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Aim. The aim of our study was to assess the accuracy of a combination of digital mammography and breast ultrasonography in the prediction of response to neoadjuvant systemic treatment in breast cancer patients with different tumor subtypes. Methods. The study was designed as a retrospective diagnostic accuracy study. Stage I-III female breast cancer patients who received any type of neoadjuvant systemic treatment with radiological response assessment by both mammography and breast ultrasound and followed by surgical treatment in the breast and axilla were included in the study. The primary outcome was the diagnostic accuracy of combined modalities of mammography and breast ultrasonography for predicting the pathological complete response. On mammography and breast ultrasonography, the radiological response was categorized into complete response and non-complete response. Pathological complete response on surgical specimens was described based on current guidelines. True and false positive cases as well as true and false negative cases were counted and compared among patients with 4 different molecular subtypes. The diagnostic accuracy of combined imaging modalities was analyzed for positive and negative predictive values, sensitivity, and specificity rates. All rates were calculated according to the previously described formulas. Results. Eighty-one breast cancer cases were included in the study. Positive predictive values of imaging were 100%, 75%, 100%, and 83%, whereas negative predictive values were 67%, 75%, 100%, and 100% in patients with HR+/HER2-, HR+/HER2+, HR-/HER2+ and HR-/HER2- tumors, respectively. Sensitivity rates were found to be 98%, 90%, 100%, and 100%, whereas specificity rates were 100%, 50%, 100%, and 67% in patients with HR+/HER2-, HR+/HER2+, HR-/HER2+ and HR-/HER2- tumors, respectively. Conclusion. Digital mammography and breast ultrasonography as a combined modality seem to show the pathological complete response after neoadjuvant systemic treatment in HR+/HER2- breast cancer patients with a very high specificity rate. Therefore, these conventional tools may help surgeons to select patients who might benefit from loco-regional treatment de-escalation with higher accuracy. [ABSTRACT FROM AUTHOR]