Oncotype DX in BRCA-mutated Breast Cancer Patients: Our Experience. A Retrospective Observational Monocentric Study (OnBRA)

The study aims to evaluate the distribution of the Oncotype DX RS® genomic test in patients with ER-positive and HER2-negative breast cancer treated from January 2012 to December 2021, focusing on patients presenting germline mutations.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Genetic Predisposition
• Intervention / Treatment: Genetic: Oncotype DX assay

Detailed Description

In the past decades, genetic testing for cancer susceptibility has become essential in breast cancer (BC) management. Up to 10% of BC cases are associated with an inherited mutation in various genes, especially BRCA 1 and BRCA 2. Estrogen receptor (ER) positivity is observed in 22% on BRCA 1 and 77% of BRCA 2 mutation carrier; moreover, other genes are strongly related to ER-positive cancer.

Oncotype DX assay (Genomic Health, Inc, Redwood City, Calif) is a 21 gene panel developed to predict the risk of tumor recurrence in patients with ER-positive and human epidermal growth factor 2 (HER2)- negative BC; nowadays, this test represents a standard of care to guide adjuvant chemotherapy decision recommended in several guidelines. According to Oncotype DX Recurrent Score (RS)® a high RS shows a worse prognosis and predicts chemotherapy benefit in patients with ER-positive HER2-negative BC.

Combining Oncotype DX RS® with other risk factor elements, in particular germline mutations, could help to select patients who would benefit from an appropriate adjuvant therapy.

This retrospective observational study aims to evaluate Oncotype DX RS® distribution in ER-positive HER2-negative BC patients treated from January 2012 to December 2021, focusing on patients harboring mutation in BC-associated genes compared to the general population.

• Study Type: Observational
• Enrollment (Actual): 250

Contacts and Locations

Study Locations

• Italy
  • MI
    • Milan, MI, Italy, 20132
      • Irccs Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Breast cancer patients who underwent surgery as primary treatment and eligible for Oncotype DX assay.

Description

Inclusion Criteria:

• Age at diagnosis at least 18 years
• Women who underwent breast surgery in OSR
• Patients with ER-positive, HER2-unamplified early-stage BC who underwent the Oncotype DX assay, according to the standard of care.

Exclusion Criteria:

• Male
• ER negative or HER2 amplified disease
• Patient s who did not undergo breast surgery in OSR
• Patient s who did not undergo the Oncotype Dx assay

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Wild type patients; Patients with no mutations or VUS in Breast Cancer-related genes candidated to surgery as primary treatment and eligible for Oncotype DX assay.	Genetic: Oncotype DX assay; Oncotype DX assay (Genomic Health, Inc, Redwood City, Calif) is a 21 gene panel developed to predict the risk of tumor recurrence in patients with ER-positive and human epidermal growth factor 2 (HER2)- negative breast cancer (BC); nowadays, this test represents a standard of care to guide adjuvant chemotherapy decision recommended in several guidelines. According to Oncotype DX Recurrent Score (RS)® a high RS shows a worse prognosis and predicts chemotherapy benefit in patients with ER-positive HER2-negative BC.
VUS patients; Patients with VUS in Breast Cancer-related genes candidated to surgery as primary treatment and eligible for Oncotype DX assay.	Genetic: Oncotype DX assay; Oncotype DX assay (Genomic Health, Inc, Redwood City, Calif) is a 21 gene panel developed to predict the risk of tumor recurrence in patients with ER-positive and human epidermal growth factor 2 (HER2)- negative breast cancer (BC); nowadays, this test represents a standard of care to guide adjuvant chemotherapy decision recommended in several guidelines. According to Oncotype DX Recurrent Score (RS)® a high RS shows a worse prognosis and predicts chemotherapy benefit in patients with ER-positive HER2-negative BC.
Mutated patients; Patients with mutation in Breast Cancer-related genes candidated to surgery as primary treatment and eligible for Oncotype DX assay.	Genetic: Oncotype DX assay; Oncotype DX assay (Genomic Health, Inc, Redwood City, Calif) is a 21 gene panel developed to predict the risk of tumor recurrence in patients with ER-positive and human epidermal growth factor 2 (HER2)- negative breast cancer (BC); nowadays, this test represents a standard of care to guide adjuvant chemotherapy decision recommended in several guidelines. According to Oncotype DX Recurrent Score (RS)® a high RS shows a worse prognosis and predicts chemotherapy benefit in patients with ER-positive HER2-negative BC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oncotype DX assay and RS® in participants.	To evaluate the Oncotype DX RS® distribution in ER-positive early BC patients comparing patients with a deleterious germline mutation, patients with a VUS in BC-related genes and patients with no mutation.	30 days after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oncotype DX assay and RS® in participants by menopausal or nodal status.	To evaluate Oncotype DX RS® distribution stratifying patients by menopausal or nodal status.	30 days after surgery
Distant or local recurrence.	Evaluation of distant or local recurrence from follow-up data	Up to 10 years after surgery

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Investigators: Study Director: Oreste Davide Gentilini, Vita-Salute San Raffaele University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: BRCA2; BRCA1; Genomic test
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Disease Susceptibility; Breast Neoplasms; Genetic Predisposition to Disease
• Other Study ID Numbers: CET 175-2024

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