Metaplastic breast carcinoma: a clinical-pathologic study of 97 cases with subset analysis of response to neoadjuvant chemotherapy

Han, Min; Salamat, Arsalan; Zhu, Li; Zhang, Huina; Clark, Beth Z.; Dabbs, David J.; Carter, Gloria J; Brufsky, Adam; Jankowitz, Rachel C.; Puhalla, Shannon; Johnson, R. R.; Soran, Atilla; Steiman, Jennifer; McAuliffe, Priscilla F.; Diego, Emilia; Bhargava, Rohit

doi:10.1038/s41379-019-0208-x

Cited by 73 publications

(99 citation statements)

References 20 publications

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“…We came to the hypothesis that patients with infiltrating ductal carcinoma or medullary carcinoma might be more sensitive to immunotherapy. However, metaplastic cancer, which is a rare subtype of breast cancer, is poorly responsive to neoadjuvant chemotherapy (28). Patients with metaplastic cancer may benefit from targeted therapy or radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Immune-Related Genes as Potential Marker of Prognosis in Breast Cancer

Geng

et al. 2020

Front. Oncol.

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The tumor microenvironment (TME) is a heterogeneous system that contributes to breast cancer progression. The Cancer Genome Atlas (TCGA) database provides global gene expression profiling data for further analysis of various malignancies, including breast cancer. Based on the ESTIMATE algorithm, immune and stromal scores were calculated according to immune or stromal components in the TME. We divided breast cancer cases into high-and low-score groups and identified differentially expressed genes (DEGs) that were significantly associated with overall survival. We performed enrichment analysis and constructed a protein-protein interaction network and found that the DEGs were mainly involved in primary immunodeficiency, T cell receptor signaling pathway and cytokine-cytokine receptor reaction. Furthermore, we explored the effect of aging on immune and stromal scores, which was validated by lower immune/stromal scores, lower infiltration of T cells and lower expression of immune checkpoints in the elder group. In conclusion, certain differentially expressed immune-related genes contribute to longer overall survival, and aging influences the immune microenvironment and immunotherapy efficacy by changing the tumor-infiltrating lymphocyte (TIL) abundance and checkpoint expression in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Alterations in Immune-Related Genes as Potential Marker of Prognosis in Breast Cancer

Geng

et al. 2020

Front. Oncol.

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“…MOUSE MODELS, AND BACK With the exception of low-grade adenosquamous carcinoma and fibromatosis-like metaplastic carcinoma, metaplastic breast carcinomas are more aggressive and demonstrate a higher propensity for metastasis than nonmetaplastic TNBCs. 2,31 These tumors are frequently chemoresistant, with variable responses to neoadjuvant chemotherapy [32][33][34] (Figure 2, A through C).…”

Section: New Promising Molecular Alterations In Metaplastic Carcinommentioning

confidence: 99%

Metaplastic Breast Carcinoma: Update on Histopathology and Molecular Alterations

McMullen

Zoumberos

Kleer

2019

Archives of Pathology &Amp; Laboratory Medicine

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Context— Metaplastic carcinoma is a rare, triple-negative carcinoma of the breast that exhibits transformation of part or all of its glandular carcinomatous component into a nonglandular, or metaplastic, component. The World Health Organization currently recognizes 5 variants of metaplastic carcinoma based on their histologic appearance. Objective— To review the histologic classifications, differential diagnosis, prognosis, and recent laboratory studies of metaplastic breast carcinoma. Data Sources.— We reviewed recently published studies that collectively examine metaplastic carcinomas, including results from our own research. Conclusions.— Metaplastic breast carcinoma has a broad spectrum of histologic patterns, often leading to a broad differential diagnosis. Diagnosis can typically be rendered by a combination of morphology and immunohistochemical staining for high-molecular-weight cytokeratins and p63. Recent studies elucidate new genes and pathways involved in the pathogenesis of metaplastic carcinoma, including the downregulation of CCN6 and WNT pathway gene mutations, and provide a novel MMTV-Cre; Ccn6fl/fl knockout disease-relevant mouse model to test new therapies.

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“…However, MBCs have a worse response to neoadjuvant systemic chemotherapy [9] regimens including doxorubicin and cyclophosphamide, or doxorubicin and 5-fluorouracil, in comparison to the overall response of these regimens to other invasive breast cancer subtypes [4,8,10]. The characteristic heterogeneity within MBC, exemplified by the diverse histologic subtypes of MBC, and the dramatically different response rates to chemotherapy of the subtypes [11], contribute to why this malignancy is difficult to manage therapeutically [2,12]. These findings emphasize the urgent necessity to identify novel therapeutic strategies that are specifically designed to target the unique and heterogeneous nature of MBC.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor

et al. 2020

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Metaplastic breast carcinoma (MBC) is a clinically aggressive and rare subtype of breast cancer, with similar features to basal-like breast cancers. Due to rapid growth rates and characteristic heterogeneity, MBC is often unresponsive to standard chemotherapies; and novel targeted therapeutic discovery is urgently needed. Histone deacetylase inhibitors (DACi) suppress tumor growth and metastasis through regulation of the epithelial-to-mesenchymal transition axis in various cancers, including basal-like breast cancers. We utilized a new MBC patient-derived xenograft (PDX) to examine the effect of DACi therapy on MBC. Cell morphology, cell cycle-associated gene expressions, transwell migration, and metastasis were evaluated in patient-derived cells and tumors after treatment with romidepsin and panobinostat. Derivations of our PDX model, including cells, spheres, organoids, explants, and in vivo implanted tumors were treated. Finally, we tested the effects of combining DACi with approved chemotherapeutics on relative cell biomass. DACi significantly suppressed the total number of lung metastasis in vivo using our PDX model, suggesting a role for DACi in preventing circulating tumor cells from seeding distal tissue sites. These data were supported by our findings that DACi reduced cell migration, populations, and expression of mesenchymal-associated genes. While DACi treatment did affect cell cycle-regulating genes in vitro, tumor growth was not affected compared to controls. Importantly, gene expression results varied depending on the cellular or tumor system used, emphasizing the importance of using multiple derivations of cancer models in preclinical therapeutic discovery research. Furthermore, DACi sensitized and produced a synergistic effect with approved oncology PLOS ONE |

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Metaplastic breast carcinoma: a clinical-pathologic study of 97 cases with subset analysis of response to neoadjuvant chemotherapy

Cited by 73 publications

References 20 publications

Alterations in Immune-Related Genes as Potential Marker of Prognosis in Breast Cancer

Alterations in Immune-Related Genes as Potential Marker of Prognosis in Breast Cancer

Metaplastic Breast Carcinoma: Update on Histopathology and Molecular Alterations

Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor

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