Abstract
Introduction
Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic subtype of
breast cancer comprising approximately 0.5% to 5.0% of all invasive breast cancers
with a poor prognosis and limited therapeutic options.
Patients and Methods
We investigated MBC at our institution to evaluate outcomes and investigate the molecular
profile of our cohort to determine the presence of mutations for which there are targeted
therapies.
Results
We found our cohort to consist mainly of the matrix-producing variant (72%) with 48%
having the stereotypical estrogen receptor-negative/progesterone receptor-negative/human
epidermal growth factor receptor-2-negative phenotype. While the overall survival
of our cohort was an average of 1679 days (4.6 years), we had a surprising number
of patients with second primaries (40%) and distant metastases (40%), yet few recurrences
(12%). Molecular analysis of the tumors indicated that one gene mutation, CSFIR, was significantly associated with outcome (P = .021); however, the cohort was defined by frequent mutations in ERBB4 (36%), PIK3CA (48%), and FLT3 (60%), for which there are now targeted therapies.
Conclusion
While surgery is the appropriate first step in the management of this aggressive malignancy,
the collection of data pertaining to the use of targeted agents, although anecdotal,
may provide clues to better treatment for these patients.
Keywords
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References
- Metaplastic carcinoma of the breast: multimodality imaging and histopathologic assessment.Acta Radiologica. 2012; 53: 5-11
- Metaplastic breast carcinomas are enriched in markers of tumor initiating cells and epithelial to mesenchymal transition.Mod Pathol. 2012; 25: 178-184
- Classification of metaplastic carcinomas of the breast.Pathol Annu. 1992; 27: 89-119
- Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling analysis.Breast Cancer Res Treat. 2009; 117: 273-280
- Metaplastic breast cancer: clinical significance.Am J Surg. 2006; 191: 657-664
- Metaplastic breast cancer: clinical features and outcomes.Am Surg. 2005; 71: 725-730
- Metaplastic carcinoma of the breast: mammographic and sonographic findings.J Clin Ultrasound. 2000; 28: 179-186
- Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer.Breast Cancer Res Treat. 2010; 120: 627-637
- Metaplastic breast carcinoma: clinicopathologic features and prognostic value of triple negativity.Jpn J Clin Oncol. 2010; 40: 112-118
- Metaplastic carcinoma of the breast.Hum Pathol. 2010; 41: 960-970
- Unique characteristics and failure patterns of metaplastic breast cancer in contrast to invasive ductal carcinoma: a retrospective multicenter case-control study (KROG 13-07).Clin Breast Cancer. 2015; 15: e105-e115
- 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: 7859-7871
- Metaplastic breast cancer: clinical overview and molecular aberrations for potential targeted therapy.Curr Oncol Rep. 2015; 17: 431
Ion AmpliSeq Cancer Hotspot Panel v2. Available at: http://www.invitrogen.com. Accessed: August 1, 2015.
J. Craig Ventner Institute. SIFT. Available at: http://sift.jcvi.org/. Accessed: August 1, 2015.
Brigham and Women's Hospital. PolyPhen-2 prediction of functional effects of human nsSNPs. Available at: http://genetics.bwh.harvard.edu/pph2/index.shtml. Accessed: August 1, 2015.
- Metaplastic carcinoma of the breast clinical presentation, treatment results and prognostic factors.Acta Oncol. 2006; 45: 188-195
- Metaplastic breast cancer: a comparison between the most common histologies with poor immunohistochemistry factors.BMC Cancer. 2015; 15: 75-78
- Metaplastic breast carcinoma: A case report and systematic review of the literature.Pathol Int. 2011; 61: 582-588
Cubit. South Carolina demographics. Available at: http://www.southcarolina-demographics.com/greenville-county-demographics. Accessed: August 1, 2015.
- The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes.Clin Can Res. 2007; 13: 2329-2334
- Metaplastic breast cancer: prognosis and response to systemic therapy.Ann Oncol. 1999; 10: 413-419
- Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies.Exp Hematol Oncol. 2013; 2: 31-37
- A C-terminal mutant of CCAAT-enhancer-binding protein α (C/EBPα-Cm) downregulates Csf1r, a potent accelerator in the progression of acute myeloid leukemia with C/EBPα-Cm.Exp Hematol. 2015; 43: 300-308.e1
- Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy.Cancer Disc. 2011; 1: 54-67
- Proteolytic processing of ErbB4 in breast cancer.PLoS One. 2012; 7: e39413
- Characterization of a naturally occurring breast cancer subset enriched in epithelial-tomesenchymal transition and stem cell characteristics.Cancer Res. 2009; 69: 4116-4124
- A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations.Br J Haematol. 2015; 169: 694-700
- Genomic profiling of advanced-stage, metaplastic breast carcinoma by next-generation sequencing reveals frequent, targetable genomic abnormalities and potential new treatment options.Arch Pathol Lab Med. 2015; 139: 642-649
- Analysis of the genome to personalize therapy for melanoma.Oncogene. 2010; 29: 5545-5555
- A phase I study of daily afatinib, an irreversible ErbB family blocker, in combination with weekly paclitaxel in patients with advanced solid tumours.Eur J Can. 2015; 51: 2275-2284
- Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study.Ann Oncol. 2015; 26: 325-332
- Prospective biomarker analysis of the randomized CHER-LOB study evaluating the dual anti-HER2 treatment with trastuzumab and lapatinib plus chemotherapy as neoadjuvant therapy for HER2-positive breast cancer.Oncologist. 2015; 20: 1001-1010
A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors. Available at: www.clinicaltrials.gov. Accessed: August 15, 2016.
- Gene mutations and molecularly targeted therapies in acute myeloid leukemia.Am J Blood Res. 2013; 3: 29-51
- Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.N Engl J Med. 2014; 371: 1005-1015
Article Info
Publication History
Published online: July 22, 2016
Accepted:
July 18,
2016
Received in revised form:
June 26,
2016
Received:
October 9,
2015
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
