A Prospective Cohort Study Evaluating Risk of Local Recurrence Following Breast Conserving Surgery and Endocrine Therapy in Low Risk Luminal A Breast Cancer
60 Years
N/A
Female
Breast Cancer
Trial Information
A Prospective Cohort Study Evaluating Risk of Local Recurrence Following Breast Conserving Surgery and Endocrine Therapy in Low Risk Luminal A Breast Cancer
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 = 60 years,
tumours < or = 2cm, excision margin > or = 2mm 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.
Inclusion Criteria:
1. Female patient > or = 60 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 and PR positive and HER2 negative (as determined by an accredited
laboratory);
3. Treated by BCS with microscopically clear resection margins > or = 2mm 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.
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% consistent with the luminal B subtype
Type of Study:
Observational
Study Design:
Observational Model: Cohort, Time Perspective: Prospective
Outcome Measure:
Ipsilateral Breast Tumour Recurrence (IBTR)
Outcome Description:
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.
Outcome Time Frame:
5 years
Safety Issue:
No
Principal Investigator
Tim Whelan, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ontario Clinical Oncology Group (OCOG)
Authority:
Canada: Health Canada
Study ID:
OCOG-2012-LUMINA
NCT ID:
NCT01791829
Start Date:
March 2013
Completion Date:
Related Keywords:
- Breast Cancer
- Luminal A
- Ipsilateral Breast Tumour Recurrence
- Breast Neoplasms
- Recurrence
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