Abstract OT1-12-01: Exploration of factors associated with imminent risk of late recurrence in hormone receptor positive breast cancer
Authors: Jerzak KJ , Cescon DW , Chia SK , Bratman S , Ennis M , Stambolic V , Chang M , Dowling R , Goodwin PJ 
Published: May 2019

Abstract
Research objectives: To conduct a prospective observational study of patient and tumor-related factors in women with high risk hormone receptor (HR)+/HER2- breast cancer (BC) following at least 5 years of adjuvant hormonal therapy, in order to identify risk factors for imminent recurrence.
Rationale: Many of the life-threatening BC recurrences in women with HR+HER2- BC take place more than 5 years post-diagnosis, often after completion of adjuvant hormonal therapy. The identification of a biomarker(s) for late BC recurrence could lead to interventional trials to evaluate preventive therapies. We will evaluate whether the presence of blood-based biomarkers [(i) Circulating Tumor Cells (CTCs), (ii) circulating tumor DNA (ctDNA), (iii) tumor markers (CA 15-3, CEA)] and patient factors may predict BC recurrence.
Trial design: A prospective cohort of eligible women with previously treated HR+HER2- BC who have not experienced a distant recurrence will be enrolled; patient and circulating factors will be measured annually until distant recurrence or study completion. Host factors (including BMI, lifestyle, medical illness, surgery, trauma and stress, as well as circulating PlGF, VEGF-1 and inflammatory markers) that may contribute to exit of BC cells from dormancy will also be assessed.
The primary outcome is distant BC recurrence. Any BC event, including loco-regional recurrence, new breast or other primary cancer will be evaluated as a secondary endpoint. Outcomes will be ascertained by regular self-report (via annual telephone calls) and/or physician report and confirmed by medical record review.
Key eligibility criteria: i) Diagnosis of ER and/or PR positive (either or both 10% positive), HER2 negative invasive BC, ii) predicted &gt;1.5-2% annual risk of recurrence (T2, T3 or T4 with any N+;T1 N2+; T2N0 or T1 N1 cancers with high risk genomic scores), iii) receipt of adjuvant endocrine therapy for at least 4 years, with discontinuation planned in the next 12 months or completion of endocrine therapy within the last 5 years, iv) prior adjuvant chemotherapy, targeted therapy and bone targeted therapies are allowed provided they have been completed.
Specific aims: 1) Determine if the presence of (i) CTCs, (ii) ctDNA, (iii) CA15-3 and CEA are associated with imminent risk (within 1-2 years) of distant recurrence in the study population. 2) Identify host factors associated with these blood-based biomarkers, as well as clinical outcomes.
Statistical methods: A matched case control design (matching for time since completion of adjuvant hormone therapy, baseline T, N and grade) will be used to investigate associations of key study variables with imminent risk of distant recurrence within the next 1-2 years. Measurements of patients who do versus do not recur will be compared over the 1-2 years prior to relapse. Each variable will be allocated one third of a study-wide type one error of 0.05 (2-sided). ROC analyses and multivariable modelling will be used to optimize sensitivity, specificity, PPV and NPV. Available questionnaire data will be summarized at all time-points to generate descriptive survivorship data.
Accrual: Starting in August 2018, we plan to recruit 1,000 patients over 2 years at selected Canadian cancer centres.
Citation Format: Jerzak KJ, Cescon DW, Chia SK, Bratman S, Ennis M, Stambolic V, Chang M, Dowling R, Goodwin PJ. Exploration of factors associated with imminent risk of late recurrence in hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-12-01.