Survival in metaplastic breast carcinoma: A case series

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare type of breast cancer (0.20–1.00% of all cases). With a more aggressive clinical course, MBC frequently presents as a triple-negative subtype. OBJECTIVE: To describe a case series, analyzing patients survival in four MBC cases. METHODS: The cases were obtained from 532 medical records of breast cancer patients (0.7% of the total). RESULTS: All patients were female. Mean patient age was 49 years (range: 38–60 years). Mean tumor size was 8.9 cm (range: 3.0–15.5 cm). Mastectomy was performed in three cases. One patient had axillary nodal metastasis. All underwent chemotherapy and three received radiation therapy after surgery. CONCLUSIONS: With a mean follow-up of 36 months (range: 10–60 months), one case had a tumor recurrence (25%). Three patients (75%) died from metastatic disease and one (25%) is still alive and free of disease.

Spindle Cell Metaplastic Breast Carcinoma

Introduction: Metaplastic breast carcinoma is an uncommon malignancy that constitutes < 5% of all breast cancers. There are 5 subtypes which are spindle cell, squamous cell, carcinosarcoma, matrix-producing and metaplastic with osteoclastic giant cells. Spindle cell carcinoma represents approximately <0.3% of invasive breast carcinomas. It is typically a triple-negative cancer with distinct pathological characteristics, but relatively a non-conclusive imaging findings. Case report: An elderly lady presented with an enlarging painful left breast lump for 1 year. Palpable left breast lump noted on clinical examination. Mammography demonstrated a high density, oval lesion with a partially indistinct margin. Corresponding ultrasound showed a large irregular heterogeneous lesion with solid-cystic areas. Histopathology showed atypical spindle-shaped cells which stained positive for cytokeratins and negative for hormone and human epidermal growth factor receptors, which favours spindle cell metaplastic carcinoma. Left mastectomy and axillary dissection were performed, and the final diagnosis was consistent with metaplastic spindle cell carcinoma. Conclusion: Spindle cell carcinoma of the breast is a rare aggressive histological type of carcinoma which may present with benign features on imaging. Tissue diagnosis is essential for prompt diagnosis with multidisciplinary team discussion to guide management and improve patient’s outcome.

Malignant Phyllodes Tumor: Imaging Features With Histopathologic Correlation

Phyllodes tumors (PT) are rare fibroepithelial lesions of the breast that commonly present as rapidly enlarging, palpable masses. Phyllodes tumors may be classified as benign, borderline, or malignant on the basis of histopathologic analysis. Although malignant PT cannot be distinguished from benign PT on the basis of imaging findings alone, studies suggest that malignant PT tend to be larger and irregular in shape, and they are less likely to have circumscribed margins. If biopsy results are indeterminate, excisional biopsy should be performed. Malignant PT can be difficult to distinguish histologically from sarcomas and spindle cell metaplastic breast carcinoma; the distinction is important for prognosis and treatment. Malignant PT are treated surgically with wide local excision, without a clear role for adjuvant radiation or chemotherapy in most cases. Nearly one-third of malignant PT recur locally, usually within a few years after initial diagnosis. Distant metastatic disease is rare, and the five-year overall survival rate of malignant PT is close to 80%. The purpose of this article is to review the clinical presentation, imaging appearance, histopathology, and management of malignant PT.

In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types

Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell–matrix interactions in rare cancer types using higher passage PDX tissue.

Poor response to neoadjuvant chemotherapy in metaplastic breast carcinoma

Metaplastic breast carcinoma (MpBC) is a rare special histologic subtype of breast carcinoma characterized by the presence of squamous and/or mesenchymal differentiation. Most MpBCs are of triple-negative phenotype and neoadjuvant chemotherapy (NAC) is frequently utilized in patients with MpBC. The aim of this study was to evaluate response to NAC in a retrospective cohort of MpBCs. We identified 44 patients with MpBC treated with NAC at our center between 2002 and 2018. Median age was 48 years, 86% were clinical stage II–III, and 36% were clinically node-positive. Most (80%) MpBCs were triple-negative or low (1–10%) hormonal receptor positive and HER2 negative on pre-NAC biopsy. While on NAC, 49% showed no clinical response or clinico-radiological progression. Matrix-producing subtype was associated with clinico-radiological response (p = 0.0036). Post NAC, two patients initially ineligible for breast-conserving surgery (BCS) were downstaged to be eligible for BCS, whereas three patients potentially eligible for BCS before treatment became ineligible due to disease progression. Only one (2%) patient had a pathologic complete response (pCR). Among the 16 patients presenting with biopsy-proven clinical node-positive disease, 3 (19%) had nodal pCR. Axillary lymph node dissection was avoided in 3 (19%) patients who had successful axillary downstaging. Residual cancer burden (RCB) was assessed in 22 patients and was significantly associated with disease-free survival and overall survival. We observed a poor response or even disease progression on NAC among patients with MpBC, suggesting that NAC should be reserved for patients with inoperable MpBC.

Epithelial Mesenchymal Transition and Immune Response in Metaplastic Breast Carcinoma

Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent triple negative (TN) invasive carcinomas with poor prognosis. MBCs have a different clinical behavior from other types of triple negative breast cancer (TNBC), being more resistant to standard chemotherapy. MBCs are an example of tumors with activation of epithelial–mesenchymal transition (EMT). The mechanisms involved in EMT could be responsible for the increase in the infiltrative and metastatic capacity of MBCs and resistance to treatments. In addition, a relationship between EMT and the immune response has been seen in these tumors. In this sense, MBC differ from other TN tumors showing a lower number of tumor-infiltrating lymphocytes (TILS) and a higher percentage of tumor cells expressing programmed death-ligand 1 (PD-L1). A better understanding of the relationship between the immune system and EMT could provide new therapeutic approaches in MBC.

Clinicopathologic Characteristics and Outcome Descriptors of Metaplastic Breast Carcinoma

Context.— Metaplastic breast carcinoma is an aggressive form of breast cancer that accounts for 0.5% to 3% of all breast cancers. Objective.— To study the clinicopathologic characteristics and outcomes of this rare disease. Design.— Retrospective study of patients with a diagnosis of metaplastic breast carcinoma between 2000 and 2019. Hematoxylin-eosin–stained slides were reviewed and additional clinical data were obtained from electronic medical records. Univariable and multivariable Cox proportional hazard regression analyses were used to determine associations between overall survival and several clinicopathologic variables. Results.— Of the 125 patients with metaplastic breast carcinoma identified, only patients with high-grade disease (N = 115) were included in the data analysis. A total of 38 participants (33%) were white, 66 (57%) were African American, and 11 (10%) belonged to other ethnicities. The median age at diagnosis was 57 years. The median tumor size was 3 cm. Heterologous histology was seen in 30% of cases. Multivariable analyses showed that patients with a larger tumor size had worse overall survival (hazard ratio [HR], 1.25; 95% CI, 1.10–1.44; P &lt; .001). Distant metastatic disease was also associated with worse overall survival on multivariable analysis (HR, 10.27; 95% CI, 2.03–55.54; P = .005). In addition to treatment with either partial or complete mastectomies, 84 patients (73%) received chemotherapy. Multivariable analyses showed that chemotherapy had no effect on overall survival (HR, 0.53; 95% CI, 0.09–6.05; P = .55). Conclusions.— A larger tumor size and distant metastatic disease are associated with worse overall survival in patients with metaplastic breast carcinoma. Additional studies are needed to further characterize our findings.