Abstract Introduction: After an enthusiastic and promising start to the large scale use of screening programs for the detection of small in situ breast cancers, an analysis of results from different screening studies has led to disappointing and somewhat alarming conclusions. A problem of over diagnosis has emerged, involving, in many cases, unnecessary treatments, and causing a negative psychological and social impact on patients and a considerable economic burden on Health Services. Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has not been investigated as widely as invasive breast cancer. Today women with in situ breast cancer are mainly treated with conservative surgery and often with radiotherapy, even though the real impact of this treatment is still not known. New diagnostic and therapeutic information is thus needed. Although conventional steroid hormone receptors, cell proliferation and other important tumor markers have been extensively studied in invasive tumors, little is known about the role played by androgen receptors (ARs), widely expressed in DCIS. We previously demonstrated in a series of DCIS patients treated with surgery alone that the AR/estrogen receptor (ER) ratio is an important prognostic marker. In the present study, we analyzed these markers in a series of DCIS patients treated with surgery and radiotherapy. Methods: We performed a retrospective study on a series of 42 DCIS patients treated with quadrantectomy and radiotherapy and followed up for a period ranging from 5 to 13 years to evaluate the prognostic relevance of ER and ARs determined by immunohistochemistry. Results: Our findings showed that AR expression was significantly higher in relapsed patients than in non relapsed patients, and that ER levels were higher in patients who did not relapse with respect to those who did. The AR/ER ratio was significantly different in the two subgroups. Moreover, when the variables were considered singly, area under the curve (AUC) values were 0.85 for ARs, 0.62 for ER and 0.79 for the AR/ER ratio. Conclusions: In agreement with our previous work on a series of DCIS patients treated with surgery alone, the preliminary results from the present study highlight the important role of AR and of the AR/ER ratio as prognostic indicators of relapse in patients treated with surgery and radiotherapy. Our findings also suggest that the treatment used was not capable of controlling disease or of eliminating the risk of recurrence. New avenues for tailored therapy must be sought. Citation Format: Sara Bravaccini, Sara Ravaioli, Maria Maddalena Tumedei, Rosella Silvestrini, Flavia Foca, Ilaria Massa, Roberta Maltoni, Andrea Rocca, Secondo Folli, Federico Buggi, Annalisa Curcio, Maurizio Puccetti, Luigi Serra, Elisabetta Pietri, Daniele Andreis, Alberto Farolfi, Dino Amadori. Clinical relevance of androgen and estrogen receptors in patients with ductal carcinoma in situ of the breast treated with surgery and radiotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr B44.