BackgroundThe focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC).MethodsFirst, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization.ResultsQuantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR).ConclusionOur findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1163-y) contains supplementary material, which is available to authorized users.

!Introduction: Ductal carcinoma in situ (DCIS) is a premalignant lesion of the glandular component of the breast and a precursor lesion of invasive breast cancer. In recent decades the incidence of DCIS has risen continuously, mainly because of more extensive screening and more advanced diagnostic procedures. There is an increasing need for evidence-based treatment guidelines which will protect patients as far as possible from recurrence or invasive cancer but also from overtreatment. This retrospective single-center clinical trial analyzed recurrence-free survival times, rates of invasive and non-invasive events, and the impact of patient history, histopathological variables and therapeutic factors on recurrence-free survival times. Material and Methods: A total of 200 patients who underwent surgery between 2000 and 2007 for pure DCIS were included in the study. As part of follow-up a questionnaire was sent to patients and their respective gynecologists. Results: In the follow-up period, 12.5 % (n = 25) of the 200 patients had recurrence (invasive or noninvasive event). Menopausal status, tumor grade and tumor size were significantly associated with recurrence. Low-grade DCIS was significantly more often hormone receptor-positive than high-grade DCIS. Patients who had postoperative radiotherapy significantly more often also received endocrine drug treatment. There was a significant association between younger patient age and drug treatment. The study found that in the investigated cohort, premenopausal women had a significantly shorter recurrence-free time compared to postmenopausal women. Conclusion: This paper summarizes the current literature on DCIS. There is a need for more prospective clinical trials to improve the prognosis of premenopausal women with large and hormone receptor-positive DCIS. Zusammenfassung

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