Abstract Objective: There are currently no nonsurgical options offered to patients with DCIS. The purpose of this study was to assess clinical outcome in a cohort of women declining surgery for pathologically proven ductal carcinoma in situ (DCIS) who have opted for endocrine therapy and clinical/radiographic follow-up.Methods: Between 2003 and 2008, 52 women with ER-positive DCIS enrolled in an IRB-approved single-arm study of 3 months of neoadjuvant enodocrine therapy. The study design included definitive surgical excision. However, 9 women withdrew from the parent study at completion of 3 months and declined surgery, opting instead for a plan of active surveillance, with the intent to proceed with conventional therapy in the event of disease progression or radiographic suspicion for invasive disease. All women were amenable for follow up every 6 months with diagnostic mammography and breast MRI, and wished to continue endocrine therapy, despite unproven benefit in this setting. Endocrine treatment consisted of tamoxifen for premenopausal women or an aromatase inhibitor for postmenopausal women. Each patient was informed of the current treatment guidelines for DCIS, as well as the increased future probability for invasive cancer in the absence of standard treatment for DCIS.Results: The median age of the cohort was 48 years (41-60 years) at enrollment. Of these, 5 women were premenopausal on Tamoxifen, and 4 were post menopausal (3 on letrozole and 1 on arimidex). At the time of analysis, median follow up was 23 months (range 9-66 months). During follow up, 4 patients proceeded with surgery either electively (1 patient) or due to changes at imaging (3 patients). Two of these patients had node-negative invasive breast carcinoma identified at surgery, measuring 6 mm and 4 mm. Five patients have elected to continue surveillance (median follow up 34 months; range 10-66 months), and have had either stable disease or continued regression based on both mammographic and MRI criteria. Four patients remain on endocrine therapy. The patient with longest follow up has had almost complete resolution of radiographic abnormalities at 6 years of surveillance.Conclusion: In this pilot cohort, two-thirds of women who continued endocrine therapy and surveillance for ER-positive DCIS had radiographically stable disease or regression with short-term follow up. Women who initially declined surgery elected to undergo excision in the face of radiographic progression. Active surveillance with endocrine therapy for ER-positive DCIS is feasible, and a well-informed patient cohort is essential to minimize risk. The impact of such an approach on long-term morbidity is unknown, but requires further investigation. Ongoing efforts to improve the detection of invasive cancer in women with DCIS are expected to facilitate such an approach. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 954.