Papers by Andrea Vingiani
PLOS Genetics
Background Previous studies have provided a comprehensive picture of genomic alterations in prima... more Background Previous studies have provided a comprehensive picture of genomic alterations in primary and metastatic Hormone Receptor (HR)-positive, Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer (HR+ HER2- BC). However, the evolution of the genomic landscape of HR+ HER2- BC during adjuvant endocrine therapies (ETs) remains poorly investigated. Methods and findings We performed a genomic characterization of surgically resected HR+ HER2- BC patients relapsing during or at the completion of adjuvant ET. Using a customized panel, we comprehensively evaluated gene mutations and copy number variation (CNV) in paired primary and metastatic specimens. After retrieval and quality/quantity check of tumor specimens from an original cohort of 204 cases, 74 matched tumor samples were successfully evaluated for DNA mutations and CNV analysis. Along with previously reported genomic alterations, including PIK3CA, TP53, CDH1, GATA3 and ESR1 mutations/deletions, we found that E...
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Cancer Discovery, 2021
In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of an... more In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor Th1/cytotoxic responses and an enrichment of IFNγ and other immune signatures associated with better clinical outcomes in patients with cancer. Our fi...
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Journal of Experimental & Clinical Cancer Research
Background Molecular tumor boards (MTBs) match molecular alterations with targeted anticancer dru... more Background Molecular tumor boards (MTBs) match molecular alterations with targeted anticancer drugs upon failure of the available therapeutic options. Special and local needs are most likely to emerge through the comparative analysis of MTB networks, but these are rarely reported. This manuscript summarizes the state-of-art of 16 active Italian MTBs, as it emerges from an online survey curated by Alliance Against Cancer (ACC). Main text Most MTBs (13/16) are exclusively supported through local Institutional grants and meet regularly. All but one adopts a fully virtual or a mixed face-to-face/virtual calling/attendance meeting model. It appears that the ACC MTB initiative is shaping a hub-and-spoke virtual MTB network reminiscent of non-redundant, cost-effective healthcare organization models. Unfortunately, public awareness of MTB opportunities presently remains insufficient. Only one center has a website. Dedicated e-mail addresses are for the exclusive use of the MTB staff. More t...
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Frontiers in Oncology
Extramammary Paget disease (EMPD) is a rare form of cutaneous, intraepithelial adenocarcinoma, wh... more Extramammary Paget disease (EMPD) is a rare form of cutaneous, intraepithelial adenocarcinoma, which typically presents itself as an erythematous plaque originating from apocrine-gland rich regions, such as the vulva, the perianal region, the scrotum, the penis, or the axilla. EMPD patients typically have a good prognosis, with expected 5-year survival of 60%–92%, but it is estimated that about one-third of EMPD patients will develop lymph node or distant metastases. Treatment approaches for EMPD include locoregional therapies such as broad surgical resection, radiotherapy, or topical imiquimod, when the disease is localized, and chemotherapy and biological agents for advanced EMPD. We report the case of a 58-year-old man diagnosed with locally advanced, symptomatic HER2-overexpressing, AR-positive EMPD, who achieved long-term tumor control with a sequence of several trastuzumab-based treatments (more than 30 months with second-line carboplatin plus paclitaxel plus trastuzumab follo...
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Scientific Reports
Triple negative breast cancer (TNBC) is characterized by clinical aggressiveness, lack of recogni... more Triple negative breast cancer (TNBC) is characterized by clinical aggressiveness, lack of recognized target therapy, and a dismal patient prognosis. Several studies addressed genomic changes occurring during neoadjuvant chemotherapy (NAC) focusing on somatic variants, but without including copy number alterations (CNAs). We analyzed CNA profiles of 31 TNBC primary tumor samples before and after NAC and of 35 single circulating tumor cells (CTCs) collected prior, during and after treatment by using next-generation sequencing targeted profile and low-pass whole genome sequencing, respectively. In pre-treatment tissue samples, the most common gains occurred on chromosomes 1, 2 and 8, and SOX11 and MYC resulted the most altered genes. Notably, amplification of MSH2 (4/4 versus 0/12, p < 0.01) and PRDM1 and deletion of PAX3 (4/4 versus 1/12, p < 0.01) significantly characterized primary tumors of patients with pathological complete response. All patients with paired pre- and post-N...
