Clinical trial NCT01791829: A Prospective Cohort Study Evaluating Risk of Local Recurrence Following Breast Conserving Surgery and Endocrine Therapy in Low Risk Luminal A Breast Cancer
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 type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Breast Cancer
Keywords: Luminal A
Ipsilateral Breast Tumour Recurrence
Lead sponsor: Ontario Clinical Oncology Group (OCOG)
Sponsor class: OTHER
Collaborators: name: British Columbia Cancer Agency
First posted: 2013-02-15
Enrollment: 500
Sex: FEMALE
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Ipsilateral Breast Tumour Recurrence (IBTR)
timeFrame: 5 years
Secondary outcomes:
measure: Recurrence Free interval (RFI)
timeFrame: 5 years
measure: Event-free survival (EFS)
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Abbotsford
country: Canada
facility: Abbotsford Centre
state: British Columbia
city: Prince George
country: Canada
facility: BC Cancer Agency, Centre for the North
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Centre
state: British Columbia
city: Victoria
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southern Ontario at Kingston
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Centre
state: Ontario
city: Oshawa
country: Canada
facility: R.S. McLaughlin Durham Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Laval
country: Canada
facility: Centre integre de sante et de services sociaux de laval (CISSS de Laval)
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hopital Notre Dame
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Quebec city
country: Canada
facility: CHUQ - Pavillon Hotel-Dieu de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS - Hopital Fleurimont
state: Quebec
city: Regina
country: Canada
facility: The Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Ontario Clinical Oncology Group (OCOG)
name: Tim Whelan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Cancer Agency (BCCA)
name: Sally Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: