Publications by authors named "Laura Cortesi"

133 Publications

ROLE OF RISK SCORING SYSTEMS IN PREDICTING LIFE EXPECTANCY AFTER CAROTID ENDARTERECTOMY IN ASYMPTOMATIC PATIENTS.

J Vasc Surg 2021 Oct 1. Epub 2021 Oct 1.

Laboratory of Research in Vascular Surgery, IRCCS Istituto Auxologico Italiano, Milan, Italy; Unit of Vascular Surgery, IRCCS Istituto Auxologico Italiano, Milan, Italy.

Objective: The aim of this study is to compare and to test the performance of all available risk scoring systems (RSSs) designed to predict long-term survival rate in asymptomatic candidate patients for carotid endarterectomy (CEA) for significant carotid artery stenosis.

Methods: Data on asymptomatic patients who underwent CEA in three high-volume centers were prospectively recorded. Through literature research using PRISMA recommendations, six RSSs were identified for the intent of the study. Primary endpoints were 3- and 5-year survival rate after CEA. All items used as variables to compose multiple RSSs were applied to every patient in the study population. The 3-year and 5-year mortality prediction rates for each score were assessed by sensitivity, specificity, predictive negative and positive value calculation, as well as univariable Cox proportional hazard models with the Harrell's C index.

Results: During the study period, 825 CEAs in 825 asymptomatic patients were analyzed. All items used in RSSs were available in the dataset, with some concerns regarding their definition and application among RSSs. The 3-year and 5-year survival rates of the study cohort were 94.5% and 90.3%, respectively. Among the six RSSs analyzed, no RSS demonstrated optimal results in terms of mortality rate prediction accuracy, although some scores had good diagnostic and risk of death precision.

Conclusion: RSSs, when used alone, fail to optimally detect postoperative life-expectancy in asymptomatic CEA patient candidates. Further prospective controlled studies are needed to compose and validate RSSs with better calibration to predict outcomes.
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http://dx.doi.org/10.1016/j.jvs.2021.08.099DOI Listing
October 2021

Transcriptome of Male Breast Cancer Matched with Germline Profiling Reveals Novel Molecular Subtypes with Possible Clinical Relevance.

Cancers (Basel) 2021 Sep 8;13(18). Epub 2021 Sep 8.

Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.

Male breast cancer (MBC) is a rare and understudied disease compared with female BC. About 15% of MBCs are associated with germline mutation in BC susceptibility genes, mainly and . Hereditary MBCs are likely to represent a subgroup of tumors with a peculiar phenotype. Here, we performed a whole transcriptome analysis of MBCs characterized for germline mutations in the most relevant BC susceptibility genes in order to identify molecular subtypes with clinical relevance. A series of 63 MBCs, including 16 6 , 2 , 1 , and 1 germline-mutated cases, was analyzed by RNA-sequencing. Differential expression and hierarchical clustering analyses were performed. Module signatures associated with central biological processes involved in breast cancer pathogenesis were also examined. Different transcriptome profiles for genes mainly involved in the cell cycle, DNA damage, and DNA repair pathways emerged between MBCs with and without germline mutations. Unsupervised clustering analysis revealed two distinct subgroups, one of which was characterized by a higher expression of immune response genes, high scores of gene-expression signatures suggestive of aggressive behavior, and worse overall survival. Our results suggest that transcriptome matched with germline profiling may be a valuable approach for the identification and characterization of MBC subtypes with possible relevance in the clinical setting.
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http://dx.doi.org/10.3390/cancers13184515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469418PMC
September 2021

Fulvestrant and trastuzumab in patients with luminal HER2-positive advanced breast cancer (ABC): an Italian real-world experience (HERMIONE 9).

Breast Cancer Res Treat 2021 Aug 27. Epub 2021 Aug 27.

Department of Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, via A. Manzoni 56 20089, Rozzano, Milano, Italy.

Purpose: The most appropriate therapy for HR + /HER2-positive (HER2 +) advanced breast cancer (ABC) is a matter of debate. Co-targeting of both receptors represents an attractive strategy to overcome the cross-talk between them.

