Discussion
Metaplastic breast cancer is an infrequent cancer of the breast, the identification, elucidation and management of which is an evolving field, gaining momentum over the last two decades [8].
The median age of presentation is 48-59 years i.e. perimenopausal women. [9]  Earlier database analyses have shown a higher mean age of diagnosis of 61 years. [10] Our patient did not fit this demographic, with a younger age of presentation and pre-menopausal status. A higher prevalence is noted in African-American and Hispanic women. [10]   There is a need to extend the databases to include Asian and African populations to identify risk groups in low-middle-income countries.
Clinically, the majority present with a large, well-circumscribed mass, usually >5cm. [11] MpBC tends to have a large tumour size, rapid growth and less axillary lymph node involvement. [6,12]  The present case had a similar large size at presentation keeping with the literature.
The diagnosis of MpBC is histopathological, thus is highly dependent on postoperative pathology. There is no typical imaging to discern it from the other variants of BC, and pathologically, as it is a mixture of two or more homologous or heterologous components, it can be very difficult to differentiate it from other rare benign or malignant histologies. [13]
Metaplastic carcinomas are on the spectrum of basal carcinomas, displaying a basal/myoepithelial and epithelial-to-mesenchymal molecular structure. [14]   It is a rare heterogenous subtype characterised by squamous, spindle cell and mesenchymal phenotype with or without conventional adenocarcinoma component. [15]
Histopathological categorization is of cardinal importance as it guides the prognosis with the squamous variant being the worst. Diagnosis from cytology is challenging as both epithelial and mesenchymal elements are essential components. They are known to display positivity for cytokeratin, S-100 and vimentin or myoepithelial markers like CD10, p63, and smooth muscle actin. These tumours are mostly sporadic but can arise from previous lesions like fibroadenoma, spindle cell carcinoma, papilloma and complex sclerosing lesions. [16] Beatty et al. identified 24 MpBC cases which showed high nuclear grade, negative ER/PR and HER2 status, EGFR positivity and no significant difference in multidisciplinary treatment patterns, recurrence, or survival, in comparison to typical BC. [17] Prior studies have found that MpBC typically has molecular alterations in epithelial-to-mesenchymal transition; amplification of epidermal growth factor receptor (EGFR/HER1); PI3K/AKT, nitric oxide and Wnt/β-catenin signalling; altered immune response; and cell cycle dysregulation. [6]
First described in 1987, low-grade adenosquamous carcinoma of the breast is a rare variant of metaplastic carcinoma. This variant is characterised by having both squamous and glandular differentiation embedded in a bland background of spindle cells. [18, 19] We describe a similar histological description in our case, and the patient being cancer-free 3 years on, provides further evidence of the favourable prognosis due to the low-grade nature of these tumours.
Most MpBC is triple-negative tumours, and thus the management principles follow those of conventional TNBC. These cancers are treated with anthracycline, taxane and platinum-based chemotherapy. The larger size of the tumours, lack of hormone therapy as a systemic treatment, and the increased risk of metastasis make a case for the increased use of systemic chemotherapy though the literature bases lack substantial evidence to support this practice. [5, 10] Our patient received NACT, following which the axillary nodes did shrink (negative axillary dissection specimen), but the tumour however grew in size. The cut section did however demonstrate a large area of necrosis, which was pre-empted by the interval sonomammogrphy showing internal echoes. Variation in response to NACT exists based on the histologic subtype, with some benefit observed in matrix-producing MpBC. [9] The role of NACT in MpBC is still unclear, but may continue to remain the standard of practice due to the higher risk of metastasis in the absence of it, and until newer novel therapies are developed.
There have been limited studies regarding the use of adjuvant radiotherapy, most of which have demonstrated better overall survival (OS), DFS and reduced recurrence rate. [20]  Following the conventional principles of BC treatment, radiation to the tumour bed is commonly given with BCS, which has shown some favourable outcomes. Unfortunately, the published literature has small patient cohorts. [21]
Most patients with MpBc receive surgery as a viable treatment option, especially if presented early with locally advanced operable tumours. Both mastectomy and breast conservation surgery were performed, with the former being more commonly performed due to larger tumour size, and high tumour:normal breast tissue ratio. [10, 22]
Novel molecular targeted therapies such as poly ADP-ribose polymerase (PARP) inhibitors, angiogenesis inhibitors (bevacizumab), protein kinase inhibitors and mammalian target of Rapamycin (mTOR) inhibitors (temsirolimus or everolimus) have shown good potential for research in MpBC. The increased expression of EGFR provides an opportunity for targeted tumour therapy in these tumours. [13]
Predictors of a poorer outcome are the presence of skin invasion, younger age at presentation (<39 years), and appearance of squamous cell carcinoma in the lymph nodes. [11, 16]
MpBC represents a heterogeneity in breast malignancies, with a need for tailoring treatment for the different variants of breast cancer, rather than approaching it as a single entity. The scarcity of reported cases of this tumour makes it a therapeutic challenge for oncologists worldwide. The lack of clear guidelines for management warrants the need for more research on the entity, with a special focus on targeted therapy. It also emphasises the need to identify variants of BC and focus on a tailored approach, rather than a one-size-fits-all approach.