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

Breast Cancer Clinical Trial

— BREAST-TP53  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04966923
• Other study ID #: 3.0840453
• Status: Completed
• Start date: December 2, 2018
• Est. completion date: February 22, 2022

Study information

• Verified date: August 2022
• Source: Instituto do Cancer do Estado de São Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 localized breast cancer diagnosed for each case included we will be selected 2 controls resulting in 90 control patients, for control 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: February 22, 2022
• Est. primary completion date: August 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

• Metastatic Breast Cancer at diagnosis ("denovo")

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Li-Fraumeni Syndrome

Intervention

Other:
• No intervention in this study
Analyses of pathogenic variant TP53 and variants in genetic test

Locations

Country	Name	City	State
Brazil	ICESP	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Instituto do Cancer do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)