RapidET: a MEMS-based platform for label-free and rapid demarcation of tumors from normal breast biopsy tissues

The rapid and label-free diagnosis of malignancies in ex vivo breast biopsy tissues has significant utility in pathology laboratories and operating rooms. We report a MEMS-based platform integrated with microchips that performs phenotyping of breast biopsy tissues using electrothermal sensing. The microchip, fabricated on a silicon substrate, incorporates a platinum microheater, interdigitated electrodes (IDEs), and resistance temperature detectors (RTDs) as on-chip sensing elements. The microchips are integrated onto the platform using a slide-fit contact enabling quick replacement for biological measurements. The bulk resistivity (ρB), surface resistivity (ρS), and thermal conductivity (k) of deparaffinized and formalin-fixed paired tumor and adjacent normal breast biopsy samples from N = 8 patients were measured. For formalin-fixed samples, the mean ρB for tumors showed a statistically significant fold change of 4.42 (P = 0.014) when the tissue was heated from 25 °C to 37 °C compared to the adjacent normal tissue, which showed a fold change of 3.47. The mean ρS measurements also showed a similar trend. The mean k of the formalin-fixed tumor tissues was 0.309 ± 0.02 W m−1 K−1 compared to a significantly higher k of 0.563 ± 0.028 W m−1 K−1 for the adjacent normal tissues. A similar trend was observed in ρB,ρS, and k for the deparaffinized tissue samples. An analysis of a combination of ρB, ρS, and k using Fisher’s combined probability test and linear regression suggests the advantage of using all three parameters simultaneously for distinguishing tumors from adjacent normal tissues with higher statistical significance.

A Model to Predict Upstaging to Invasive Carcinoma in Patients Preoperatively Diagnosed with Low-Grade Ductal Carcinoma In Situ of the Breast

Background: We aimed to create a model of radiological and pathological criteria able to predict the upgrade rate of low-grade ductal carcinoma in situ (DCIS) to invasive carcinoma, in patients undergoing vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. Methods: A total of 3100 VABBs were retrospectively reviewed, among which we reported 295 low-grade DCIS who subsequently underwent surgery. The association between patients’ features and the upgrade rate to invasive breast cancer (IBC) was evaluated by univariate and multivariate analysis. Finally, we developed a nomogram for predicting the upstage at surgery, according to the multivariate logistic regression model. Results: The overall upgrade rate to invasive carcinoma was 10.8%. At univariate analysis, the risk of upgrade was significantly lower in patients with greater age (p = 0.018), without post-biopsy residual lesion (p < 0.001), with a smaller post-biopsy residual lesion size (p < 0.001), and in the presence of low-grade DCIS only in specimens with microcalcifications (p = 0.002). According to the final multivariable model, the predicted probability of upstage at surgery was lower than 2% in 58 patients; among these 58 patients, only one (1.7%) upstage was observed, showing a good calibration of the model. Conclusions: An easy-to-use nomogram for predicting the upstage at surgery based on radiological and pathological criteria is able to identify patients with low-grade carcinoma in situ with low risk of upstaging to infiltrating carcinomas.

Contrast enhanced spectral mammography (CESM) guided breast biopsy as an alternative to MRI guided biopsy

Objective: Contrast Enhanced Spectral Mammography (CESM) breast biopsy has been recently introduced into clinical practice. This short communication describes the technique and potential as an alternative to MRI guided biopsy. Methods and materials: An additional abnormality was detected on a breast MRI examination in a patient with lobular carcinoma. The lesion was occult on conventional mammography, tomosynthesis and ultrasound and required histological diagnosis. Traditionally this would have necessitated a MRI guided breast biopsy, but was performed under CESM guidance. Results: A diagnostic CESM study was performed to ensure the lesion visibility with CESM and then targeted under CESM guidance. A limited diagnostic study, CESM scout and paired images for stereotactic targeting were obtained within a 10 min window following a single injection of iodinated contrast agent. The time from positioning in the biopsy device to releasing compression after biopsy and marker clip placement was 15 min. The biopsy confirmed the presence of multifocal breast cancer. Conclusion: CESM guided breast biopsy is a new technique that can be successfully used as an alternative to MRI guided breast biopsy. Advances in knowledge: CESM guided biopsy can be used to sample breast lesions which remain occult on standard mammography and ultrasound.

Imaging and pathologic features of non-calcified ductal carcinoma in situ: can sonography predict upgrade?

