scholarly journals Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1598 ◽  
Author(s):  
Giovanni Corso ◽  
Giacomo Montagna ◽  
Joana Figueiredo ◽  
Carlo La Vecchia ◽  
Uberto Fumagalli Romario ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Family History ◽  
Incidental Finding ◽  
Positive Family History ◽  
Diffuse Gastric Cancer ◽  
Clinical Approach ◽  
Clinical Criteria ◽  
History Of ◽  
E Cadherin

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC).

Prevalence of CDH1 germline mutations in subjects with early onset or familial lobular breast cancer, a multicenter collaboration

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11042-11042
Author(s):  
S. Masciari ◽  
K. A. Schrader ◽  
J. Senz ◽  
N. Tung ◽  
J. Balmana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Family History ◽  
Early Onset ◽  
Direct Sequencing ◽  
Familial Cancer ◽  
Germline Mutations ◽  
Diffuse Gastric Cancer ◽  
Prophylactic Gastrectomy ◽  
History Of

11042 Background: Invasive lobular breast carcinoma (LBC) is part of the hereditary diffuse gastric cancer (HDGC) syndrome, associated with germline mutations in the E-cadherin (CDH1) gene. CDH1 mutations can be identified in 80% of families ascertained by DGC. The risk of DGC in CDH1 mutation carriers is 67% in males, and 83% in females; the estimated risk of LBC in women is 39–50% to age 80. Management of HDGC includes prophylactic gastrectomy. In this study, we estimated the prevalence of germline CDH1mutations among women with LBC who were either diagnosed at young age or had family history of breast cancer (BC). Methods: Germline DNA was collected from 383 women with LBC or mixed, lobular/ductal, BC from breast cancer programs, familial cancer clinics, and population-based cohorts. Germline BRCA1or BRCA2mutations carriers were excluded. Eligible women had (1) LBC before age 45 or (2) LBC at any age with at least two 1st or 2nd degree relatives with BC of any type. Denaturing high pressure liquid chromatography was undertaken, followed by direct sequencing of exons displaying changes. Results: At the time of submission 310 of 383 samples have been fully sequenced. One previously characterized missense mutation and four novel non-synonymous variants (1.6%) were found. Three of these women had LBC before 45 years and no family history of BC; two had BC family history. No gastric cancers were reported in these families. Functional assays to assess the pathogenicity of the variants are in process. Conclusions: These results confirm that CDH1 is responsible for a small proportion of familial and early onset LBC. Given the difficulty of identifying CDH1 mutations from BC history alone and the importance of managing the gastric cancer risk in CDH1carriers, these findings should underscore the need to obtain an accurate abdominal cancer family history from women with LBC. No significant financial relationships to disclose.

scholarly journals Clinical spectrum and pleiotropic nature of CDH1 germline mutations

2019 ◽  
Vol 56 (4) ◽  
pp. 199-208 ◽  
Author(s):  
Joana Figueiredo ◽  
Soraia Melo ◽  
Patrícia Carneiro ◽  
Ana Margarida Moreira ◽  
Maria Sofia Fernandes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Genetic Alterations ◽  
Tumour Suppressor Gene ◽  
Diffuse Gastric Cancer ◽  
Loss Of Function ◽  
Lobular Breast Cancer ◽  
Cancer Syndrome ◽  
Risk Of Cancer ◽  
E Cadherin

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.

A Group Therapy Approach to Facilitate Integration of Risk Information for Women at Risk for Breast Cancer

1998 ◽  
Vol 43 (4) ◽  
pp. 375-380 ◽  
Author(s):  
Mary Jane Esplen ◽  
Brenda Toner ◽  
Jonathan Hunter ◽  
Gordon Glendon ◽  
Kate Butler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Family History ◽  
Group Therapy ◽  
Perceived Risk ◽  
Positive Family History ◽  
Risk Information ◽  
Degree Relative ◽  
Therapy Approach ◽  
History Of

