Background: The majority of women with early stage breast cancer (BC) will become long-term survivors, living with the sequelae of treatment. Attention to symptoms and quality of life (QoL) are therefore of increasing importance both during treatment and survivorship. Aromatase inhibitors (AIs) are used to treat postmenopausal women with hormone-receptor positive (HR+) BC and can lead to profound urogenital atrophy. Atrophic vaginitis in BC survivors is prevalent, its management is complex and it negatively impacts QoL. Methods: A prospective longitudinal IRB-approved study was performed at MSKCC in26 postmenopausal women with stage I-III HR+ BC on adjuvant letrozole or anastrozole for at least 3 months and had urogenital atrophy. All women were initiated on 10µg intravaginal 17-β estradiol. Patients completed the Female Sexual Function Index (FSFI) and Menopausal Symptom Checklist (MSCL) at baseline and wks 12 & 24. Increase in FSFI score means better sexual function and a decrease in MSCL score means improved symptoms. We used the Wilcoxon Signed Rank Sum test to compare QoL measures at baseline to wks 12 and 24. The primary endpoint was change in systemic estradiol level from baseline to wk 12. Serial estradiol/FSH levels were measured at baseline and wks 2, 7, 12, 18 & 24; we used a highly sensitive estradiol radioimmunoassay, ESTR-US-CT, from Cisbio US, Inc. Herein we report the results from the QoL secondary endpoints. Results: During treatment with intravaginal 17-β estradiol 10mcg, improvement in sexual function as measured by the FSFI was seen from a median of 12.4 at baseline to 21.2 at wk 12 (p=.0091) and 21.8 at wk 24 (p=.0271). Improvement was seen from baseline to wk 12 in lubrication (p=.0091), desire (p=.0303), satisfaction (p=.0331) and pain (p=.0005) and from baseline to wk 24 in lubrication (p=.0210), desire (p=.0309) and orgasm (p=.0369). A reduction in menopausal symptoms was also seen from 30.0 at baseline to 23.6 at wk 12 (p=.01) and 22.5 at wk 24 (p=.003). Conclusions: Intravaginal 10μg 17-β estradiol provided relief from menopausal symptoms and improvement in sexual dysfunction in the domains of lubrication, desire, satisfaction, orgasm, and pain.