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

Recruiting

• Conditions: Triple Negative Breast Cancer

• Registration Number: NCT03920488
• Lead Sponsor: European Institute of Oncology

Brief Summary

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.

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 Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2019-04-16
• Study First Submitted QC: 2019-04-16
• Study First Posted: 2019-04-19
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-27
• Last Update Posted: 2023-06-28
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 264

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of all other mutations	3 months	Incidence of all other mutations
disease-free survival	10 years	collection of disease associated events during follow-up
overall survival	10 years	collection of death events during follow-up

Trial Locations

Locations (1)

Istituto Europeo di Oncologia; 🇮🇹 Milan, Italy