Objective: To describe and illustrate elements of a group counselling approach designed to enhance the communication of risk information on breast cancer (BC) to women with a family history of this disease. Breast cancer is a leading cause of female cancer death. The most important risk factor for BC is a positive family history in at least 1 first-degree relative, and approximately one-third of women with BC have a family history of the disease. Recent evidence suggests that there is a significant psychological impact associated with having a family history of BC, and this may influence the psychological adjustment and response to being counselled for personal risk. New counselling approaches are required. Method: This paper describes a group therapy approach that incorporates principles of supportive-expressive therapy designed to address the emotional impact of being at risk for BC and to promote accuracy of perceived risk. The key elements of the intervention are described along with clinical illustrations from groups that are part of an ongoing study to develop and standardize the group therapy. Conclusion: Qualitative data from the groups suggest that this model of therapy is both feasible and effective.

scholarly journals Male Breast Cancer: Surgical and Genetic Features and a Multidisciplinary Management Strategy

Breast Care ◽  
2019 ◽  
Vol 15 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Francesca Pellini ◽  
Eleonora Granuzzo ◽  
Silvia Urbani ◽  
Sara Mirandola ◽  
Marina Caldana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
High Risk ◽  
Male Breast Cancer ◽  
Brca2 Mutation ◽  
Positive Family History ◽  
Male Breast ◽  
Mutation Carriers ◽  
History Of ◽  
Clinical Records

Background: Male breast cancer (MBC) is a rare disease with a rising incidence trend. The major risk factors related to MBC are a positive family history of breast cancer (BC) and BRCA1/2 mutations, which indicate a relevant genetic role. Methods: In this retrospective series, we enrolled 69 male patients presenting with male breast cancer (MBC) between 01/01/1992 and 31/12/2018, and 26 high-risk not-affected men presenting between 01/01/2016 and 31/12/2018. Participants’ electronic clinical records were reviewed. Patients’ data reported age at diagnosis, tumor characteristics, therapeutic management, and BRCA1/2 status as well as a family history of breast, ovarian, or prostate cancer (PCa) in first-degree relatives. Results: We analyzed 69 MBC patients. Median age was 64 years. The majority of tumors diagnosed were of an early TNM stage. The most frequent histological subtype was invasive ductal carcinoma (76.7%). Hormone receptors were positive in >90% of MBC cases. Nearly all patients underwent modified radical mastectomy or total mastectomy. Adjuvant endocrine therapy was delivered in 59.4%. Among MBC-affected patients, we recorded a high percentage of a positive family history of BC. Mutational analysis for the BRCA1/2 genes was performed in 17 MBC patients; 11.8% were carriers of BRCA2 pathogenic mutations. Among 26 healthy high-risk subjects included in this case series, 4 were BRCA1 mutation carriers and 9 were BRCA2 mutation carriers. Discussion: We evaluated the distribution of clinicopathological characteristics in MBC subjects and assessed the frequency of mutations in the BRCA genes in affected patients and healthy high-risk subjects, with the aim of proposing a surveillance program for BC and PCa.

A retrospective study on breast cancer presentation, risk factors, and protective factors in patients with a positive family history of breast cancer

2020 ◽  
Vol 26 (3) ◽  
pp. 469-473
Author(s):  
Ying Yi Liaw ◽  
Foong Shiang Loong ◽  
Suzanne Tan ◽  
Sze Yun On ◽  
Evelyn Khaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Retrospective Study ◽  
Family History ◽  
Protective Factors ◽  
Positive Family History ◽  
History Of

Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect

2018 ◽  
Vol 55 (7) ◽  
pp. 431-441 ◽  
Author(s):  
Giovanni Corso ◽  
Joana Figueiredo ◽  
Carlo La Vecchia ◽  
Paolo Veronesi ◽  
Gabriella Pravettoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Age At Onset ◽  
Genetic Defect ◽  
Prophylactic Surgery ◽  
Current Evidence ◽  
Diffuse Gastric Cancer ◽  
Lobular Breast Cancer ◽  
Clinicopathological Findings ◽  
History Of