Methods: The HERMIONE 9 is an observational retrospective multicentric study which aimed to describe the clinical outcome of patients with HR + /HER2 + ABC who received the combination of Fulvestrant (F) and Trastuzumab (T) as part of their routine treatment at 10 Italian Institutions.

Results: Eighty-seven patients were included. Median age was 63 (range, 35-87) years. The median number of previous treatments was 3 (range, 0-10) and F and T were administered as ≥ 3rd line in 67 patients. Among the 86 evaluable patients, 6 (6.9%) achieved CR, 18 (20.7%) PR, and 44 (50.6%) had SD ≥ 24 weeks with an overall CBR of 78.2%. At a median follow-up of 33.6 months, mPFS of the entire cohort was 12.9 months (range, 2.47-128.67). No difference was observed in mPFS between patients treated after progression or as maintenance therapy (mPFS 12.9 and 13.9 months in 64 and 23 patients, respectively), neither considering the number of previous treatment lines (≤ 3 or < 3).

Conclusion: The combination of F and T was active in this cohort at poor prognosis and deserves further investigations possibly in combination with pertuzumab in patients with high ER expression.
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http://dx.doi.org/10.1007/s10549-021-06371-9DOI Listing
August 2021

The tumor-agnostic treatment for patients with solid tumors: a position paper on behalf of the AIOM- SIAPEC/IAP-SIBioC-SIF Italian Scientific Societies.

Crit Rev Oncol Hematol 2021 Sep 8;165:103436. Epub 2021 Aug 8.

Department of Oncology, Humanitas Gavazzeni, Bergamo, Italy.

The personalized medicine is in a rapidly evolving scenario. The identification of actionable mutations is revolutionizing the therapeutic landscape of tumors. The morphological and histological tumor features are enriched by the extensive genomic profiling, and the first tumor-agnostic drugs have been approved regardless of tumor histology, guided by predictive and druggable genetic alterations. This new paradigm of "mutational oncology", presents a great potential to change the oncologic therapeutic scenario, but also some critical aspects need to be underlined. A process governance is mandatory to ensure the genomic testing accuracy and homogeneity, the economic sustainability, and the regulatory issues, ultimately granting the possibility of translating this model in the "real world". In this position paper, based on experts' opinion, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies revised the new agnostic biomarkers, the diagnostic technologies available, the current availability of agnostic drugs and their present indication.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103436DOI Listing
September 2021

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.

J Natl Cancer Inst 2021 Jul 28. Epub 2021 Jul 28.

Department of Molecular Medicine, University La Sapienza, Rome, Italy.

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.

Methods: 483 BRCA1 and 1,318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were three versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen-receptor (ER) negative (PRSER-) or ER-positive (PRSER+) breast cancer risk.

Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07-1.83) for BRCA1 and 1.33 (95% CI = 1.16-1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for both BRCA1 (OR = 1.73, 95% CI = 1.28-2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34-1.91) carriers. The estimated breast cancer ORs were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.

Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and to inform clinical management.
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http://dx.doi.org/10.1093/jnci/djab147DOI Listing
July 2021

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions.

Int J Mol Sci 2021 Jul 19;22(14). Epub 2021 Jul 19.

SOD Molecular Genetics, University Hospital of Pisa, 56126 Pisa, Italy.

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (, , , , , , , , , , , ) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, for germline mutation in genes. The analysis was extended to 5'UTR and 3'UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients. The screening was performed through NGS target resequencing on the Illumina platform MiSeq. 8.7% of the patients analyzed is carriers of class 5/4 coding variants in the (3.6%), (1.6%), (1.8%), (0.7%), (0.4%), (0.4%), and (0.2%) genes, while variants of uncertain pathological significance (VUSs)/class 3 were identified in 9.1% of the samples. In intron-exon junctions and in regulatory regions, variants were detected respectively in 5.1% and in 32.5% of the cases analyzed. The average age of disease onset of 44.4 in non-coding variant carriers is absolutely similar to the average age of disease onset in coding variant carriers for each proband's group with the same cancer type. Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a 3'UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.
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http://dx.doi.org/10.3390/ijms22147693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305371PMC
July 2021

Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study.

