Abstract OT2-01-01: Endocrine therapy alone as primary treatment for elderly patients with clinical stage I to III estrogen receptor positive breast cancer with low recurrence score
Authors: Aft R , Trinkaus K , Ma C 
Published: May 2016

Background: Approximately 20% of breast cancers are diagnosed in women 75 years of age or older. Elderly patients with breast cancer are at a higher risk for over- or under-treatment. In general, older patients are more likely to die from comorbidities than from their breast cancer. The 21-gene Recurrence Score (RS) predicts 10-year distant recurrence rate in the adjuvant setting in women with early stage ER+ breast cancer. In elderly patients, a large percentage of the cancers diagnosed are ER+. It is likely that a subpopulation of elderly women with good prognosis ER+ tumors can be identified who may benefit from endocrine therapy alone, without surgery, to treat their cancer without compromising clinical outcome. We hypothesize that endocrine therapy alone will provide adequate local and systemic control of breast cancer in the subpopulation of women 75 or older with ER+ breast cancer and low RS.

Trial Design: This is a single arm phase II trial in pts with newly diagnosed early stage ER+ breast cancer, age 75 or greater. RS will be obtained on core biopsies collected at the time of diagnosis. Patients whose scores are &lt; 18 will be enrolled into the trial and receive endocrine therapy only. Patients whose scores are ≥ 18 will receive standard of care (SOC) treatment. Tumor assessment will occur every 6 months. Patient can continue on endocrine therapy for up to 10 years. If there is progression of disease, then an alternative endocrine agent may be prescribed or the patient can opt for SOC treatment.

Objectives: Primary: To determine the rate of loco-regional progression in women with early-stage ER+ breast cancer, 75 years or older with low RS who are treated with endocrine therapy alone. Secondary: To determine the breast cancer-specific survival and overall survival of women with early-stage ER+ breast cancer who are 75 years or older treated with endocrine therapy alone. To correlate response to treatment with RS.

Eligibility: Newly diagnosed invasive breast cancer defined as cT1 or T2, N0-1, M0, age 75 years of age or older and ECOG performance status ≤ 2. Disease must be ER+ (Allred score ≥ 5) and HER2- and measurable defined as lesions that can be accurately measured in at least one dimension by ultrasound or mammogram.

Statistical Methods: A Kaplan-Meier model will be used to estimate the 5-year local or systemic progression rate with a Brookmeyer-Crowley confidence interval. If the true 5-year progression rate is 10%, a sample size of 50 will provide power = .90 at a one-sided .05 significance level to demonstrate that the rate is less than 25.5%. A point estimate of the cumulative incidence of local progression at 5 years will be calculated using a Kaplan-Meier model or, if covariate adjustment is desired, a Cox proportional hazards model. The upper bound of a 95% confidence interval will be used to determine whether the rate may plausibly fall above 25.5%.

Accrual: Target 50 patients with an RS score &lt; 18 will be enrolled. Anticipated opening is July 2015.

Citation Format: Aft R, Trinkaus K, Ma C. Endocrine therapy alone as primary treatment for elderly patients with clinical stage I to III estrogen receptor positive breast cancer with low recurrence score. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-01-01.