Objectives: The purpose of this study was to evaluate the imaging and pathologic features and upgrade rate of non-calcified ductal carcinoma in situ (NCDCIS). The study tested the hypothesis that lesions with sonographic findings have higher upgrade rate compared to lesions seen on mammography or MRI only. Methods: This retrospective study included patients with ductal carcinoma in situ diagnosed by image-guided core breast biopsy from December 2009 to April 2018. Patients with microcalcifications on mammography or concurrent ipsilateral cancer on core biopsy were excluded. An upgrade was defined as surgical pathology showing microinvasive or invasive cancer. Results: A total of 71 lesions constituted the study cohort. Sixty two percent of cases (44/71) had a mammographic finding, and 38% (27/71) of mammographically occult lesions had findings on either ultrasound, MRI, or both. Of the 67 cases that underwent sonography, a mass was noted in 56/67 (83.6%) cases and no sonographic correlate was identified in 11/67 (16.4%) cases. Twenty-one percent (15/71) of lesions were upgraded on final surgical pathology. The upgrade rate of patients with sonographic correlate was 27% (15/56) versus with mammographic findings only was 0% (0/11). Conclusion: Ductal carcinoma in situ (DCIS) should be considered in the differential diagnosis of architectural distortion, asymmetries, focal asymmetries, and masses, even in the absence of microcalcifications. NCDCIS diagnosed by ultrasound may be an independent risk factor for upgrade. Advances in knowledge: Radiologists must be aware of imaging features of DCIS and consider increased upgrade rate when NCDCIS is diagnosed by ultrasound.

Development of a hoRizontal data intEgration classifier for NOn-invasive early diAgnosis of breasT cancEr: the RENOVATE study protocol

IntroductionStandard procedures aimed at the early diagnosis of breast cancer (BC) present suboptimal accuracy and imply the execution of invasive and sometimes unnecessary tissue biopsies. The assessment of circulating biomarkers for diagnostic purposes, together with radiomics, is of great potential in BC management.Methods and analysisThis is a prospective translational study investigating the accuracy of the combined assessment of multiple circulating analytes together with radiomic variables for early BC diagnosis. Up to 750 patients will be recruited at their presentation at the Diagnostic Senology Unit of Ospedale Policlinico San Martino (Genoa, IT) for the execution of a diagnostic biopsy after the detection of a suspect breast lesion (t0). Each recruited patient will be asked to donate peripheral blood and urine before undergoing breast biopsy. Blood and urine samples will also be collected from a cohort of 100 patients with negative mammography. For cases with histological diagnosis of invasive BC, a second sample of blood and urine will be collected after breast surgery. Circulating tumour DNA, cell-free methylated DNA and circulating proteins will be assessed in samples collected at t0 from patients with stage I–IIA BC at surgery together with those collected from patients with histologically confirmed benign lesions of similar size and from healthy controls with negative mammography. These analyses will be combined with radiomic variables extracted with freeware algorithms applied to cases and matched controls for which digital mammography is available. The overall goal of the present study is to develop a horizontal data integration classifier for the early diagnosis of BC.Ethics and disseminationThis research protocol has been approved by Regione Liguria Ethics Committee (reference number: 2019/75, study ID: 4452). Patients will be required to provide written informed consent. Results will be published in international peer-reviewed scientific journals.Trial registration numberNCT04781062.

Malignancy risk of indeterminate mammographic calcification in symptomatic breast clinics

BackgroundTo explore the potential risk factors predicting malignancy in patients with indeterminate incidental mammographic microcalcification and to evaluate the short-term risk of developing malignancy.MethodsBetween January 2011 and December 2015, one hundred and fifty (150) consecutive patients with indeterminate mammographic microcalcifications who had undergone stereotactic biopsy were evaluated. Clinical and mammographic features were recorded and compared with histopathological biopsy results. In patients with malignancy, postsurgical findings and surgical upgrade, if any, were recorded. Linear regression analysis (SPSS V.25) was used to evaluate significant variables predicting malignancy. OR with 95% CIs was calculated for all variables. All patients were followed up for a maximum of 10 years. The mean age of the patients was 52 years (range 33–79 years).ResultsThere were a total of 55 (37%) malignant results in this study cohort. Age was an independent predictor of breast malignancy with an OR (95% CI) of 1.10 (1.03 to 1.16). Mammographic microcalcification size, pleomorphic morphology, multiple clusters and linear/segmental distribution were significantly associated with malignancy with OR (CI) of 1.03 (1.002 to 1.06), 6.06 (2.24 to 16.66), 6.35 (1.44 to 27.90) and 4.66 (1.07 to 20.19). The regional distribution of microcalcification had an OR of 3.09 (0.92 to 10.3), but this was not statistically significant. Patients with previous breast biopsies had a lower risk of breast malignancy than patients with no prior biopsy (p=0.034).ConclusionMultiple clusters, linear/segmental distribution, pleomorphic morphology, size of mammographic microcalcifications and increasing age were independent predictors of malignancy. Having a previous breast biopsy did not increase malignancy risk.