Genomics and premalignant breast lesions: clues to the development and progression of lobular breast cancer

CDH1 encodes E-cadherin, a key protein in adherens junctions. Given that E-cadherin is involved in major cellular processes such as embryogenesis and maintenance of tissue architecture, it is no surprise that deleterious effects arise from its loss of function. E-cadherin is recognised as a tumour suppressor gene, and it is well established that CDH1 genetic alterations cause diffuse gastric cancer and lobular breast cancer—the foremost manifestations of the hereditary diffuse gastric cancer syndrome. However, in the last decade, evidence has emerged demonstrating that CDH1 mutations can be associated with lobular breast cancer and/or several congenital abnormalities, without any personal or family history of diffuse gastric cancer. To date, no genotype–phenotype correlations have been observed. Remarkably, there are reports of mutations affecting the same nucleotide but inducing distinct clinical outcomes. In this review, we bring together a comprehensive analysis of CDH1-associated disorders and germline alterations found in each trait, providing important insights into the biological mechanisms underlying E-cadherin’s pleiotropic effects. Ultimately, this knowledge will impact genetic counselling and will be relevant to the assessment of risk of cancer development or congenital malformations in CDH1 mutation carriers.

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Diffusion tensor imaging on 3-T MRI breast: diagnostic performance in comparison to diffusion-weighted imaging

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00473-6 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Dalia Abdelhady ◽

Amany Abdelbary ◽

Ahmed H. Afifi ◽

Alaa-eldin Abdelhamid ◽

Hebatallah H. M. Hassan

Keyword(s):

Breast Cancer ◽

Diffusion Tensor Imaging ◽

Sensitivity And Specificity ◽

Diffusion Weighted Imaging ◽

Diffusion Tensor ◽

Breast Mri ◽

Breast Lesions ◽

Dce Mri ◽

Additional Tool ◽

Diffusion Weighted

Abstract Background Breast cancer is the most prevalent cancer among females. Dynamic contrast-enhanced MRI (DCE-MRI) breast is highly sensitive (90%) in the detection of breast cancer. Despite its high sensitivity in detecting breast cancer, its specificity (72%) is moderate. Owing to 3-T breast MRI which has the advantage of a higher signal to noise ratio and shorter scanning time rather than the 1.5-T MRI, the adding of new techniques as diffusion tensor imaging (DTI) to breast MRI became more feasible. Diffusion-weighted imaging (DWI) which tracks the diffusion of the tissue water molecule as well as providing data about the integrity of the cell membrane has been used as a valuable additional tool of DCE-MRI to increase its specificity. Based on DWI, more details about the microstructure could be detected using diffusion tensor imaging. The DTI applies diffusion in many directions so apparent diffusion coefficient (ADC) will vary according to the measured direction raising its sensitivity to microstructure elements and cellular density. This study aimed to investigate the diagnostic accuracy of DTI in the assessment of breast lesions in comparison to DWI. Results By analyzing the data of the 50 cases (31 malignant cases and 19 benign cases), the sensitivity and specificity of DWI in differentiation between benign and malignant lesions were about 90% and 63% respectively with PPV 90% and NPV 62%, while the DTI showed lower sensitivity and specificity about 81% and 51.7%, respectively, with PPV 78.9% and NPV 54.8% (P-value ≤ 0.05). Conclusion While the DWI is still the most established diffusion parameter, DTI may be helpful in the further characterization of tumor microstructure and differentiation between benign and malignant breast lesions.

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Extended gene panel testing in lobular breast cancer

Familial Cancer ◽

10.1007/s10689-021-00241-5 ◽

2021 ◽

Author(s):

Elke M. van Veen ◽

D. Gareth Evans ◽

Elaine F. Harkness ◽

Helen J. Byers ◽

Jamie M. Ellingford ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Detection Rate ◽

Gene Panel ◽

Lobular Breast Cancer ◽

Germline Variants ◽

Panel Testing ◽

Pathogenic Variants ◽

Gene Panel Testing ◽

Increased Risk

AbstractPurpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

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Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

Nature Communications ◽

10.1038/s41467-021-25240-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Vidya C. Sinha ◽

Amanda L. Rinkenbaugh ◽

Mingchu Xu ◽

Xinhui Zhou ◽

Xiaomei Zhang ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Mouse Model ◽

Transition State ◽

Tumor Cell ◽

Single Cell ◽

Tumor Cells ◽

Breast Lesions ◽

Aggressive Tumor ◽

Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

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Contrast-enhanced ultrasound of breast fibromatosis: a case report

Journal of International Medical Research ◽

10.1177/03000605211010619 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052110106

Author(s):

Shanhong Lin ◽

Yong Cao ◽

Libin Chen ◽

Mei Chen ◽

Shengmin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Rare Case ◽

Common Type ◽

Breast Lesions ◽

Contrast Enhanced Ultrasound ◽

High Similarity ◽

Potential Value ◽

Contrast Enhanced ◽

Malignant Breast ◽

Contrast Enhanced Ultrasonography

We herein present a rare case of breast fibromatosis, the contrast-enhanced ultrasonography (CEUS) findings of which we believe have never been described. The high similarity between the clinical and imaging manifestations of breast cancer makes its differential diagnosis difficult. In this report, we describe the CEUS findings of a less common type of fibromatosis, discuss the potential value of CEUS to differentiate it from malignant breast lesions, and briefly review the literature.

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