Genomic characterization and tumor evolution in paired samples of metaplastic breast carcinoma

Stradella, Agostina; Gargallo, Pablo; Cejuela, Mónica; Petit, Audrey; Bosch-Schips, Jan; Carbonell, Paula; Recalde, Sabela; Vethencourt, Andrea; Fernández-Ortega, Adela; Falo, Catalina; Gil-Gil, Miguel; Vázquez, Silvia; Obadia, Veronica; Villanueva-Vázquez, Rafael; Soler-Monsó, Teresa; Calabria, Inés; Pernas, Sònia

doi:10.1038/s41379-022-01017-7

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…Several clinical trials (NCT02834013, NCT02752685) using anti-PD-1/PD-L1 antibodies in advanced MpBC patients have achieved explicit survival benefits [ 54 , 55 ]. Other studies have proved that TERT promoter hotspot mutations [ 56 ] and the RPL39 A14V mutations [ 57 ] occur at high frequency in MpBC, and MYC amplification is highly enriched after metastasis [ 58 ]. These may become potential targets for treating MpBC in the future.…”

Section: Discussionmentioning

confidence: 99%

The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer

Lang

Zhao

et al. 2023

Breast Cancer Res Treat

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Objective Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients. Methods We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients. Results A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171–2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357–3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms. Conclusions MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.

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Section: Discussionmentioning

confidence: 99%

The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer

Lang

Zhao

et al. 2023

Breast Cancer Res Treat

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“…In this study, 65% of cases harbored TP53 gene alteration and the MRD-positive group had higher TP53 mutations than the MRD-negative group (83% vs. 61%, P=0.087), which is consistent with the worse prognosis among MRD-positive patients in the previous study. In addition, the MRD-positive group had a higher frequency of MYC amplification than the MRD-negative group (44% vs. 25%, P=0.109), which is also associated with high recurrence risk or metastasis in breast cancer ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

The ctDNA-based postoperative molecular residual disease status in different subtypes of early-stage breast cancer

Yang¹,

Zhang²,

Li³

et al. 2022

Gland Surg

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Background: Breast cancer is a highly heterogeneous disease. Early-stage, non-metastatic breast cancer is considered curable after definitive treatment. Early detection of tumor recurrence and metastasis through sensitive biomarkers is helpful for guiding clinical decision-making and early intervention in second-line treatment, which could improve patient prognosis and survival.Methods: In this real-world study, we retrospectively analyzed 82 patients with stages I to III breast cancer who had been analyzed by molecular residual disease (MRD) assay. A total of 82 tumor tissues and 224 peripheral blood samples were collected and detected by next-generation sequencing (NGS) based on a 1,021-gene panel in this study.Results: MRD positivity was detected in 18 of 82 patients (22.0%). The hormone receptor−/human epidermal growth factor receptor 2+ (HR−/HER2+) subgroup had the highest postoperative MRD detection rate at 30.8% (4/13). The BRCA2 and SLX4 genes were significantly enriched in all patients in the MRD positive group and FGFR1 amplification was significantly enriched in the MRD negative group with HR+/ HER2−. The number of single nucleotide variants (SNVs) in tissue samples of MRD-positive patients was higher than that of MRD-negative patients (11.94 vs. 8.50 SNVs/sample). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that there was a similar biological function of the tumormutated genes in the 2 MRD status groups.Conclusions: This real-world study confirmed that patient samples of primary tumor tissue with different MRD status and molecular subtypes had differential genetic features, which may be used to predict patients at high risk for recurrence.

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“…Metaplastic breast carcinomas have a high degree of genomic instability and display intricate patterns of copy number variations. 11 Compared with TNBC, MpBCs typically harbor significantly more mutations in TP53 (59% vs. 51%), PIK3CA (23% vs. 9%), and other members of the PI3K pathway (41% vs. 18%), 4 present genetic alterations in the Wnt pathway, 11,[15][16][17][18] and demonstrate CDKN2A loss, 11,19 EGFR overexpression and amplification, 11 MYC amplification, 20 TERT promoter hotspot mutations and gene amplification, 10,16,21 the enrichment of angiogenic genes, 22 and changes in genes related to the cell cycle 23 (Table 1). Furthermore, no differences between MpBCs and non-Mp TNBCs in the domains frequently mutated in either TP53 or PIK3CA, showing they have similar genetic alterations.…”

Section: Genetic Characteristicsmentioning

confidence: 99%

“…21 The majority of MYC amplifications is observed in relapse/progression samples compared with primary tumors. 20 The expression of 115 genes has been found to be significantly different between MpBCs and non-Mp TNBCs, with a considerable percentage of differentially expressed genes being associated with cell type identity. For instance, the expression of epithelial markers is significantly enriched in TNBCs, whereas MpBCs have a strong characteristic of mesenchymal gene expression.…”

Section: Genetic Characteristicsmentioning

confidence: 99%

A comprehensive overview of metaplastic breast cancer: Features and treatments

Yan,

Deng,

Zhang

2024

Cancer Science

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Metaplastic breast cancer is a rare, aggressive, and chemotherapy‐resistant subtype of breast cancers, accounting for less than 1% of invasive breast cancers, characterized by adenocarcinoma with spindle cells, squamous epithelium, and/or mesenchymal tissue differentiation. The majority of metaplastic breast cancers exhibit the characteristics of triple‐negative breast cancer and have unfavorable prognoses with a lower survival rate. This subtype often displays gene alterations in the PI3K/AKT pathway, Wnt/β‐catenin pathway, and cell cycle dysregulation and demonstrates epithelial–mesenchymal transition, immune response changes, TP53 mutation, EGFR amplification, and so on. Currently, the optimal treatment of metaplastic breast cancer remains uncertain. This article provides a comprehensive review on the clinical features, molecular characteristics, invasion and metastasis patterns, and prognosis of metaplastic breast cancer, as well as recent advancements in treatment strategies.

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Genomic characterization and tumor evolution in paired samples of metaplastic breast carcinoma

Cited by 5 publications

References 29 publications

The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer

The mixed subtype has a worse prognosis than other histological subtypes: a retrospective analysis of 217 patients with metaplastic breast cancer

The ctDNA-based postoperative molecular residual disease status in different subtypes of early-stage breast cancer

A comprehensive overview of metaplastic breast cancer: Features and treatments

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