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

NCT ID: NCT01791829

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2027-07-31

Brief 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.

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.

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Luminal A with other Clinical Criteria

BCS postulated to be at low risk for IBTR following Endocrine Therapy

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

British Columbia Cancer Agency

OTHER

Sponsor Role: collaborator

Ontario Clinical Oncology Group (OCOG)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Whelan, MD

Role: PRINCIPAL_INVESTIGATOR

Ontario Clinical Oncology Group (OCOG)

Sally Smith, MD

Role: PRINCIPAL_INVESTIGATOR

British Columbia Cancer Agency (BCCA)

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Abbotsford Centre

Abbotsford, British Columbia, Canada

BC Cancer Agency, Centre for the North

Prince George, British Columbia, Canada

BCCA - Vancouver Centre

Vancouver, British Columbia, Canada

BC Cancer Agency

Victoria, British Columbia, Canada

Cancer Care Manitoba

Winnipeg, Manitoba, Canada

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

Northeastern Ontario Regional Cancer Centre

Greater Sudbury, Ontario, 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

London Regional Cancer Centre

London, Ontario, Canada

R.S. McLaughlin Durham Regional Cancer Centre

Oshawa, Ontario, Canada

Ottawa Regional Cancer Centre

Ottawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Thunder Bay Regional Health Sciences

Thunder Bay, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Centre integre de sante et de services sociaux de laval (CISSS de Laval)

Laval, Quebec, Canada

CHUM - Hopital Notre Dame

Montreal, Quebec, Canada

The Jewish General Hospital

Montreal, Quebec, Canada

McGill University Health Centre

Montreal, Quebec, Canada

CHUQ - Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

CHUS - Hopital Fleurimont

Sherbrooke, Quebec, Canada

The Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

Nielsen TO, Leung SCY, Riaz N, Mulligan AM, Kos Z, Bane A, Whelan TJ. Ki67 assessment protocol as an integral biomarker for avoiding radiotherapy in the LUMINA breast cancer trial. Histopathology. 2023 Dec;83(6):903-911. doi: 10.1111/his.15032. Epub 2023 Aug 23.

Reference Type: DERIVED

PMID: 37609778 (View on PubMed)

Whelan TJ, Smith S, Parpia S, Fyles AW, Bane A, Liu FF, Rakovitch E, Chang L, Stevens C, Bowen J, Provencher S, Theberge V, Mulligan AM, Kos Z, Akra MA, Voduc KD, Hijal T, Dayes IS, Pond G, Wright JR, Nielsen TO, Levine MN; LUMINA Study Investigators. Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer. N Engl J Med. 2023 Aug 17;389(7):612-619. doi: 10.1056/NEJMoa2302344.

Reference Type: DERIVED

PMID: 37585627 (View on PubMed)

Related Links

http://www.ocog.ca

Related Info

Other Identifiers

OCOG-2012-LUMINA

Identifier Type: -

Identifier Source: org_study_id