Ignite Creation Date:
2024-05-11 @ 8:30 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06403904
Status:
RECRUITING
Last Update Posted:
2024-05-08
First Post:
2023-12-22
Brief Title:
Assessing Clinical Features and Outcome of Breast Cancer in PALB2 Mutation Carriers the Palbreast Study
Sponsor:
Azienda Ospedaliero-Universitaria di Modena
Organization:
Azienda Ospedaliero-Universitaria di Modena
Study Overview
Official Title:
Assessing Clinical Features and Outcome of Breast Cancer in PALB2
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PALBREAST
Brief Summary:
The Modena hereditary breast cancer group identified 3498 BRCA test candidates affected by breast cancer BC Among those 392 were BRCA12 positive 112 Since 2018 the site started to analyze eligible BC patients by multi gene panel MGP test Fifty hundred sixty BRCA negative patients have been recalled whereas other 934 were firstly analyzed by MGP Totally among 1494 BC patients analyzed by MGP test 33 were PALB2 mutation carriers 2 By involving the Italian Society of Genetic Oncology and 11 European Institutions it is calculated to identify about 300 PALB2 mutation carriers
PALB2 is a breast cancer susceptibility gene that encodes the BRCA2- interacting protein Mono-allelic mutations of PALB2 are associated with an increased risk for breast and ovarian cancer in women prostate cancer in men and pancreatic cancer in both gender Women with no family history of breast cancer have a cumulative risk of 33 compared to 58 in women with two or more family members with breast cancer Several studies with populations ranging from to 54 to 362 individuals aimed to describe breast cancer phenotypic characteristics in PALB2 mutation carriers Some of these studies suggested an association with triple-negative phenotype older age at diagnosis 30 years tumor size 2 cm negative HER2 status lymph nodes positive and bilaterality Nevertheless results among different studies are contradictory and no data on prognosis of these patients are reported Furthermore the clinical potential of PARP inhibition beyond currently approved indications to additional patients whose tumors have epigenetic changes affecting homologous recombination repair raises new interest in PALB2 mutations as molecular target
Primary objectives is to study the incidence and mortality rates of gPALB2 Breast Cancer
PALB2 is a breast cancer susceptibility gene that encodes the BRCA2- interacting protein Mono-allelic mutations of PALB2 are associated with an increased risk for breast and ovarian cancer in women prostate cancer in men and pancreatic cancer in both gender Women with no family history of breast cancer have a cumulative risk of 33 compared to 58 in women with two or more family members with breast cancer Several studies with populations ranging from to 54 to 362 individuals aimed to describe breast cancer phenotypic characteristics in PALB2 mutation carriers Some of these studies suggested an association with triple-negative phenotype older age at diagnosis 30 years tumor size 2 cm negative HER2 status lymph nodes positive and bilaterality Nevertheless results among different studies are contradictory and no data on prognosis of these patients are reported Furthermore the clinical potential of PARP inhibition beyond currently approved indications to additional patients whose tumors have epigenetic changes affecting homologous recombination repair raises new interest in PALB2 mutations as molecular target
Primary objectives is to study the incidence and mortality rates of gPALB2 Breast Cancer
Detailed Description:
This is a multicenter hospital-based retrospective cohort control study conducted across several Institutions with known expertise in managing hereditary breast cancer
It is planned to enrol at least 300 PALB2-related BC diagnosed at the different Units and 300 BC as control group tested for multigene panel and resulted negative for mutations It is expected to complete the accrual in one year furthermore a minimum follow-up of one more year is required for the final analysis of primary and secondary endpoints
Since some delay in the Ethical committee approvals at different Centers can rising the study could be extended for another year Subjects will be inserted in the registry after having identified a pathogenic or likely pathogenic germline PALB2 mutation All BC stages at the diagnosis will be included in the analysis The BC mutation negative control group will be consecutively selected from each center as ratio 11 in respect with the number of gPALB2 mutated patients enrolled matching those for age stage and period of diagnosis The following data for each patient will be collected
Demographic and clinical characteristics age at diagnosis BMI
Tumor characteristics breast imaging US mammogram breast MRI cito-histological examination from FNAcore biopsy multifocality or bilaterality clinical stage at diagnosis
Data about surgery and pathological features date of surgery the date of the primary tumor removal type of surgery tumor size and number of positive lymph nodes pTN biological features on surgical sample histological type ER PR HER2 Ki-67 grade TILs AR
Systemic treatment modalities neoadjuvant adjuvant advanced therapies with a detailed description of the treatment regimens drugs administered dosage of drugs and duration with start and end dates In patients that underwent neoadjuvant treatment data about pathological response ypTN and local regional treatment after NAC were collected pCR is defined as documented CR to NAC andor ypT0is N0