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Frontiers in Oncology
Tumour testing of the BRCA1/2 genes is routinely performed in patients with different cancer hist... more Tumour testing of the BRCA1/2 genes is routinely performed in patients with different cancer histological subtypes. To accurately identify patients with tumour-detected germline pathogenic variants (PVs) is a relevant issue currently under investigation. This study aims at evaluating the performance of the tumour-to-germline diagnostic flowchart model defined at our Institutional Molecular Tumour Board (MTB). Results from tumour BRCA sequencing of 641 consecutive unselected cancer patients were discussed during weekly MTB meetings with the early involvement of clinical geneticists for appropriate referral to genetic counselling. The overall tumour detection rate of BRCA1/2 PVs was 8.7% (56/641), ranging from 24.4% (31/127) in high-grade ovarian cancer to 3.9% (12/304) in tumours not associated with germline BRCA1/2 PVs. Thirty-seven patients with PVs (66%) were evaluated by a clinical geneticist, and in 24 of them (64.9%), germline testing confirmed the presence of the PV in blood. ...
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Additional file 1: Table S1. reports Type and distribution of events over time. Table S2. reports... more Additional file 1: Table S1. reports Type and distribution of events over time. Table S2. reports Prognostic factors of early (≤5 years) and late (> 5 years) DFS events in ILCs, univariate and multivariate analysis. Table S3. reports Prognostic factors of late (> 5 years) DFS in ILCs by lymph-node status. Table S4. reports Distribution of patient baseline characteristics according to intrinsic and histological subtype – matched groups. Table S5. reports Prognostic factors of early (≤ 5 years) and late (> 5 years) distant recurrences in IDCs and ILCs, univariable analysis. Table S6. reports the Likelihood ratio test p-value of the addition of HER2, ER, PgR and ln(Ki-67) variables to CTS5 considered as continuous variable. Figure S1. reports Flowchart for patient's selection and matching
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Neoplasma, 2022
PTEN deletion and Ki-67 expression are two of the most promising biomarkers in prostate cancer (P... more PTEN deletion and Ki-67 expression are two of the most promising biomarkers in prostate cancer (PCa). In the same manner, multiparametric magnetic resonance imaging (mp-MRI) guided core biopsy is a powerful tool for PCa detection and staging. The aim of the study is to assess whether a correlation can be identified between the pathological stage defined by an mp-MRI-guided core-biopsy and Ki-67 expression and PTEN deletion. Such correlation might be useful for staging and treatment personalization in PCa. This investigation was conducted in the context of phase II clinical study "Short-term radiotherapy for early prostate cancer with a concomitant boost to the dominant lesion" (AIRC IG-13218), ClinicalTrials.gov identifier: NCT01913717. Nineteen patients underwent a further in-bore MRI-targeted core biopsy (MRI-TBx) on the dominant intraprostatic lesion (DIL); on this basis, an additional Gleason Score (GS) was determined. PTEN loss and Ki-67 expression on these samples were analyzed and correlated with both risk categories modifications and oncological outcomes (overall survival, biochemical and clinical relapse). GS was upgraded in 5 cases, with 4 patients re-classified as intermediate-risk and 1 patient as high-risk. The latter experienced a clinical local relapse. No correlations between up/down-staging, PTEN deletion, and Ki-67 expression were observed in this cohort. Further investigations are needed towards the identification of a pattern in the tumor aggressiveness-response in PCa treated with ultra-hypofractionated radiotherapy. Moreover, a possible relationship between biomarker analysis and imaging textural features could be explored.
