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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Li-Fraumeni Syndrome; TP53 R337H; Prognosis Breast Cancer
• Intervention / Treatment: Other: No intervention in this study

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 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).

• Study Type: Observational
• Enrollment (Actual): 135

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01.246-000
    • ICESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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")

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Analyses of pathogenic variant TP53 and variants in genetic test
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; Analyses of pathogenic variant TP53 and variants in genetic test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Investigators: Principal Investigator: Vanessa Petry, MD, Instituto do Cancer do Estado de Sao Paulo

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 2, 2018
• Primary Completion (ACTUAL): August 7, 2021
• Study Completion (ACTUAL): February 22, 2022

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (ACTUAL): July 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 5, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; TP53
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Genetic Diseases, Inborn; Neoplastic Syndromes, Hereditary; DNA Repair-Deficiency Disorders; Breast Neoplasms; Li-Fraumeni Syndrome
• Other Study ID Numbers: 3.0840453

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No