Abstract P5-13-07: An investigator-initiated registry trial of simple oral therapy for low risk breast cancer
Authors: Gadi VK , Preusse C , Calhoun KE , Kim J , Linden HM , Rendi M , Etzioni RB , Gooley T , Lyman G , Stork L , van der Baan B , Barth N , Rahbar H 
Published: May 2016

Abstract
Background: Across multiple studies performed in several countries with widely instituted screening mammography programs at different intervals between exams, up to 19% of breast cancer identified is in patients whose disease would otherwise go undetected and not have caused any ill effect if left untreated. Recent advances in pathologic and multigene assays have demonstrated promise to better identify low risk breast cancer and appropriately tailor treatments. Nonetheless, most women who may have such low-risk, estrogen receptor expressing lesions continue to be offered only an aggressive treatment paradigm. This most commonly includes surgery and lymph node evaluation and, in the case of breast conservation, breast irradiation following surgery, with the option of endocrine therapy for 5-10 years.
Trial design: We propose a multi-center US registry study of post-menopausal, female breast cancer patients age 60 and older who will be managed 5 years with oral endocrine therapy for mammographically screen-detected, node-negative, unifocal invasive disease with low clinical grade, high estrogen/progesterone receptor expression, negative Her2 expression, Ki67 rate &lt;20%, and low-risk multigene expression analysis with Mammaprint Breast Cancer Recurrence Assay. Target lesions will be confirmed with a pre-treatment bilateral breast MRI and imaged routinely with standard mammography or ultrasound at 3-month intervals during months 1-36 and at 6-month intervals during months 37-60 to assess for disease response. Enrolled patients will have an ECOG performance status of 0-2. Medication history will be documented at routine follow-up visits.
Our primary objective will be to determine the frequency of conversion from a low-toxicity approach with oral endocrine therapy to conventional care with surgery +/- radiation therapy as a result of progression of disease or patient/provider choice. Progression of disease will be quantified objectively as &gt;20% growth of the target lesion as compared to baseline in imaging measurements. After 5 years of endocrine therapy sans disease progression, patients may elect to continue or stop treatment or convert to standard care.
Statistical methods: We will determine the conversion rate from oral therapy for any cause to conventional management (compliance). Compared to the most pessimistic assumed true-rate for compliance of 0.5, we predict &gt;90% power to detect a decrease of 0.1 in outcomes with an alpha of 5% (corresponds to a 95% Confidence Interval). Using descriptive statistics, we will also quantify for disease responses and progression-free survival. Our sample size will be ample for multiple sub-analyses including measurement of differences emanating from tertiary care versus local oncologic management, advanced imaging outcomes (if performed on any subset of patients), effect of type of endocrine therapy type (SERM vs AI), and effect of age and/or comorbidity severity interaction.
Accrual: Clinic sites with large patient cohorts are now being selected nationwide to enroll and manage patients' disease with endocrine treatment only. We will select up to 20 sites and enroll 300 patients with low-risk disease.
Citation Format: Gadi VK, Preusse C, Calhoun KE, Kim J, Linden HM, Rendi M, Etzioni RB, Gooley T, Lyman G, Stork L, van der Baan B, Barth N, Rahbar H. An investigator-initiated registry trial of simple oral therapy for low risk breast cancer. [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 P5-13-07.