Phenotype and Prognosis of Patients With Breast Cancer and Pathogenic Variants of TP53

NCT04966923 | Completed

• 1 other identifier: 3.0840453
• Study Type: observational
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective and retrospective cohort study of patients with a documented pathogenic or likely pathogenic variants of TP53 were identified using blood DNA colection and breast cancer diagnosis by histological confirmation, between 1999 and 2022. All patients were followed by the Hereditary Group of a single cancer center (Instituto do Cancer do Estado de Sao Paulo). Patients were included if they had a histopathological diagnosis of localized invasive carcinoma or in situ carcinoma of the breast and with localized disease. Patients met Revised Chompret criteria, Li Fraumeni like syndrome,family member of carrier TP53 or hereditary breast and ovarian syndrome for germline test.

Conditions

Breast Cancer; TP53 R337H; Li-Fraumeni Syndrome; Prognosis Breast Cancer

Keywords

Breast Cancer; TP53

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  progression free survival from specific breast cancer from patients with BC and TP53. mutation versus BC and no pathogenic variants documented in genetic test. gnosed for each case included we will be selected 2 controls resulting in 90 control patients, for control are estimated with the same age (range 10 years), staging and immunohistochemistry

  We proposed 45 cases TP53 pathogenic carriers and breast cancer diagnosed for each case included we will be selected 2 controls resulting in 90 control patients, for control are estimated with the same age (range 10 years)

Secondary Outcomes (1)

• Overall Survival, causes of deaths, local breast cancer recurrence and contra-lateral breast cancer recurrence

  This study will enrollment 45 cases TP53 pathogenic carriers and breast cancer diagnosed for each case included we will be selected 2 controls resulting in 90 control patients, for control are estimated with the same age (range 10 years)

Study Arms (2)

Breast Cancer and documented pathogenic variant TP53

Documented pathogenic or likely pathogenic variants of TP53 were identified using blood DNA colection and localized breast cancer diagnosis by histological confirmation. All patients met Revised Chompret criteria or Li Fraumeni like syndrome or family member of carrier TP53

Other: No intervention in this study

Breast Cancer and no documented pathogenic variants in genetic test

Control group with localized breast cancer and no pathogenic variants documented in a genetic test

Other: No intervention in this study

Interventions

No intervention in this study OTHER

Analyses of pathogenic variant TP53 and variants in genetic test

Breast Cancer and documented pathogenic variant TP53; Breast Cancer and no documented pathogenic variants in genetic test

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

A prospective and retrospective cohort study of patients with a documented pathogenic or likely pathogenic variants of TP53 were identified using blood DNA colection and breast cancer diagnosis by histological confirmation, between 1999 and 2022. All patients were followed by the Hereditary Group of a single cancer center (Instituto do Cancer do Estado de Sao Paulo). Patients were included if they had a histopathological diagnosis of localized invasive carcinoma or in situ carcinoma of the breast. All patients met Revised Chompret criteria or Li Fraumeni like syndrome or family member of carrier TP53 or hereditary breast and ovarian Syndrome. Patients with only other types of breast cancer such as sarcoma and phyllodes tumor were excluded from the analysis.

You may qualify if:

• Breast cancer (histopathological diagnosis of localized invasive carcinoma or in situ carcinoma of the breast) and documented germline pathogenic variants of TP53.

You may not qualify if:

• Patients with only other types of breast cancer such as sarcoma and phyllodes tumor were excluded from the analysis.
• Metastatic Breast Cancer at diagnosis ("denovo")

Sponsors & Collaborators

• Instituto do Cancer do Estado de São Paulo: lead

Study Sites (1)

ICESP

São Paulo, 01.246-000, Brazil

Location

Biospecimen

Retention: SAMPLES WITH DNA

TP53 molecular analyses were initially based on the investigation of the p.R337H mutation by polymerase chain reaction/restriction fragment length polymorphism (PCR). In this method, PCR amplicons of exon 10 of the TP53 gene were digested by the Hha I restriction enzyme and then separated by agarose gel electrophoresis. This analysis can distinguish between different genotypes at the p.R337H mutation site, identifying homozygous, heterozygous and wild-type individuals for this specific mutation. Sanger sequencing of coding and splicing regions was performed in all negative cases to investigate other variants. Amplification products of exons 2-11 of TP53 Sequencing analyses were carried out on the 3130xl Genetic Analyzer. Classification of the variant pathogenicity was done according to the American College of Medical Genetics and Genomics guidelines, using VarSome or NGS germline panel. In the control group the analyses of germline painel where performed with NGS

MeSH Terms

Conditions

Breast Neoplasms; Li-Fraumeni Syndrome

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Vanessa Petry, MD

  Instituto do Cancer do Estado de São Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 19, 2021
• Study Start: December 2, 2018
• Primary Completion: August 7, 2021
• Study Completion: February 22, 2022
• Last Updated: August 9, 2022

Record last verified: 2022-08

Locations

BR (1)