Radiomics for the Discrimination of Infiltrative vs In Situ Breast Cancer

Breast cancer is the most common malignant tumor in women worldwide. Its early diagnosis relies on radiology and clinical evaluation, supplemented by biopsy confirmation. Technological advances in medical imaging, especially in the field of artificial intelligence, allow to address clinical challenges in cancer detection and classification, as well as in the assessment of treatment response, and in monitoring disease progression. Radiomics allows to extract features from images, related to tumor size, shape, intensity, and texture, providing comprehensive tumor characterization. In this paper, we briefly review some Radiomics approaches in breast cancer, focusing on the non-invasive distinction between in-situ and infiltrating breast tumors, and present a preliminary test using Radiomics signatures in DCE-MRI and machine learning, aimed to investigate the feasibility of distinguishing infiltrating cancer from ductal carcinoma in situ (DCIS) diagnosed by preoperative core needle biopsy

Artificial Neural Networks (ANN) for automatic detection of dendritic-shaped cancer cells of cutaneous melanoma in Reflectance Confocal Microscopy (RCM) images

Melanoma (MM) is one of the tumors with the highest incidence. In Italy, MM affected about 13,700 patients out of 373,000 new cases of cancer in 2018, with prognosis dependent on the degree of tumor invasion and presence of metastasis at diagnosis: only an early detection can lead to a better prognosis. Recent evidence suggests that MM is a family of different tumors with varying abilities to grow and metastasize: dendritic-shaped tumor cells were typically found in thin MM in situ. Reflectance Confocal Microscopy (RCM) is a non-invasive imaging tool that enables in vivo observation of the skin at a quasi-histological resolution, providing transverse-section grayscale images related to refractive index of different tissues. In this work, a dataset of RCM images, from 13 healthy subjects and 22 patients affected by MM in situ, were used to train a Multi-Layer Perceptron (MLP) artificial neural network. Each image was subdivided into sub-blocks, labeled as positive if containing significant clusters of dendritic-shaped tumour cells. In each block, various standard features were calculated, e.g. Haralick's and features from the run-length matrices. The MLP was trained to recognize the presence of clusters of dendritic-shaped cancer cells. The preliminary results are encouraging, giving AUC=0.81 with about 73% accuracy. Tests are currently underway to improve quality

Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

Càncer de mama; Genòmica del càncer; Recerca translacionalCáncer de mama; Genómica del cáncer; Investigación traslacionalBreast cancer; Cancer genomics; Translational researchNovel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.This work was supported by the grants from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement No. 847912 (to A.P.), the Instituto de Salud Carlos III-PI16/00904 (to A.P.), Pas a Pas (to A.P.), Save the Mama (to A.P.), Breast Cancer Now-2018NOVPCC1294 (to A.P.), Fundación Científica Asociación Española Contra el Cáncer-Ayuda Postdoctoral AECC 2017 (to F.B.-M.), Fundación SEOM, Becas FSEOM para Formación en Investigación en Centros de Referencia en el Extranjero 2018 (to T.P.) and PhD4MD - Departament de Salut expedient SLT008/18/00122 (to N.C.)

The effects of the COVID19-related lockdown are modulated by age: an Italian study in toddlers and pre-schoolers

Although the issue has been repeatedly explored, data on the impact of the COVID-19 pan- demic on children’s sleep quality are inconsistent. To clarify these discrepancies, here we investigate possible age-related differences. During the lockdown, 112 parents of toddlers (0–3 years, N = 61) and pre-schoolers (4–5 years, n = 51) completed an online survey including the Children’s Sleep Habits Questionnaire (CSHQ). Sleep-related items required an additional retrospective judgment, referring to the pre-pandemic period. During the lockdown, sleep schedules were delayed in both age groups whereas sleep quality (CSHQ total scores) improved in pre-schoolers but not in toddlers. Between-groups comparisons revealed that, prior to the lockdown, pre-schoolers showed worse sleep quality than toddlers, whereas this difference disappeared during home confinement. Also, pre-schoolers’ sleep timing was advanced before the lockdown and delayed during the lockdown relative to toddlers’. Our data highlight a significant modulation of age on the impact of the pandemic crisis on sleep, with pre-schoolers experiencing greater effects than toddlers. This profile suggests that factors affecting sleep features have different weights at different ages: sleep patterns would be mainly determined by developmental factors (i.e., biological drive) in younger children, whereas environmental factors (e.g., major lifestyle changes) would have a stronger effect on older ones

