Higher efficacy and complete response with administration of eribulin for recurrent squamous cell breast carcinoma: A case report
- Authors:
- Published online on: July 19, 2018 https://doi.org/10.3892/mco.2018.1676
- Pages: 318-320
Abstract
Introduction
Squamous cell carcinoma is a type of metaplastic carcinoma; metaplastic carcinoma is characterized as carcinoma of the breast ductal tissue and stratified squamous epithelial tissue followed by their consequent differentiation into bone, cartilage and osteocartilaginous tissue. It has been reported that metaplastic breast carcinoma accounts for <1% of all breast carcinomas, and it is characterized by large size, low incidence of lymphatic metastasis and high incidence of triple-negative phenotype (1–3). While chemotherapy for metaplastic carcinoma is commonly similar to that of invasive ductal carcinoma, a number of studies in the literature report a poor response to conventional chemotherapy (1,4,5). We herein report our experience with eribulin administration in a case of recurrent squamous cell carcinoma of the breast and discuss the relevant literature.
Case report
A 42-year-old woman with carcinoma of the right breast (T4N3aM0, stage IIIC) underwent mastectomy and level III axillary lymph node dissection (Fig. 1).
Pathological examination revealed squamous cell carcinoma negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (Fig. 2). Six cycles of postoperative adjuvant chemotherapy with cyclophosphamide 500 mg/m2, epirubicin 75 mg/m2 and fluorouracil 500 mg/m2 (CEF regimen) were administered, following which an increase in the size of the ipsilateral sternal lymph nodes was observed. No other metastatic lesions were found on computed tomography (CT) scans, and the patient was subjected to lymphadenectomy with pleural drainage. Pathological examination of the resected nodes demonstrated metastatic squamous cell carcinoma. Docetaxel (75 mg/m2) was administered as adjuvant therapy; however, allergic symptoms developed, including respiratory distress and palpitations, and docetaxel was discontinued. Radiotherapy to the right thoracic wall and the right supraclavicular lymph node (60 Gy) was next administered. However, enlargement of the ipsilateral supraclavicular lymph node was observed 3 months after radiotherapy. Lymphadenopathy (lymph node enlarged to 2 cm in diameter) was identified on ultrasound examination, and fine-needle aspiration cytology confirmed the presence of metastatic squamous cell carcinoma. Fluorodeoxyglucose positron emission tomography (FDG-PET)-CT revealed accumulation in the anterior thoracic wall close to the previous surgical site (Fig. 3). Consequently, eribulin (1.4 mg/m2) was administered as initial therapy. The lymph node was not palpable at 1 month after therapy initiation, and at 3 months after chemotherapy the enlargement had completely disappeared, as demonstrated on a CT examination. No metastatic lymph node or thoracic wall FDG accumulation was observed on PET-CT 11 months after treatment initiation (Fig. 4). After 17 months of treatment, the patient remained metastasis-free. During those 17 months, no major side effects were observed although peripheral neuropathy not affecting daily life grade 1 peripheral neurotoxicity occurred.
Discussion
It is generally recommended that the protocols for the treatment of invasive ductal carcinoma of breast cancer are applied for the treatment of squamous cell carcinoma. However, poor efficacy of chemotherapy in recurrent carcinomas, including squamous cell carcinoma, has been reported to date. While previous studies have reported the use of anthracyclines and taxanes, to the best of our knowledge, there are yet no published reports on the efficacy of eribulin. We herein discuss the possible reasons for the observed effectiveness of eribulin in the treatment of metaplastic breast carcinoma.
In addition to its effectiveness against the epithelial component, it is possible that eribulin is also effective against the mesenchymal component of the carcinoma. Drug regimens including adriamycin, which is also indicated for soft tissue tumors with a mesenchymal component, have been reported to significantly prolong progression-free survival in metaplastic carcinomas compared with other regimens. Reduced incidence of hepatic metastasis has also been reported with the use of ifosfamide and etoposide, which are used for treating soft tissue tumors (6). In Study 309, eribulin was found to be effective against liposarcoma or leiomyosarcoma (7). Eribulin promotes DNA repair, the inhibition of which is characteristic of metaplastic carcinomas, and is thus considered a more effective therapeutic agent compared with adriamycin, of which the primary mechanism of action involves the inhibition of DNA synthesis.
