MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer.

PURPOSE: Overexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer. METHODS: miR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease. Response was defined as a Ki67 ≤2.7% after 21±3 days of treatment. The prognostic role of miR-100 expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) breast cancer datasets. Additionally, we explored the correlation between miR-100 and the expression its targets reported as being associated with endocrine resistance. Finally, we evaluated whether a signature based on miR-100 and its target genes could predict the luminal A molecular subtype. RESULTS: Baseline miR-100 was significantly anticorrelated with baseline and post-treatment Ki67 (p<0.001 and 0.004, respectively), and independently associated with response to treatment (OR 3.329, p=0.047). In the METABRIC dataset, high expression of miR-100 identified women with luminal A tumours treated with adjuvant endocrine therapy with improved overall survival (HR 0.55, p<0.001). miR-100 was negatively correlated with PLK1, FOXA1, mTOR and IGF1R expression, potentially explaining its prognostic effect. Finally, a miR-100-based signature developed in patients enrolled in the prospective study outperformed Ki67 alone in predicting the luminal A phenotype. CONCLUSIONS: Our findings suggest that miR-100 should be further explored as a biomarker in patients with luminal breast cancer.

Reoperation rate after breast conserving surgery as quality indicator in breast cancer treatment: A reappraisal.

AIM: To analyse the role of repeated breast surgery (RBS) after breast conserving surgery (BCS) as a quality indicator in a consecutive series of breast cancer patients. METHODS: Data from 1233 breast cancer patients submitted to BCS from 2015 to 2019 were reviewed. The influence of several variables on RBS rate (182/1232; 14.8%) was examined. Univariate and multivariate analyses were conducted to look for significant associations with the risk of RBS. RESULTS: Surgical workload, BCS rate and clinicopathological variables were consistent over the study period, while RBS rate decreased after the introduction of shaving of cavity margins (from 17.9% to 9.5%). Tumor persistence at RBS was higher for mastectomy vs. re-excision (87.3% vs. 37.8%; p = 0.05), inconclusive vs. positive diagnostic biopsy (48.2% vs. 69.4%; p = 0.003), ductal carcinoma in situ vs. invasive carcinoma (69.0% vs. 51.3%; p = 0.046) and lower after neoadjuvant therapy (14.3% vs. 57.8%; p = 0.044). Several clinicopathological variables were associated with the risk of RBS, but only multifocality [Odds Ratio (OR): 1.8; p = 0.009], microcalcifications (OR: 2.0, p = 0.000), neoadjuvant therapy (OR: 0.4; p = 0.014), pathological intraoperative assessment (OR: 0.6; p = 0.010) and shaving of cavity margins (OR: 0.3; p = 0.000) retained independent value at multivariate analysis. CONCLUSIONS: RBS rate can be reduced by shaving of cavity margins. Current standards for RBS should not be made more stringent due to the existence of non-actionable risk factors. The value of RBS as a quality indicator should be scrutinzed.

Diagnostic accuracy of commercial system for computer-assisted detection (CADx) as an adjunct to interpretation of mammograms.

PURPOSE: To evaluate the diagnostic accuracy of the commercial computer-aided detection CADx system for the reading of mammograms. MATERIALS AND METHODS: The study assessed the Second Look system developed and marketed by CADx Medical Systems, Montreal, Canada. The diagnostic sensitivity was evaluated by means of a retrospective study on 98 consecutive cancers detected at screening by double independent reading. The specificity and the positive predictive value (PPV) for cancer of the CADx system were prospectively evaluated on a second group of 560 consecutive mammograms of asymptomatic women not included in screening program. The radiologist who was present during the test assessed the abnormal mammographic findings by one or more of the following diagnostic procedures: physical examination, additional mammographic detail views with or without magnification, ultrasonography, ultrasound- or mammography-guided fine needle aspiration cytology, and core-biopsy. The exams first underwent conventional reading and then a second reading carried out with the aid of the CADx system. RESULTS: The overall diagnostic sensitivity of the CADx system on the 98 screening cancers was 81.6%; in particular it was 89.3% for calcifications, 83.9% for masses and only 37.5% for architectural distortion. The CADx markings for each mammography were 4.7 on average. Identification of invasive carcinoma was independent from tumour size. In the second group of 560 mammograms, the CADx system marked all cases identified as positive by conventional reading and confirmed by biopsy (7/7), but did not permit the detection of any additional cancer. The CADx markings per exam were 4.2 on average, the specificity was 13.7% and the PPV was 0.55% versus 13.7% recall rate of conventional reading. CADx reading led to a 1.96% (11/560) increase of the women necessitating further diagnostic investigation. CONCLUSIONS: The results of our study show that the diagnostic sensitivity of the CADx system is lower than that obtained by double independent reading at screening. Used in association with conventional reading of mammograms of asymptomatic women the CADx system did not increase diagnostic sensitivity.