The Impact of the Gene Recurrence Score on Chemotherapy Prescribing in ER Positive, Lymph Node Positive Early Stage Breast Cancer

• ClinicalTrials.gov Identifier: NCT03843346
• Recruitment Status: Active, not recruiting
• First Posted: February 18, 2019
• Last Update Posted: January 18, 2022
• Sponsor: Cancer Trials Ireland
• Information provided by (Responsible Party): Cancer Trials Ireland

Study Description

Brief Summary:

This study examines the impact of an additional tumour test called the 21 gene Recurrence Score (OncotypeDx®), a commercially available test on a Medical Oncologist's decision to recommend chemotherapy.

Condition or disease
Breast Cancer

Detailed Description:

After a breast cancer and any lymph glands have been surgically removed, further (adjuvant) treatment is generally given to reduce the risk of cancer recurrence. For patients with estrogen receptor (ER) positive breast cancer, this treatment has traditionally been chemotherapy and hormone therapy. However, it is increasingly recognised that tumours which are ER positive and negative for the human epidermal growth factor receptor 2 (HER2), are relatively resistant to chemotherapy. It is likely that many more people are exposed to the risks for chemotherapy than ever benefit from it. In order to select patients who will get more benefit from chemotherapy and to spare those who get very little benefit from side effects, risk assessment tools are being developed.

The 21 Gene Recurrence Score is a test that examines the tumour genes to estimate the risk of the tumour relapsing and possible chemotherapy benefits. Currently, the 21 Gene Recurrence Score (OncotypeDx®) is used In Ireland for patients with no cancer in their lymph nodes. For these patients it can help in deciding who should get chemotherapy. Patients with low scores can sometimes avoid chemotherapy. In some countries, this test is offered to almost all patients with ER positive breast cancer, irrespective of whether the cancer has spread to lymph nodes or not. However, in Ireland this test is not standardly available for patients who have breast cancer involving lymph nodes.

Study Design

• Study Type: Observational
• Actual Enrollment: 87 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: The Impact of the 21 Gene Recurrence Score (RS) on Chemotherapy Prescribing in Estrogen Receptor Positive, Lymph Node Positive Early Stage Breast Cancer in Ireland
• Actual Study Start Date: March 16, 2017
• Actual Primary Completion Date: December 10, 2021
• Estimated Study Completion Date: February 2022

Groups and Cohorts

Group/Cohort
Cohort 1: Postoperative group; Consists of 75 patients who have completed definite surgery for their primary breast cancer as determined by a Consultant Surgeon and have been referred to a Medical Oncologist for consideration of adjuvant chemotherapy.; Tumours of any size will be eligible; Between 1 and 3 lymph nodes involved by tumour as assessed by Consultant Pathologist; Micro metastases (<=0.2mm) will be eligibile; Isolated tumour cells only (node negative i+/i-) are excluded
Cohort 2: Preoperative group; Consists of 75 patients who have been referred by a Consultant Surgeon to a Medical Oncologist for consideration of neoadjuvant (preoperative) chemotherapy.; Min tumour size 2.1mm (T2); Histological proof of involvement of at 1 lymph node, including micrometastases (<=0.2mm)

Outcome Measures

Primary Outcome Measures :

1. Recommended Chemotherapy [ Time Frame: 3 years ]
   The percentage reduction in the number of patients for whom chemotherapy is recommended following resection of their primary breast cancer and testing with the 21 gene RS (cohort 1; n=75)

Secondary Outcome Measures :