Furthermore, in metaplastic carcinomas, tumors including squamous epithelial and sarcomatous components exhibit increased expression of TWIST and SNAIL 2 transcription factors, suggesting an association with epithelial-to-mesenchymal transition (EMT) (8,9). Reports indicate that the occurrence of EMT in cancer cells coincides with the development of resistance to various anticancer agents. Several anticancer agents have been reported to induce EMT and are considered to be involved in drug resistance. Albeit in an in vitro study, eribulin has been shown to inhibit Smad 2 and Smad 3 phosphorylation via transforming growth factor-β induction or MET inhibition. These characteristic mechanisms of action of eribulin are considered to contribute to the effectiveness of the therapy in the present case.
Acknowledgements
The authors would like to thank Shiro Sugihara for the pathological examinations and interpretations.
Funding
No funding was received.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
Authors' contributions
YG designed the study and wrote the initial draft of the manuscript. TY contributed to the analysis and interpretation of data and assisted in the preparation of the manuscript. MK critically reviewed the manuscript. All authors have read and approved the final version of the manuscript.
Ethics approval and consent to participate
The study was conducted in accordance with the principles of the Declaration of Helsinki.
Patient consent for publication
This patient and her family were informed that the data from her case would be submitted for publication and provided written informed consent.
Competing interests
The authors declare that they have no competing interests.
Glossary
Abbreviations
Abbreviations:
CEF |
cyclophosphamide-epirubicin-fluorouracil |
FDG-PET/CT |
fluorodeoxyglucose positron emission tomography-computed tomography |
EMT |
epithelial-to-mesenchymal transition |
TGF-β |
transforming growth factor-β |
References
Rayson D, Adjei AA, Suman VJ, Wold LE and Ingle JN: Metaplastic breast cancer: prognosis and response to systemic therapy. Ann Oncol. 10:413–419. 1999. View Article : Google Scholar : PubMed/NCBI | |
Pezzi CM, Patel-Parekh L, Cole K, Franko J, Klimberg VS and Bland K: Characteristics and treatment of metaplastic breast cancer: analysis of 892 cases from the National Cancer Data Base. Ann Surg Oncol. 14:166–173. 2007. View Article : Google Scholar : PubMed/NCBI | |
Lee H, Jung SY, Ro JY, Kwon Y, Sohn JH, Park IH, Lee KS, Lee S, Kim SW, et al: Metaplastic breast cancer: clinicopathological features and its prognosis. J Clin Pathol. 65:441–446. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chen IC, Lin CH, Huang CS, Lien HC, Hsu C, Kuo WH, Lu YS, Cheng AL, et al: Lack of efficacy to systemic chemotherapy for treatment of metaplastic carcinoma of the breast in the modern era. Breast Cancer Res Treat. 130:345–351. 2011. View Article : Google Scholar : PubMed/NCBI | |
Abouharb S and Moulder S: Metaplastic breast cancer: clinical overview and molecular aberrations for potential targeted therapy. Curr Oncol Rep. 17:4312015. View Article : Google Scholar : PubMed/NCBI | |
Brown-Glaberman U, Graham A and Stopeck A: A case of metaplastic carcinoma of the breast responsive to chemotherapy with Ifosfamide and Etoposide: improved antitumor response by targeting sarcomatous features. Breast J J. 16:663–665. 2010. View Article : Google Scholar | |
Schoffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, et al: Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 387:1629–1637. 2016. View Article : Google Scholar : PubMed/NCBI | |
Karreth F and Tuveson DA: Twist induces an epithelial-mesenchymal transition to facilitate tumor metastasis. Cancer Biol Ther. 3:1058–1059. 2004. View Article : Google Scholar : PubMed/NCBI | |
Valsesia-Wittmann S, Magdeleine M, Dupasquier S, Garin E, Jallas AC, Combaret V, Krause A, Leissner P and Puisieux A: Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Cancer Cell. 6:625–630. 2004. View Article : Google Scholar : PubMed/NCBI |