A Prospective Cohort Study Evaluating Risk of Local Recurrence Following Breast Conserving Surgery and Endocrine Therapy in Low Risk Luminal A Breast Cancer

Breast Cancer Clinical Trial

— LUMINA  

Official title:

A Prospective Cohort Study Evaluating Risk of Local Recurrence Following Breast Conserving Surgery and Endocrine Therapy in Low Risk Luminal A Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01791829
• Other study ID #: OCOG-2012-LUMINA
• Status: Active, not recruiting
• Start date: July 2013
• Est. completion date: December 2024

Study information

• Verified date: August 2023
• Source: Ontario Clinical Oncology Group (OCOG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a multicentre, single-arm prospective cohort study evaluating risk of ipsilateral breast tumour recurrence(IBTR) following breast conserving surgery (BCS) in a group of women postulated to be at low risk for recurrence. Women with luminal A breast cancer determined by immunohistochemical(IHC) and other low risk clinical testing (see below) will be treated with endocrine therapy (tamoxifen or aromatase inhibitor) for five years and will not be treated with breast irradiation (BI). Subjects will be followed for 10 years and will be assessed for recurrent disease, new primary cancer and survival.

Description:

The independent prognostic ability of the luminal A subtype has been demonstrated in two retrospective analyses of prospective trials and suggests that luminal A combined with other known clinical prognostic factors could be used to select patients treated with BCS at very low risk for IBTR who could avoid BI. Given that using intrinsic subtyping combined with other clinical factors to identify women who could avoid BI would be a major change in clinical practice, we propose that a prospective study is necessary to confirm that such an approach can accurately identify a group of women at very low risk for IBTR following BCS.

We anticipate that the risk of IBTR in the low risk group is likely to be lower than that observed in previous trials (predicted to be < 5% at 5 years and < 10% at 10 years) for several reasons: first, our selection criteria (node negative, luminal A, > or = 55 years, tumours < or = 2cm, excision margin > or = 1mm post-BCS, absence of lobular cancers, extensive intraductal component and lymphovascular invasion) are more restrictive than in previous trials and second, the risks of IBTR are steadily decreasing over time due to improvements in mammographic screening, pre-op staging, tumour localization, and surgical practice. The expected low failure rates are unlikely to warrant the use of radiation.

A prospective cohort study was identified as the most appropriate and efficient design as our primary hypothesis is that a group of patients at very low risk of IBTR can be identified. A randomized trial could address the effectiveness of radiation in such a cohort of patients, but would require a much larger sample size to detect very small differences, which would not be clinically meaningful. During the conduct of this trial it is anticipated that patients who do not meet study criteria or who decline study enrollment, will continue to receive BI after BCS.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 2024
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

1. Female patient > or = 55 years of age with a new diagnosis of invasive carcinoma of the breast (ductal, tubular or mucinous only) with primary tumour < or =2cm on microscopic exam, with no evidence of metastatic disease;

2. ER positive (> or =1%) and PR positive (>20%) and HER2 negative (Immunohistochemical (IHC) or In Situ Hybridization (ISH) approach);

3. Treated by BCS with microscopically clear resection margins > or = 1mm for invasive and non-invasive disease or no residual disease on re-excision;

4. Negative axillary node involvement determined by sentinel node biopsy or axillary node dissection.

Exclusion Criteria:

1. Clinical or pathological evidence of T4 disease (i.e. extension to chest wall, skin involvement, peau d'orange, or inflammatory breast cancer).

2. Multifocal or multicentric disease.

3. Evidence of an extensive intraductal component (defined as a tumour that is composed of 25% or more of DCIS and the DCIS extends beyond the gross dimensions of the tumour), or disease limited to micro invasion only.

4. Grade 3 histology for invasive disease

5. Evidence of lymphovascular invasion.

6. Evidence of disease on pre-operative mammogram, aside from primary cancer treated by breast conserving surgery.

7. Bilateral malignancy of the breast (synchronous or metachronous).

8. Known BRCA 1 or 2 mutations.

9. History of non-breast cancer malignancies if not disease free for > 5 years and considered low risk of recurrence with the exception of treated carcinoma in-situ of the cervix, endometrium or colon, melanoma in-situ and basal or squamous cell carcinoma of the skin.

10. Serious non-malignant disease associated with a life expectancy < 10 years.

11. Inability to be treated with or to tolerate endocrine therapy.

12. Psychiatric or addictive disorder, which would preclude obtaining informed consent or adherence to protocol.

13. Geographic inaccessibility for follow-up.

14. Inability to understand or unable to provide written informed consent.

15. Inability to be registered on study within 12 weeks of the last surgical procedure on the breast.

16. Central testing for Ki67 > 13.25% consistent with the luminal B subtype

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Recurrence

Locations

Country	Name	City	State
Canada	Abbotsford Centre	Abbotsford	British Columbia
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Cancer Centre of Southern Ontario at Kingston	Kingston	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	Centre integre de sante et de services sociaux de laval (CISSS de Laval)	Laval	Quebec
Canada	London Regional Cancer Centre	London	Ontario
Canada	CHUM - Hopital Notre Dame	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	The Jewish General Hospital	Montreal	Quebec
Canada	R.S. McLaughlin Durham Regional Cancer Centre	Oshawa	Ontario
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	BC Cancer Agency, Centre for the North	Prince George	British Columbia
Canada	CHUQ - Pavillon Hotel-Dieu de Quebec	Quebec city	Quebec
Canada	The Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program	Sault Ste. Marie	Ontario
Canada	CHUS - Hopital Fleurimont	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Northeastern Ontario Regional Cancer Centre	Sudbury	Ontario
Canada	Thunder Bay Regional Health Sciences	Thunder Bay	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	BCCA - Vancouver Centre	Vancouver	British Columbia
Canada	BC Cancer Agency	Victoria	British Columbia
Canada	Cancer Care Manitoba	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Ontario Clinical Oncology Group (OCOG)	British Columbia Cancer Agency

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ipsilateral Breast Tumour Recurrence (IBTR)	The primary outcome is IBTR defined as recurrent invasive or in-situ cancer in the ipsilateral breast during follow-up. Histological evidence of recurrence will be required. All recurrences will be reviewed by a central adjudication committee.	5 years
Secondary	Recurrence Free interval (RFI)	Recurrence free interval (RFI) defined as time from registration to time of documented recurrent disease (ipsilateral breast, regional or distant)	5 years
Secondary	Event-free survival (EFS)	Event-free survival (EFS) defined as the time from registration to the time of documented IBTR, regional (ipsilateral axilla, supraclavicular or internal mammary nodes), distant recurrence (bone, liver, lung, brain, etc.), contralateral breast cancer, new primary cancer or death	5 years
Secondary	Overall survival (OS)	Overall survival (OS) defined as time from registration to death of any cause	5 years

External Links

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