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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • British Columbia
    • Abbotsford, British Columbia, Canada, V2S 0C2
      • Abbotsford Centre
    • Prince George, British Columbia, Canada, V2M 7E9
      • BC Cancer Agency, Centre for the North
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Centre
    • Victoria, British Columbia, Canada, V9R 6V5
      • BC Cancer Agency
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Cancer Centre
    • Kingston, Ontario, Canada
      • Cancer Centre of Southern Ontario at Kingston
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Centre
    • Oshawa, Ontario, Canada, L1G 2B9
      • R.S. McLaughlin Durham Regional Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Regional Cancer Centre
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Algoma District Cancer Program
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Niagara Health System
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Sciences
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1Z6
      • Princess Margaret Cancer Centre
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Centre integre de sante et de services sociaux de laval (CISSS de Laval)
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre Dame
    • Montreal, Quebec, Canada, H3T1E2
      • The Jewish General Hospital
    • Quebec city, Quebec, Canada, G1R 2J6
      • CHUQ - Pavillon Hotel-Dieu de Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CHUS - Hôpital Fleurimont
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • The Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This is a multicentre, single-arm prospective cohort study evaluating risk of IBTR following BCS in a group of women postulated to be at low risk for recurrence. Subjects will be followed for 10 years and will be assessed for recurrent disease, new primary cancer and survival. The primary outcome is IBTR

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Luminal A with other Clinical Criteria; BCS postulated to be at low risk for IBTR following Endocrine Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Overall survival (OS)	Overall survival (OS) defined as time from registration to death of any cause	5 years

Collaborators and Investigators

• Sponsor: Ontario Clinical Oncology Group (OCOG)
• Collaborators: British Columbia Cancer Agency
• Investigators: Principal Investigator: Tim Whelan, MD, Ontario Clinical Oncology Group (OCOG); Principal Investigator: Sally Smith, MD, British Columbia Cancer Agency (BCCA)

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): March 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 12, 2013
• First Submitted That Met QC Criteria: February 12, 2013
• First Posted (Estimated): February 15, 2013

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Luminal A; Ipsilateral Breast Tumour Recurrence
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Breast Neoplasms; Recurrence
• Other Study ID Numbers: OCOG-2012-LUMINA