Recent studies have reported germline CDH1 mutations in cases of lobular breast cancer (LBC) not associated with the classical hereditary diffuse gastric cancer syndrome. A multidisciplinary workgroup discussed genetic susceptibility, pathophysiology and clinical management of hereditary LBC (HLBC). The team has established the clinical criteria for CDH1 screening and results’ interpretation, and created consensus guidelines regarding genetic counselling, breast surveillance and imaging techniques, clinicopathological findings, psychological and decisional support, as well as prophylactic surgery and plastic reconstruction. Based on a review of current evidence for the identification of HLBC cases/families, CDH1 genetic testing is recommended in patients fulfilling the following criteria: (A) bilateral LBC with or without family history of LBC, with age at onset <50 years, and (B) unilateral LBC with family history of LBC, with age at onset <45 years. In CDH1 asymptomatic mutant carriers, breast surveillance with clinical examination, yearly mammography, contrast-enhanced breast MRI and breast ultrasonography (US) with 6-month interval between the US and the MRI should be implemented as a first approach. In selected cases with personal history, family history of LBC and CDH1 mutations, prophylactic mastectomy could be discussed with an integrative group of clinical experts. Psychodecisional support also plays a pivotal role in the management of individuals with or without CDH1 germline alterations. Ultimately, the definition of a specific protocol for CDH1 genetic screening and ongoing coordinated management of patients with HLBC is crucial for the effective surveillance and early detection of LBC.

scholarly journals Prevalence of germline TP53 mutation among early onset middle eastern breast cancer patients

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abdul Khalid Siraj ◽  
Tariq Masoodi ◽  
Rong Bu ◽  
Sandeep Kumar Parvathareddy ◽  
Kaleem Iqbal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Middle Eastern ◽  
Mutation Screening ◽  
Univariate Analysis ◽  
Positive Family History ◽  
Germline Mutations ◽  
Pathogenic Mutations ◽  
History Of

Abstract Background The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited. Methods We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing. Results Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS. Conclusions TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.

scholarly journals BREAST CANCER;

2014 ◽  
Vol 21 (06) ◽  
pp. 1128-1132
Author(s):  
Abeer Nisar ◽  
M Naim Siddiqi ◽  
Naveed ur Rehman ◽  
Raza ur Rahman
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Family History ◽  
Menopausal Status ◽  
Positive Family History ◽  
American Woman ◽  
Breast Cancer Patients ◽  
Civil Hospital ◽  
Early Menarche ◽  
History Of

Objective: To assess the risk factors for breast cancer in patients attending oncology OPD of civil hospital Karachi, Pakistan. Introduction: Breast cancer is the single largest cause of death among women1,2. The probability of American woman developing breast cancer in their life is 7 in 11. Studies from subcontinent show that the incidence of breast cancer is increasing, with an estimated 80,000 new cases diagnosed annually. Breast cancer is the second most common type of cancer after lung cancer in Pakistan and ranked first in women. Only 10% women are diagnosed, out of them, 75% women do not get treatment and die within 5 years6. Data from Pakistan about the risk factors or association is not only scanty but also does not comment on the use of fatty diet in breast cancer patients. Method: A cross-sectional descriptive study conducted at Oncology OPD of civil hospital Karachi (CHK) from October 2009 -April 2011. One Hundred and Fifty consecutive patients having histopathalogical diagnosis of breast cancer were assessed for different risk factors that included marital status, parity, age, menopausal status, family history of breast cancer, prolong use of oral contraceptives, breast feeding, , early menarche, trauma to the breast and fatty diet. Result: Mean age of patients was 48 years. Three fourth (73%) of these female were above the age of 40 years. Consumption of fatty diet was found in 62.67% while positive family history of breast cancer was present in 34% of the cases. Early menarche and being nulliparous were not as strong risk factors as in previous studies. Conclusions: Our study has highlighted the need of further exploration in this area that would not only help this population but also enhance our understanding of different risk factors. This will have important implications for the overall management of breast cancer.

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