1. Impact of gene RS [ Time Frame: 3 years ]
   Examine the impact of the 21 gene RS on chemotherapy recommendations in operable breast cancer in the postoperative and preoperative setting (cohorts 1 and 2; n=150) using questionnaires completed by Medical Oncologists.
2. Complete Response [ Time Frame: 3 years ]
   Investigate the correlation between the 21 gene RS and pathological complete response from preoperative therapy in operable breast cancer (cohort 2; n=75).
3. Radiological Response Rate [ Time Frame: 3 years ]
   Determine whether the 21 gene RS correlates with clinical, radiological response rate and the MD Anderson residual cancer burden score following preoperative therapy (cohort 2; n=75).
4. Economic Impact [ Time Frame: 3 years ]
   Determine the economic impact of the 21 gene RS testing on ER positive, node positive breast cancer patients (cohorts 1 and 2; n=150) using a simple budget impact model

Biospecimen Retention:   Samples With DNA

Tissue will be sent for 21 gene RS (OncotypeDx(r)) testing to Genomic Health as per standard clinical practice for patients with node negative tumours.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The study will examine 2 cohorts of patients;

• 75 patients (cohort 1; "postoperative") who have undergone resection of their primary breast cancer and
• 75 patients (cohort 2; "preoperative") who are referred to a Medical Oncologist for consideration of neoadjuvant (preoperative) treatment.

Both cohorts will have ER positive, lymph node positive breast cancer and both cohorts will undergo testing with the 21 gene RS.

Criteria

Inclusion Criteria:

General Inclusion Criteria (All Patients)

1. Age 18 years of age or older
2. ER Positive Tumours (≥1% positive cells or Allred score ≥ 2 (Appendix 1))
3. Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer (0-1 by IHC or FISH <2.0)
4. No evidence of metastatic disease on CT, bone scan or other imaging
5. Fit for consideration of chemotherapy as determined by the Investigator
6. Adequate performance status (Eastern Cooperative Oncology Group (ECOG) 0 or 1 (Appendix 2))

Inclusion Criteria - Cohort 1 (Postoperative Patients): N= 75

1. Adequate surgical excision of breast tumour (mastectomy or lumpectomy) and lymph nodes (sentinel lymph biopsy or axillary dissection)
2. Any tumour size (T stage (Appendix 3))
3. Involvement of 1-3 lymph nodes (N1, including micrometastases)

Inclusion Criteria - Cohort 2 (Preoperative Patients): N= 75

1. Candidates for preoperative therapy for early breast cancer
2. T2-T4 tumours
3. Involvement of at least one lymph node, (including micrometastases) on biopsy
4. Adequate tissue from core biopsy for 21 gene RS testing (approximate minimum 5mm)

Exclusion Criteria (All patients):

1. ER negative tumour (Allred score 0-1)
2. HER2 positive tumours as defined by IHC 3+ or FISH ≥ 2.0
3. Node negative disease, including those with Isolated tumour cells only (node negative i+/i-)
4. Known metastatic breast cancer
5. Performance status ≥ 2
6. Patients not considered by their treating physician to be fit to undergo chemotherapy.
7. Men with breast cancer.

Contacts and Locations

Locations

Ireland

Letterkenny University Hospital

Letterkenny, Co. Donegal, Ireland

St Vincent's University Hospital

Dublin, Dublin 4, Ireland

Mater Misericordiae University Hospital & Mater Private Hospital

Dublin, Dublin 7, Ireland

Beaumont Hospital

Dublin, Dublin 9, Ireland

Bon Secour Cork

Cork, Ireland

Cork University Hospital

Cork, Ireland

St James' Hospital

Dublin, Ireland

University Hospital Galway

Galway, Ireland

University Hospital Limerick

Limerick, Ireland, V94 F858

University Hospital Waterford

Waterford, Ireland

Sponsors and Collaborators

Cancer Trials Ireland

Investigators

• Principal Investigator: Dr Patrick Morris; Beaumont Hospital

More Information

• Responsible Party: Cancer Trials Ireland
• ClinicalTrials.gov Identifier: NCT03843346
• Other Study ID Numbers: CTRIAL-IE 15-34
• First Posted: February 18, 2019
• Last Update Posted: January 18, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Breast Neoplasms; Recurrence; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Disease Attributes; Pathologic Processes