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

Sponsor

Ontario Clinical Oncology Group (OCOG) (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01791829

Collaborator

British Columbia Cancer Agency (Other)

500

Enrollment

Locations

120

Duration (Months)

18.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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 Design

Study Type:

Observational

Actual Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Study Start Date :

Jul 1, 2013

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Luminal A with other Clinical Criteria BCS postulated to be at low risk for IBTR following Endocrine Therapy

Outcome Measures

Primary Outcome Measures

Ipsilateral Breast Tumour Recurrence (IBTR) [5 years]
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.

Secondary Outcome Measures

Recurrence Free interval (RFI) [5 years]
Recurrence free interval (RFI) defined as time from registration to time of documented recurrent disease (ipsilateral breast, regional or distant)
Event-free survival (EFS) [5 years]
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
Overall survival (OS) [5 years]
Overall survival (OS) defined as time from registration to death of any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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;
ER positive (> or =1%) and PR positive (>20%) and HER2 negative (Immunohistochemical (IHC) or In Situ Hybridization (ISH) approach);
Treated by BCS with microscopically clear resection margins > or = 1mm for invasive and non-invasive disease or no residual disease on re-excision;
Negative axillary node involvement determined by sentinel node biopsy or axillary node dissection.

Exclusion Criteria:

Clinical or pathological evidence of T4 disease (i.e. extension to chest wall, skin involvement, peau d'orange, or inflammatory breast cancer).
Multifocal or multicentric disease.
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.
Grade 3 histology for invasive disease
Evidence of lymphovascular invasion.
Evidence of disease on pre-operative mammogram, aside from primary cancer treated by breast conserving surgery.
Bilateral malignancy of the breast (synchronous or metachronous).
Known BRCA 1 or 2 mutations.
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.
Serious non-malignant disease associated with a life expectancy < 10 years.
Inability to be treated with or to tolerate endocrine therapy.
Psychiatric or addictive disorder, which would preclude obtaining informed consent or adherence to protocol.
Geographic inaccessibility for follow-up.
Inability to understand or unable to provide written informed consent.
Inability to be registered on study within 12 weeks of the last surgical procedure on the breast.
Central testing for Ki67 > 13.25% consistent with the luminal B subtype

Contacts and Locations

Locations

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