Next-Generation Sequencing-based Germline and Somatic Genetic Testing in Triple-negative Breast Cancer (PERSONA)

Evaluating the Feasibility of Next-Generation Sequencing - Based Germline and Somatic Genetic Testing in Triple-negative Breast Cancer. The PERSONA-breast Trial

For patients with triple negative breast cancer, implementation of genetic testing in decision making might impact both risk management for the patient and her family, but also, importantly, therapeutic management.

Identifying genetically predisposed subjects dictates risk-reducing strategies that may imply bilateral salpingo-oophorectomy and mastectomy or long term medical approaches. In the advanced setting, genetic testing can influence decision for medical therapy (e.g. use of platinum derivatives, poly-ADP ribose polymerase inhibitors (PARP inhibitors) in breast cancer patients with breast cancer susceptibility gene (BRCA) mutation.

The selection of patients for testing has long relied on the presence of a strong family history of breast and ovarian cancer. It is now clear that this criterion will result in substantial numbers of those with a BRCA mutation being missed.

Systematic large-scale genetic testing, simultaneously on germline and somatic tissues, is likely to improve decisional algorithms in patients with ovarian cancer. Feasibility of such approach in the clinical setting, in terms of a turnaround time compatible with clinical needs and sensitivity comparable if not superior to single-gene testing needs to be demonstrated before such diagnostic platforms can be routinely implemented in the diagnostic workflow. This is the scope of the present study.

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer

Detailed Description

Systematic large-scale genetic testing, simultaneously on germline and somatic tissues, is likely to improve decisional algorithms in patients with triple negative breast cancers.

Feasibility of such approach in the clinical setting, in terms of a turnaround time compatible with clinical needs and sensitivity comparable if not superior to single-gene testing needs to be demonstrated before such diagnostc platforms can be routinely implemented in the diagnostic workflow.

Two platforms will be used during the course of the study. The Illumina TruSight Cancer Risk panel is a commercially validated targeted enrichment panel which targets 94 genes and 284 SNPs (Single Nucleotide Polymorphism) associated with a predisposition towards cancer.

The GermSom panel was developed at European Institute of Oncology (IEO) in collaboration with institutions within the Alleanza Contro il Cancro consortium and manufactured by Agilent Technologies. It includes 349 genes with an established function in the biology and/or pharmacological actionability of multiple solid tumors, including breast cancer. It includes all the genomic regions analysed in the Illumina Trusight panel, plus 32 additional regions associated with risk of multiple tumors.

Patients will receive detailed genetic characterization of their germline and their tumor. This will provide the best possible characterization of their risk of developing of a secondary malignancy and can be exploited to identify families at risk for hereditary cancer risk. Patients will also benefit from an increased likelihood of being treated with appropriate drugs and of receiving appropriate surgery.

• Study Type: Observational
• Enrollment (Estimated): 264

Contacts and Locations

• Study Contact: Name: Viviana E Galimberti, MD; Phone Number: +390257489717; Email: viviana.galimberti@ieo.it

Study Locations

• Italy
  • Milan, Italy
    • Recruiting
    • Istituto Europeo di Oncologia
    • Contact: Viviana E Galimberti, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with triple-negative breast cancer, stage I-III, cadidates for surgery

Description

Inclusion Criteria:

1. age between 18 and 60 years
2. has signed informed consent
3. histologically confirmed triple negative breast cancer (ER (Estrogen Receptors) < 1%, PgR (Progesterone Receptors) < 1%, HER2/neu negative (IHC 0, 1+ or 2+ FISH negative).
4. Stage I-III
5. Able to undergo surgery (primary or post-neoadjuvant)
6. Availability of surgical/bioptic material within 6 months from enrolment

Exclusion Criteria:

• unable or unwilling to receive genetic counselling

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of mutations in breast cancer risk-associated genes	Evaluate the prevalence of clinically relevant mutations in breast cancer risk-associated genes	3 months
Genetic test turnaround time	Evaluate feasibility of genetic testing for clinical decision making	6 months
Percentage of informative specimens	Percentage of patients with positive germline testing for target genes	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of all other mutations	Incidence of all other mutations	3 months
disease-free survival	collection of disease associated events during follow-up	10 years
overall survival	collection of death events during follow-up	10 years

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Principal Investigator: Viviana E Galimberti, MD, IEO

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; genetic testing
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: IEO 0761/

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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