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Phenotype and Prognosis of Patients With Breast Cancer and Pathogenic Variants of TP53 (BREAST TP53)

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ClinicalTrials.gov Identifier: NCT04966923
Recruitment Status : Recruiting
First Posted : July 19, 2021
Last Update Posted : July 19, 2021
Sponsor:
Information provided by (Responsible Party):
Instituto do Cancer do Estado de São Paulo

Tracking Information
First Submitted Date July 8, 2021
First Posted Date July 19, 2021
Last Update Posted Date July 19, 2021
Actual Study Start Date December 2, 2018
Estimated Primary Completion Date August 7, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 8, 2021)
Progression free survival [ Time Frame: 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) ]
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
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: July 8, 2021)
Overall Survival, causes of deaths [ Time Frame: 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) ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Phenotype and Prognosis of Patients With Breast Cancer and Pathogenic Variants of TP53
Official Title Phenotype and Prognosis of Patients With Breast Cancer and Pathogenic Variants of TP53 (BREAST TP53)
Brief Summary We did 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 2021. All patients were followed by the Hereditary Group of a single cancer center (Instituto do Cancer do Estado de Sao Paulo) and AC Camargo Cancer Center 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. Patients with only other types of breast cancer such as sarcoma and phyllodes tumor were excluded from the analysis.
Detailed Description

The primary outcome was progression free survival from specific breast cancer from patients with BC and TP53 mutation versus BC and no pathogenic variants documented in genetic test. 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), staging and immunohistochemistry subtype with no documented pathogenic variants in genetic test. With a sample of 135 patients with distribution 2:1, considering a two-tailed alpha of 5%, the study will have 80% power to identify a hazard hatio of 0.62 in the comparison of progression-free survival between the groups.

Descriptive statistics will be used to summarize clinical characteristics and treatments performed. Continuous variables may be compared between groups using T Student test or Mann-Whitney test, in the case of normal and non-normal data distribution, respectively. Categorical variables may be compared between groups using the Fisher exact test.

Progression-free survival will be estimated from the date of breast cancer diagnosis until the date of progression or date of recurrence (in cases of localized disease treated) of breast cancer. Death will not be considered as an event for progression-free survival, since patients with PV TP53 may have an increased risk of deaths from other neoplasms. The breast cancer specific survival will be estimated from the date of diagnosis of breast cancer until the date of death from the breast cancer. Patients without the specific events will be censored on the date of last follow-up.

The Kaplan-Meyer method will be used for survival estimates, comparing survival curves with log-rank testing. The Cox regression model will be used for hazard-ratio calculation and 95% confidence-interval. P value less than 0.05 will be considered statistically significant. Statistical analyses will be performed through Stata program, version 15.1 (StataCorp, Texas, USA).

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
The 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 were sequenced using the BigDye terminator v3.1 cycle sequencing kit, according to the manufacturer's instructions. 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.
Sampling Method Probability Sample
Study Population We did 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 2021. All patients were followed by the Hereditary Group of a single cancer center (Instituto do Cancer do Estado de Sao Paulo) and AC Camargo Cancer Center 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. Patients with only other types of breast cancer such as sarcoma and phyllodes tumor were excluded from the analysis.
Condition
  • Breast Cancer
  • TP53 R337H
  • Li-Fraumeni Syndrome
  • Prognosis Breast Cancer
Intervention Other: No intervention in this study
Analyses of pathogenic variant TP53 and variants in genetic test
Study Groups/Cohorts
  • Breast Cancer and documented pathogenic variant TP53
    Documented pathogenic or likely pathogenic variants of TP53 were identified using blood DNA colection and breast cancer diagnosis by histological confirmation. All patients met Revised Chompret criteria or Li Fraumeni like syndrome or family member of carrier TP53
    Intervention: Other: No intervention in this study
  • Breast Cancer and no documented pathogenic variants in genetic test
    Control with patients breast cancer and no pathogenic variants documented in a genetic test
    Intervention: Other: No intervention in this study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 8, 2021)
135
Original Estimated Enrollment Same as current
Estimated Study Completion Date February 5, 2023
Estimated Primary Completion Date August 7, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Patients with only other types of breast cancer such as sarcoma and phyllodes tumor were excluded from the analysis.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Listed Location Countries Brazil
Removed Location Countries  
 
Administrative Information
NCT Number NCT04966923
Other Study ID Numbers 3.0840453
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Instituto do Cancer do Estado de São Paulo
Study Sponsor Instituto do Cancer do Estado de São Paulo
Collaborators Not Provided
Investigators Not Provided
PRS Account Instituto do Cancer do Estado de São Paulo
Verification Date July 2021