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Annals of Oncology, 2019
Background Nivolumab is an established treatment for recurrent/metastatic (RM) head and neck squa... more Background Nivolumab is an established treatment for recurrent/metastatic (RM) head and neck squamous cell carcinoma (HNSCC) patients (pts) failing platinum-based treatment. However, knowledge about safety and activity data are limited to pts enrolled into clinical trial leading to drug approval. Methods We conducted a single-arm, open-label, multicentre prospective phase IIIb clinical trial with nivolumab 240 mg in subjects with RM HNSCC. Primary objective was to assess the incidence of high-grade (CTCAE v 4.03 grade 3 or higher), treatment-related (TR), selected adverse events (AE); secondary objectives were to characterize the outcome of all AE in terms of duration, time to event onset, and event resolution. Moreover, we assessed Overall Response Rate (ORR), OS and PFS and we analysed in an exploratory way clinical and biomolecular factors associated with improved outcome. A subgroup analysis was also performed in 20 pts to define baseline immunologic profiles and their changes a...
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Annals of Oncology, 2019
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Histopathology, 2013
To ascertain the prognostic relevance of micropapillary carcinoma, a specific type of breast tumo... more To ascertain the prognostic relevance of micropapillary carcinoma, a specific type of breast tumour. We interrogated the clinical records of a series of 49 pure micropapillary carcinoma patients and 13 487 invasive ductal carcinoma patients, diagnosed and treated consecutively in our institution over a 9-year time-frame. Compared with invasive ductal carcinoma, patients with micropapillary carcinoma more frequently had moderately differentiated tumours (P = 0.02) with extensive peritumoral vascular invasion (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), associated with a significantly higher rate of axillary lymph node involvement (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Survival data obtained by comparing 49 micropapillary carcinoma patients with a set of 98 invasive ductal carcinoma patients matched for age, tumour size and grade, peritumoral vascular invasion, immunohistochemically defined molecular subtype, number of positive lymph nodes and year of surgery showed that the micropapillary histotype did not add any independent information to the risk of locoregional (P = 0.48) or distant (P = 0.79) relapse, or overall survival (P = 0.60). Our data reinforce the notion that micropapillary carcinoma usually arises as a locally advanced disease, and provide evidence that micropapillary histology does not add any additional information on clinical outcome independent of clinicopathological characteristics such as lymph node status and immunohistochemically defined molecular subtype.
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Endoscopy, 2012
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Cancer Prevention Research, 2012
Background: Metformin has been associated with a significant reduction in cancer incidence and mo... more Background: Metformin has been associated with a significant reduction in cancer incidence and mortality in diabetic patients relative to other antidiabetic drugs, including positive results specifically in breast cancer. In a recent window-of-opportunity trial in 200 non-diabetic women with breast cancer, we showed a heterogeneous effect of metformin on breast cancer proliferation (Ki-67 labeling index) depending on insulin resistance, with a trend to a decreased proliferation in women with insulin resistance (HOMA>2.8) and an opposite trend in women with normal insulin sensitivity (Bonanni et al. JCO 30:2593, 2012). Here we performed an exploratory study to determine whether metformin has antiproliferative effects on adjacent lobular or ductal intraepithelial neoplasia (LIN or DIN) and on distant ductal hyperplasia and whether these effects are different according to specific host and tumor characteristics. Previous studies showed that Ki-67 LI in atypical lesions predicts subs...
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Supplemental material, sj-pdf-1-tam-10.1177_17588359211006960 for Hormone receptor status influen... more Supplemental material, sj-pdf-1-tam-10.1177_17588359211006960 for Hormone receptor status influences the impact of body mass index and hyperglycemia on the risk of tumor relapse in early-stage HER2-positive breast cancer patients by Francesca Ligorio, Luca Zambelli, Achille Bottiglieri, Lorenzo Castagnoli, Emma Zattarin, Riccardo Lobefaro, Arianna Ottini, Andrea Vingiani, Serenella M. Pupa, Giulia V. Bianchi, Giuseppe Capri, Giancarlo Pruneri, Filippo de Braud and Claudio Vernieri in Therapeutic Advances in Medical Oncology
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npj Breast Cancer
The importance of integrating biomarkers into the TNM staging has been emphasized in the 8th Edit... more The importance of integrating biomarkers into the TNM staging has been emphasized in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8th edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.
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npj Breast Cancer
The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved su... more The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences fro...
