR (Her-1): potential relevance toadjuvant treatment with EGFR tyrosine kinase inhibitors? J Clin Pathol 2005, 58: 700–704. 10.1136/jcp.2004.025163PubMedCentralPubMedCrossRef
67.
Bossuyt V, Fadare O, Martel M, Ocal IT, Burtness B, Moinfar F, et al.: Remarkably high frequency of EGFR expression in breast carcinomas with squamous differentiation. Int J Surg Pathol 2005, 13: 319–327. 10.1177/106689690501300403PubMedCrossRef
68.
Reis-Filho JS, Pinheiro C, Lambros MB, et al.: EGFR amplification and lack of activating mutations in metaplastic breast carcinomas. J Pathol 2006, 209: 445–453. 10.1002/path.2004PubMedCrossRef
69.
Sebolt-Leopold JS: Development of anticancer drugs targeting the MAP kinase pathway. Oncogene 2000, 19: 6594–6599. 10.1038/sj.onc.1204083PubMedCrossRef
70.
Calabrese C, Poppleton H, Kocak M, et al.: A perivascular niche for brain tumor stem cells. Cancer Cell 2007, 11: 69–82. 10.1016/j.ccr.2006.11.020PubMedCrossRef
71.
Bellino R, Arisio R, D’Addato F, et al.: Metaplastic breast carcinoma: Pathology and clinical outcome. Anticancer Res 2003, 23: 669–673.PubMed
72.
Kochhar R, Howard EM, Umbreit JN, et al.: Metaplastic breast carcinoma with squamous differentiation: Molecular and clinical analysis of six cases. Breast J 2005, 11: 367–369. 10.1111/j.1075-122X.2005.00031.xPubMedCrossRef
73.
Pantuck AJ, Zeng G, Belldegrun AS, et al.: Pathobiology, prognosis, and targeted therapy for renal cell carcinoma: exploiting the hypoxia-induced pathway. Clin Cancer Res 2003, 9: 4641–4652.PubMed
74.
Del Bufalo D, Ciuffreda L, Trisciuoglio D, et al.: Antiangiogenic potential of the Mammalian target of rapamycin inhibitor temsirolimus. Cancer 2006, 66: 5549–5554.
75.
Huynh H, Chow PK, Palanisamy N, et al.: Bevacizumab and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma. J Hepatol 2008, 49: 52–60. 10.1016/j.jhep.2008.02.022PubMedCrossRef
76.
Moulder S, Moroney J, Helgason T, Wheler J, Booser D, Albarracin C: Responses to liposomal doxorubicin, bevacizumab, and temsirolimus in metaplastic carcinoma of the breast: biologic rationale and implications for stem-cell research in breast cancer. J Clin Oncol 2011, 29: e572–575. 10.1200/JCO.2010.34.0604PubMedCrossRef
Metadata
Title
Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies
Authors
Theresa L Schwartz
Harveshp Mogal
Christos Papageorgiou
Jula Veerapong
Eddy C Hsueh
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2013
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/2162-3619-2-31

Other articles of this Issue 1/2013

Experimental Hematology & Oncology 1/2013 Go to the issue

Research

In vitro and in vivo properties of CD133 expressing cells from human lung cancer cell lines

Research

Clinical and laboratory characteristics of adolescents with platelet function disorders and heavy menstrual bleeding

Research

A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC

Review

The forgotten tale of immunoglobulin allotypes in cancer risk and treatment

Research

Targeting early B-cell receptor signaling induces apoptosis in leukemic mantle cell lymphoma

Research

Clinicopathological analysis of primary adrenal diffuse large B-cell lymphoma: effectiveness of rituximab-containing chemotherapy including central nervous system prophylaxis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits