Abstract Background: Surgery, followed by appropriate adjuvant therapy, remains the optimal management for women with early breast cancer. However a significant proportion of elderly patients are either unfit, or less commonly, unwilling to undergo surgery. Primary endocrine therapy (PET) is an option in these women when the carcinoma is oestrogen/progesterone receptor positive. Tamoxifen has been shown to be a successful treatment strategy for these patients. Aromatase inhibitors (AI) are better than tamoxifen with regards to disease-free survival in the adjuvant setting, but the role of these drugs as PET in early breast cancer is not well studied. We reviewed our experience of using Letrozole, an AI, as PET with regards to survival and tumour response. Methods: The records of all patients with newly diagnosed histologically confirmed (by core biopsy) early (non-metastatic) oestrogen and/or progesterone receptor positive breast cancer treated with letrozole from February 2001 to September 2009 were reviewed. Inoperable and locally advanced tumours at presentation were excluded. Reasons for offering PET (rather than surgery), survival, cause of death, time taken to achieve a tumour response, time to achieve the best tumour response obtained with letrozole and failure rate after initial response were studied. Results: 104 patients met the inclusion criteria. Median age was 83 years (58-98). Five cancers were screen-detected and 99 presented symptomatically. The reasons for PET were frailty (n=48), significant comorbidity (n=30), old age (n=9), and patient preference (n=17). Median follow-up (time from diagnosis to death or date of censoring, n=104) was 56 months (4-106) and median overall survival was 35 months (4-103). Fifty five patients were alive at the time of censoring; 38 still on letrozole. Among 49 deaths 12 were from breast cancer, 30 from other causes and cause unknown in 7. 85 cancers (82%) responded to letrozole (stable disease (SD, n=19), partial response (PR, n=42) and complete response (CR, n=24)). The median time to show an initial response (PR or CR) was 4.5 months (2-24). The median time to achieve the best response with letrozole was 8.5 months (3-50). 60 of 85 patients who responded remained on letrozole as sole therapy until death or date of censoring. Letrozole was stopped in others (n= 25) due to progressive disease following an initial response (n=19), side-effects (n=5) and patient choice (n=1). Discussion: Elderly patients with hormone receptor positive breast cancer treated with letrozole as PET have a median survival of approximately 3 years, but breast cancer is not the main cause of death. Most die of associated comorbidity or age, the reason surgery was not offered initially. It takes 4.5 to 8.5 months of treatment to see an initial response and achieve the best response respectively so letrozole therapy should be given for an adequate length of time before its efficacy is assessed. This is one of the first studies examining the effect of letrozole as PET in hormone receptor positive early breast cancer and suggests letrozole is a reasonable alternative to surgery in elderly and unfit patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-12.