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Lung squamous cell carcinoma (SCC) has always been considered a monomorphic entity, different fro... more Lung squamous cell carcinoma (SCC) has always been considered a monomorphic entity, different from lung adenocarcinoma which is known to be a very heterogeneous tumor from morphological and molecular point of view. Just two histological subtypes of SCC are recognised, the basaloid and lymphoepithelioma-like histotypes, as in other sites different from the lung. Recently, different studies tried to expand the classification of SCC by adding different subtypes based on morphological characteristics (such as keratinization or clear cell features) or different growth patterns (papillary or basaloid). We report a case of squamous cell carcinoma with a previously unreported, distinctive and predominant “lepidic” growth pattern, with its immunophenotypical and molecular characterization.
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Tumori Journal
Aim: To evaluate the presence of contrast enhancement at the site of calcifications on contrast-e... more Aim: To evaluate the presence of contrast enhancement at the site of calcifications on contrast-enhanced mammography (CEM) and histopathologic results at vacuum-assisted biopsy (VAB), and to examine the association with lesion size and immunohistochemical characteristics, in order to assess disease aggressiveness in malignant lesions. Methods: A total of 34 patients with 36 clusters of suspicious calcifications (BI-RADS 4) were investigated with CEM before the scheduled VAB. We evaluated the presence or absence of enhancement, histologic diagnosis, and, in case of malignant lesions, their size and the expression of Ki-67. Results: In our case series, 15/36 (41.7%) lesions were malignant. In 7 cases, contrast enhancement was found at the site of calcifications. Data about size of lesions and immunohistochemical characterization were not available for all malignant cases. In 5 cases with CEM enhancement, all lesions were >5 mm and overexpressing Ki-67 (>20%); in 6 cases with no ...
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Background: Metastatic spreading is promoted by cancer cell seeding from the primary tumor into t... more Background: Metastatic spreading is promoted by cancer cell seeding from the primary tumor into the bloodstream. In patients with metastatic breast cancer (MBC), the clinical relevance of circulating tumor cell clusters (CTC-clusters) has been extensively reported, while their study in earlier stages is limited. Several methods, besides the FDA-cleared CellSearch®, limited to the detection of epithelial-enriched clusters, can be used for the detection of CTC-clusters. We hypothesize that resorting to marker-independent approaches can improve CTC-cluster detection. Methods: Blood samples collected from healthy donors and spiked-in with tumor mammospheres, or from BC patients, were processed for CTC-cluster detection with 3 technologies: CellSearch®, CellSieve™ filters, ScreenCell® filters. The number of CTC-clusters was compared among the technologies and analyzed in relation to patient characteristics and outcome. Results: In spiked-in samples, the 3 technologies showed similar capa...
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Cancer Letters
De novo or acquired resistance of cancer cells to currently available Human Epidermal Growth Fact... more De novo or acquired resistance of cancer cells to currently available Human Epidermal Growth Factor Receptor 2 (HER2) inhibitors represents a clinical challenge. Several resistance mechanisms have been identified in recent years, with lipid metabolism reprogramming, a well-established hallmark of cancer, representing the last frontier of preclinical and clinical research in this field. Fatty Acid Synthase (FASN), the key enzyme required for fatty acids (FAs) biosynthesis, is frequently overexpressed/activated in HER2-positive (HER2+) breast cancer (BC), and it crucially sustains HER2+ BC cell growth, proliferation and survival. After the synthesis of new, selective and well tolerated FASN inhibitors, clinical trials have been initiated to test if these compounds are able to re-sensitize cancer cells with acquired resistance to HER2 inhibition. More recently, the upregulation of FA uptake by cancer cells has emerged as a potentially new and targetable mechanism of resistance to anti-HER2 therapies in HER2+ BC, thus opening a new era in the field of targeting metabolic reprogramming in clinical setting. Here, we review the available preclinical and clinical evidence supporting the inhibition of FA biosynthesis and uptake in combination with anti-HER2 therapies in patients with HER2+ BC, and we discuss ongoing clinical trials that are investigating these combination approaches.
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Papers by Andrea Vingiani