Type of radiotherapy performed and duration
Type of first relapse localdistant location of lesions date of detection and therapie
Data concerning family history and other primary tumours
Outcomes in terms of OS and DFS
Patients participation in previous studies Patients characteristics and the distribution of each parameter across will be reported as absolute and percentage frequencies For each group of patients registered at different Centers the number of all tests performed will be reported as denominator in order to establish the frequencies of mutations in all the European countries
Outcomes of interest will be DFS DDFS and OS in the cohort and control groups DFS DDFS and OS curves will be conducted using Kaplan-Meier method and time time-to-event distributions will be compared with log-rank test univariate regression Log-rank test will be used to compare the difference between values over and under the selected cut-off on survival curves Multivariate analysis will be conducted using Cox proportional hazard models to identify significant predictors of mortality In case of documented PD each participant will be contacted by telephone every 12 weeks -14 days to assess for survival status until withdrawal of consent to participate in the study becoming lost to follow up death or end of the study whichever occurs first Statistical analysis will be conducted using SPSS Statistics for Windows Version 230 IBM Corporation Armonk NY USA
In order to minimise bias on the subjects selection the analysts will not be informed about the origin of the patients being the number attributed to each centre blinded for the cohort and control group
For details on what is included in the efficacy and safety endpoints see Section 3 Objectives and Endpoints
It is planned to enrol at least 300 PALB2-related BC diagnosed at the different Units and 300 BC as control group tested for multigene panel and resulted negative for mutations It is expected to complete the accrual in one year furthermore a minimum follow-up of one more year is required for the final analysis of primary and secondary endpoints
Since some delay in the Ethical committee approvals at different Centers can rising the study could be extended for another year Subjects will be inserted in the registry after having identified a pathogenic or likely pathogenic germline PALB2 mutation All BC stages at the diagnosis will be included in the analysis The BC mutation negative control group will be consecutively selected from each center as ratio 11 in respect with the number of gPALB2 mutated patients enrolled matching those for age stage and period of diagnosis The following data for each patient will be collected
Demographic and clinical characteristics age at diagnosis BMI
Tumor characteristics breast imaging US mammogram breast MRI cito-histological examination from FNAcore biopsy multifocality or bilaterality clinical stage at diagnosis
Data about surgery and pathological features date of surgery the date of the primary tumor removal type of surgery tumor size and number of positive lymph nodes pTN biological features on surgical sample histological type ER PR HER2 Ki-67 grade TILs AR
Systemic treatment modalities neoadjuvant adjuvant advanced therapies with a detailed description of the treatment regimens drugs administered dosage of drugs and duration with start and end dates In patients that underwent neoadjuvant treatment data about pathological response ypTN and local regional treatment after NAC were collected pCR is defined as documented CR to NAC andor ypT0is N0
Type of radiotherapy performed and duration
Type of first relapse localdistant location of lesions date of detection and therapie
Data concerning family history and other primary tumours
Outcomes in terms of OS and DFS
Patients participation in previous studies Patients characteristics and the distribution of each parameter across will be reported as absolute and percentage frequencies For each group of patients registered at different Centers the number of all tests performed will be reported as denominator in order to establish the frequencies of mutations in all the European countries
Outcomes of interest will be DFS DDFS and OS in the cohort and control groups DFS DDFS and OS curves will be conducted using Kaplan-Meier method and time time-to-event distributions will be compared with log-rank test univariate regression Log-rank test will be used to compare the difference between values over and under the selected cut-off on survival curves Multivariate analysis will be conducted using Cox proportional hazard models to identify significant predictors of mortality In case of documented PD each participant will be contacted by telephone every 12 weeks -14 days to assess for survival status until withdrawal of consent to participate in the study becoming lost to follow up death or end of the study whichever occurs first Statistical analysis will be conducted using SPSS Statistics for Windows Version 230 IBM Corporation Armonk NY USA
In order to minimise bias on the subjects selection the analysts will not be informed about the origin of the patients being the number attributed to each centre blinded for the cohort and control group
For details on what is included in the efficacy and safety endpoints see Section 3 Objectives and Endpoints
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None