Abstract Background: Most women with newly diagnosed breast cancer are of luminal type and will be offered 5-10 years of adjuvant endocrine therapy. Many women will not have a survival benefit from this therapy and 30% or more will struggle with side effects and quality of life issues. Breast Cancer Index (BCI) is a genomic biomarker for early-stage, ER+ breast cancer and has been validated to assess risk of late (5-10 yr) distant recurrence and predict likelihood of benefit from extended (>5y) endocrine therapy utilizing the HoxB13/IL17BR(H/I) ratio. H/I has also been shown to predict benefit from endocrine therapy in the early adjuvant setting. The objective of this study was to characterize the impact of BCI on endocrine therapy decision-making for early-stage breast cancer patients. Methods: Data was collected retrospectively from patients with early-stage luminal breast cancer treated at Breastlink who underwent BCI testing between 10/2014-5/2015. The impact of BCI test results were analyzed for 3 indications: 1) initiation of endocrine therapy for patients considering no adjuvant treatment; 2) patients 6 mo-4y post diagnosis struggling with side effects and desiring to discontinue endocrine therapy; and 3) patients beyond 4 years of adjuvant hormonal therapy deciding whether to extend therapy for an additional 5 years. Results: One hundred patients underwent BCI testing with median age 53 (range 35-77). The BCI assay was utilized in 14 cases at diagnosis, 54 cases at 6 mo-4y during therapy, and 32 cases at >4y post-diagnosis. In patients tested at time of diagnosis, 10/11 that were low risk for late recurrence and low likelihood of benefit from endocrine therapy chose not to initiate therapy, and 2/2 patients were high risk/high likelihood to benefit initiated therapy. One patient, a 72 year-old with low risk and high likelihood to benefit, declined therapy. In patients tested between 6 mo-4y on therapy, 30/30 patients were low risk and low likelihood of benefit chose to stop endocrine therapy, and 11/11 patients were high risk and high likelihood of benefit chose to continue. Of 7 patients that were low risk but high likelihood of benefit, 5 continued therapy. All 6 patients that were high risk but low likelihood of benefit chose to stop therapy. Of 32 patients tested after 4 years of adjuvant therapy, 13/13 were low risk and low likelihood of benefit chose to stop endocrine therapy at 5 years, and 8/8 were high risk and high likelihood of benefit chose to extend therapy to 10 years. All 5 patients that were high risk but low likelihood of benefit elected to stop, and 3/6 patients that were low risk but high likelihood to benefit extended therapy. In total, endocrine therapy treatment decision making aligned with predictive (H/I) results in 93/100 patients. Conclusion: The BCI test was instrumental in assisting almost all women in their decision to receive or maintain adjuvant hormonal therapy and 67% of women discontinued or declined hormonal therapy based on test results. All patients with high risk and high predictive benefit on BCI assay chose to pursue adjuvant endocrine therapy. Oncologists can use BCI in their algorithms of delivering personalized cancer care. Citation Format: Link JS, Buck LJ, Kapoor NS. The breast cancer index as a tool in decision making for adjuvant hormonal therapy in early luminal breast cancer: Initiation, withdrawal and continuance. [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 P5-08-10.