Complete Response of Chemo-Refractory Metastatic Metaplastic Breast Cancer to Paclitaxel-Immunotherapy Combination

Sayed, Adher D. Al; Elshenawy, Mahmoud A; Tulbah, Asma; Al‐Tweigeri, Taher; Ghebeh, Hazem

doi:10.12659/ajcr.918770

Cited by 31 publications

(20 citation statements)

References 23 publications

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“…17 Similarly, Al Sayed et al reported a complete response to the combination of a novel anti-PD-L1 antibody, durvalumab, with paclitaxel in a patient with chemoresistant, metastatic MBC whose neoplastic cells overexpressed PD-L1. 41 In our study, 2 PD-L1-positive (one in TC and IC, respectively) spindle cell carcinomas harbored PTEN mutations. PTEN mutations in cancer cells may induce immunosuppressive expression signatures and the lack of response to anti-PD-1 therapies.…”

Section: Semir Vranic Et Almentioning

confidence: 47%

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers

Vranić

Stafford

Palazzo

et al. 2020

Clinical Breast Cancer

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Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative phenotype. Twenty-three spindle cell carcinomas were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but, owing to the lack of uniform findings, individual patient profiling is necessary. Introduction: Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It is associated with a marked resistance to conventional chemotherapy and has an overall poor outcome. Materials and Methods: Twenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. Results: The majority (21/23) of spindle cell carcinomas were TNBC. Estrogen and androgen receptor expression above the therapeutic thresholds were detected in 2 cases each. Pathogenic gene mutations were identified in 21 of 23 cases, including PIK3CA, TP53, HRAS, NF1, and PTEN. One case with matched pre-and postchemotherapy samples exhibited a consistent mutational profile (PIK3CA and HRAS mutations) in both samples. Gene amplifications were present in 5 cases, including 1 case without detectable mutations. The spindle cell carcinomas cohort had consistently low total mutational burden (all below the 80th percentile for the entire TNBC cohort). All tumors were microsatellite stable. Programmed death-ligand 1 expression was observed on both tumor cells (in 7/21 cases), and in tumor-infiltrating immune cells (2/21 cases). Conclusions: Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but owing to the lack of uniform findings, individual patient profiling is necessary. Detection of individual combinations of biomarkers should improve treatment options for this rare but aggressive disease.

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Section: Semir Vranic Et Almentioning

confidence: 47%

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers

Vranić

Stafford

Palazzo

et al. 2020

Clinical Breast Cancer

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“…Anecdotic observations have demonstrated that some MBC can respond to check-point inhibitors. Thus, Adams et al [ 81 ] and Al Sayed et al [ 82 ] reported complete responses to pembrolizumab and durvalumab, respectively, in two patients with advanced MBC with PD-L1 tumor cell expression. The DART study (NCT02834013) evaluates dual anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab) blockade in rare tumors, including an MBC cohort (Arm 36) [ 11 ].…”

Section: Targeted Therapy In Mbcmentioning

confidence: 99%

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

González-Martínez

Pérez-Míes

Carretero‐Barrio

et al. 2020

Cancers

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Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent invasive carcinomas that display differentiation of the neoplastic epithelium towards squamous cells and/or mesenchymal-type elements. Most MBC have a triple negative phenotype and poor prognosis. Thus, MBC have worse survival rates than other invasive breast carcinomas, including other triple negative breast carcinomas (TNBC). In this study, we reviewed the molecular features of MBC, pointing out the differences among subtypes. The most frequently mutated genes in MBC were TP53 and PIK3CA. Additionally, mutations in the other genes of the PI3K/AKT pathway indicated its importance in the pathogenesis of MBC. Regarding copy number variations (CNVs), MYC was the most frequently amplified gene, and the most frequent gene loss affected the CDKN2A/CDKN2B locus. Furthermore, the pattern of mutations and CNVs of MBC differed from those reported in other TNBC. However, the molecular profile of MBC was not homogeneous among histological subtypes, being the alterations in the PI3K pathway most frequent in spindle cell carcinomas. Transcriptomic studies have demonstrated an epithelial to mesenchymal program activation and the enrichment of stemness genes in most MBC. In addition, current studies are attempting to define the immune microenvironment of these tumors. In conclusion, due to specific molecular features, MBC have a different clinical behavior from other types of TNBC, being more resistant to standard chemotherapy. For this reason, new therapeutic approaches based on tumor molecular characteristics are needed to treat MBC.

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“… 46 A similar combination of durvalumab (anti-PD-L1) and paclitaxel was also shown to provide a sustained, complete response in a second case report of advanced MpBC, this time with squamous features. 47 In this case, 20% of tumor cells stained with medium intensity (clone SP142), and there was an absence of staining in the TILS; while in the former case, 100% of tumor cells stained positively for PD-L1 using the 22C3 clone. Indeed, there is no standardized definition criteria for PD-L1 staining at this stage, and the characterization of expression of this and other immune checkpoint markers across TNBC and MpBC has only recently emerged.…”

Section: Precision Oncology For Mpbcmentioning

confidence: 67%

An Update on the Molecular Pathology of Metaplastic Breast Cancer

Reed

Kalaw

Lakhani

2021

BCTT

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Metaplastic breast cancer (MpBC) is a fascinating morphologic sub-type of breast cancer, characterised by intra-tumoural heterogeneity. By definition, these tumors show regions of metaplasia that can present as spindle, squamous, chondroid or even osseous differentiation. MpBC are typically triple-negative, and are therefore not targetable with hormone therapy or anti-HER2 therapies, leaving only chemotherapeutics for management. MpBC are known for their aggressive course and poor response to chemotherapy. We review herein the pathology and molecular landscape of MpBC and discuss opportunities for targetted therapies as well as immunotherapies.

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Complete Response of Chemo-Refractory Metastatic Metaplastic Breast Cancer to Paclitaxel-Immunotherapy Combination

Cited by 31 publications

References 23 publications

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

An Update on the Molecular Pathology of Metaplastic Breast Cancer

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