Management of young women with early breast cancer

Breast cancer is still the most frequent cancer diagnosed in women aged 6440 years and the primary cause of death in this age group. The management of these patients needs a dedicated approach involving a multidisciplinary team that takes into account their treatment and survivorship issues. The present review aims to provide a perspective on the many challenges associated with treatment of young women with early breast cancer. We will focus on the standard (neo)adjuvant treatment, highlighting the paucity of age-specific results about the available genomic signatures, the groundbreaking landscape of adjuvant endocrine therapy and the relevant issue of the fertility preservation

Potential Mechanisms of Ovarian Protection with Gonadotropin-Releasing Hormone Agonist in Breast Cancer Patients: A Review

The use of chemotherapy in premenopausal cancer patients may lead to chemotherapy-induced premature ovarian failure. Pharmacological temporary ovarian suppression obtained with the gonadotropin-releasing hormone agonist (GnRHa) administered concomitantly with chemotherapy has been investigated as a technique capable to reduce the gonadotoxicity, reducing the risk of developing premature menopause. In recent years, important evidence has become available on the efficacy and safety of this strategy that should now be considered a standard option for ovarian function preservation in premenopausal breast cancer patients. However, in women interested in fertility preservation, this is not an alternative to cryopreservation strategies, which remains the first option to be proposed. The purpose of this review is to summarize the mechanisms of GnRHa in the preservation of fertility in premenopausal cancer patient candidates to receive chemotherapy, highlighting the areas of doubt that require further investigation

Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: a systematic review and meta-analysis

Single-agent poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved as the first targeted therapy available for patients with BRCA-mutated HER2-negative metastatic breast cancer. This meta-analysis aimed to better evaluate activity, efficacy and safety of single-agent PARPi in this population. A systematic search of Medline, Embase and conference proceedings up to 31 January 2018 was conducted to identify randomised controlled trials (RCTs) investigating single-agent PARPi versus monochemotherapy in patients with BRCA-mutated HER2-negative metastatic breast cancer. Using the random-effect model, we calculated summary risk estimates (pooled HR and OR with 95% CI) for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), any grade and grade 3-4 adverse events (AEs), treatment discontinuation rate and time to deterioration in quality of life (QoL). Two RCTs (n=733) were included. As compared with monochemotherapy, single-agent PARPi significantly improved PFS (HR 0.56(95% CI 0.45 to 0.70)) and ORR (OR 4.15 (95% CI 2.82 to 6.10)), with no difference in OS (HR 0.82 (95% CI 0.64 to 1.05)). Single-agent PARPi significantly increased risk of anaemia and any grade headache, but reduced risk of neutropenia and any grade palmar-plantar erythrodysesthesia syndrome as compared with monochemotherapy. No significant differences in other AEs and treatment discontinuation rate were observed. Patients treated with PARPi experienced a significant delayed time to QoL deterioration (HR 0.40 (95% CI 0.29 to 0.54)). Single-agent PARPi showed to be an effective, well tolerated and useful treatment in maintaining QoL of patients with BRCA-mutated HER2-negative metastatic breast cancer

The role of dose-dense (DD) adjuvant chemotherapy (CT) in HER2-positive (HER2+) early breast cancer (BC) patients (pts) before and after the introduction of trastuzumab (T): Exploratory analysis of the GIM2 trial

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Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/HER2‐negative metastatic breast cancer: systematic review and meta‐analysis

A precise assessment of the efficacy of first‐/second‐line endocrine therapies (ET) ± target therapies (TT) in clinically‐relevant subgroups of hormone receptor‐positive (HR+)/HER2‐negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision‐making, we thus conducted a systematic literature search to identify all first‐/second‐line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta‐analysis to assess progression‐free (PFS) and/or overall survival (OS) benefit in several clinically‐relevant prespecified subgroups. Thirty‐five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26–41% and 12–27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single‐agent ET (PFS hazard ratio (HR) range for combinations: 0.60–0.65 vs. HR range for single agent ET: 0.59–1.37; OS HR range for combinations: 0.74–0.87 vs. HR range for single agent ET: 0.68–0.98), with CDK4/6‐inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in nonvisceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi‐based combinations proved to be a valid therapeutic option in endocrine‐resistant tumors, as well as PI3Ki + ET in PIK3CA‐mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision‐making