Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

Reed, Amy E. McCart; Kalinowski, Lauren; Simpson, Peter T.; Lakhani, Sunil R.

doi:10.1186/s13058-020-01384-6

Cited by 89 publications

(81 citation statements)

References 130 publications

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“…The Global Cancer Statistics reported that female breast cancer (BC) surpassed lung cancer as the most diagnosed cancer, with an estimated 2.3 million new cases (11.7%) (Sung et al, 2021). BC is generally regarded as a heterogeneous disease in terms of its molecular features, histological composition, and clinical characteristics (McCart Reed et al, 2021;Sadeghalvad et al, 2021). With the evolution of high-throughput technologies, we tend to subtype the disease into clinically relevant molecular subtypes, including normal-like, luminal A and B, HER2-enriched, and basallike or more intrinsic subtypes (Ochoa et al, 2020;Morgan et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer

Zhang

Shan

Lin

et al. 2021

Front. Cell Dev. Biol.

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Breast cancer (BC) represents a molecularly and clinically heterogeneous disease. Recent progress in immunotherapy has provided a glimmer of hope for several BC subtypes. The relationship between N6-methyladenosine (m6A) modification and long non-coding RNAs (LncRNAs) is still largely unexplored in BC. Here, with the intention to dissect the landscape of m6A-related lncRNAs and explore the immunotherapeutic value of the m6A-related lncRNA signature, we identified m6A-related lncRNAs by co-expression analysis from The Cancer Genome Atlas (TCGA) and stratified BC patients into different subgroups. Furthermore, we generated an m6A-related lncRNA prognostic signature. Four molecular subtypes were identified by consensus clustering. Cluster 3 preferentially had favorable prognosis, upregulated immune checkpoint expression, and high level of immune cell infiltration. Twenty-one m6A-related lncRNAs were applied to construct the m6A-related lncRNA model (m6A-LncRM). Survival analysis and receiver operating characteristic (ROC) curves further confirmed the prognostic value and prediction performance of m6A-LncRM. Finally, high- and low-risk BC subgroups displayed significantly different clinical features and immune cell infiltration status. Overall, our study systematically explored the prognostic value of the m6A-related LncRNAs and identified a high immunogenicity BC subtype. The proposed m6A-related LncRNA model might serve as a robust prognostic signature and attractive immunotherapeutic targets for BC treatment.

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Section: Introductionmentioning

confidence: 99%

Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer

Zhang

Shan

Lin

et al. 2021

Front. Cell Dev. Biol.

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“…As described by early cohort studies ( [12][13][14], reviewed in [8,15]), the most commonly altered driver mutations in ILC are in CDH1, TP53, PIK3CA, FOXA1, PTEN, TBX3, FGFR2, ERBB2, and ERBB3. AKT1 and CTNNA1 are increasingly important in ILC [16,17]; however, relatively low mutation frequencies were detected when profiled.…”

Section: Mutation Profiles Of Ilcmentioning

confidence: 99%

“…High resolution ILC genomic research has emerged over the last five years (reviewed in [8]), and the value of ILC sub-studies in clinical trials is undoubted. In order to facilitate detailed analysis of ILC, in the context of precision oncology, we present a meta-analysis of available ILC genomic datasets to develop a unified resource to inform further essential ILC research.…”

Section: Introductionmentioning

confidence: 99%

The Genomic Landscape of Lobular Breast Cancer

Reed

Foong

Kutasovic

et al. 2021

Cancers

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Invasive lobular carcinoma (ILC) is the second most common breast cancer histologic subtype, accounting for approximately 15% of all breast cancers. It is only recently that its unique biology has been assessed in high resolution. Here, we present a meta-analysis of ILC sequencing datasets, to provide a long-awaited ILC-specific resource, and to confirm the prognostic value and strength of association between a number of clinico-pathology features and genomics in this special tumour type. We consider panel (n = 684), whole exome (n = 215) and whole genome sequencing data (n = 48), and review histology of The Cancer Genome Atlas cases to assign grades and determine whether the ILC is of classic type or a variant, such as pleomorphic, prior to performing statistical analyses. We demonstrate evidence of considerable genomic heterogeneity underlying a broadly homogeneous tumour type (typically grade 2, estrogen receptor (ER)-positive); with genomes exhibiting few somatic mutations or structural alterations, genomes with a hypermutator phenotype, and tumours with highly rearranged genomes. We show that while CDH1 (E-cadherin) and PIK3CA mutations do not significantly impact survival, overall survival is significantly poorer for patients with a higher tumour mutation burden; this is also true for grade 3 tumours, and those carrying a somatic TP53 mutation (and these cases were more likely to be ER-negative). Taken together, we have compiled a meta-dataset of ILC with molecular profiling, and our analyses show that the genomic landscape significantly impacts the tumour’s variable natural history and overall survival of ILC patients.

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“…Recent studies have shed new light on ILC's different biology, clinical presentation, disease behavior, and metastasis [11,13,14]. Findings include differences in enriched molecular features in lobular tumors that could lead to future targeted therapies [15][16][17][18][19].…”

Section: Historic View Of Lobular Carcinoma Is Challenged By New Evidencementioning

confidence: 99%

How Researchers, Clinicians and Patient Advocates Can Accelerate Lobular Breast Cancer Research

Pate

Desmedt

Metzger

et al. 2021

Cancers

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Breast cancer research and therapies have significantly advanced in recent years. However, Invasive Lobular Carcinoma (ILC), the second most common histological type of breast cancer and the sixth most frequently diagnosed cancer of women, has not always benefited from critical analysis, missing opportunities to better understand this important subtype. Recent progress understanding the biological and behavioral differences of ILC demonstrates that it is a unique subtype of breast cancer which can respond differently to common therapies. These new insights have increased interest in researching lobular breast disease. Concurrently, the formation of motivated patient-led advocacy organizations working in partnership with basic, translational and clinical researchers creates new opportunities, including connecting a dispersed patient population to research, encouraging new research funding and connecting patient advocates to researchers to advance common goals. This commentary will explore the unprecedented opportunity to drive multidisciplinary, multicenter and international collaborative research into lobular breast cancer that builds on recent research progress. Collaborative research partnerships that include advocates can result in a better understanding of ILC, identify targeted therapies and refine standard of care therapies that are currently equally applied to all breast cancers, resulting in improvements in the diagnosis, treatment and follow-up care for patients with ILC.

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Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

Cited by 89 publications

References 130 publications

Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer

Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer

The Genomic Landscape of Lobular Breast Cancer

How Researchers, Clinicians and Patient Advocates Can Accelerate Lobular Breast Cancer Research

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