J Pers Med 2021 Jun 20;11(6). Epub 2021 Jun 20.

SSc Unit, Rheumatology Unit, Azienda Ospedaliero-Universitaria di Modena, 41124 Modena, Italy.

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.
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http://dx.doi.org/10.3390/jpm11060580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234103PMC
June 2021

Automated capture-based NGS workflow: one thousand patients experience in a clinical routine framework.

Diagnosis (Berl) 2021 Jun 16. Epub 2021 Jun 16.

Department of Laboratory Medicine and Pathology, Diagnostic Hematology and Clinical Genomics Unit, Modena University Hospital, Modena, Italy.

Objectives: The Next Generation Sequencing (NGS) based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization.

Methods: We implemented the automation of the CE-IVD SOPHiA Hereditary Cancer Solution™ (HCS) libraries preparation workflow by SOPHiA GENETICS on the Hamilton's STARlet platform. We present the comparison of results between this automated approach, used for more than 1,000 DNA patients' samples, and the performances of the manual protocol evaluated by SOPHiA GENETICS onto 240 samples summarized in their HCS evaluation study.

Results: We demonstrate that this automated workflow achieved the same expected goals of manual setup in terms of coverages and reads uniformity, with extremely lower standard deviations among samples considering the sequencing reads mapped onto the regions of interest.

Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory's walk-away scenario.
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http://dx.doi.org/10.1515/dx-2021-0051DOI Listing
June 2021

Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Center for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.

The NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and reviewed the literature. Three patients (2.6%) carried potentially relevant variants: two, apparently unrelated, carried the frameshift variant c.156_157delTT and another one the c.628G>T variant. The latter was subsequently found in 4/1390 (0.3%) BC cases and 8/1580 (0.5%) controls in an independent sample, which, together with in silico predictions, provided evidence against its pathogenicity. Conversely, the rare c.156_157delTT variant was absent in the case-control set; moreover, a 50% reduction of NBN expression was demonstrated in one carrier. However, in one family it failed to co-segregate with BC, while the other carrier was found to harbor also a probably pathogenic TP53 variant that may explain her phenotype. Therefore, the c.156_157delTT, although functionally deleterious, was not supported as a cancer-predisposing defect. Pathogenic/likely pathogenic NBN variants were detected by multigene panels in 31/12314 (0.25%) patients included in 15 studies. The risk of misinterpretation of such findings is substantial and supports the exclusion of NBN from multigene panels.
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http://dx.doi.org/10.3390/ijms22115832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198239PMC
May 2021

BRCA mutation carriers' perceptions on postmenopausal hormone therapy: An Italian study.

Psychooncology 2021 10 28;30(10):1711-1719. Epub 2021 May 28.

Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Objective: To evaluate the actual perceptions of postmenopausal hormone therapy (HT) in BRCA mutation carriers (BRCAmc) in comparison with women from the general population.

Methods: Questionnaire-based study of 83 BRCAmc and a control group of 89 women without a genetic mutation. Perceptions were evaluated by specific questions and Likert scales (-5-+5).

Results: Present and past users of HT were more frequent in the control group (p = 0.01), with a longer time of use (p = 0.03). The preferred route of administration of HT was 'oral' (54.6%). The most frequently reported adverse effect of HT was venous thrombosis (0.8), while a protective effect on bone health was reported. No noticeable beneficial effects of HT have been recognised for hot flushes (0.2) and vaginal dryness (0.1). The most frequently perceived beneficial and adverse effects of HT were not significantly different between BRCA mutation carriers and controls. The greatest oncological fear was breast cancer (1.0). The protective role of HT on colorectal cancer was not known (0.1). These oncological impacts were mostly overestimated in BRCAmc, however this was not significant. Few BRCAmc would think of taking HT after risk-reducing surgeries.

Conclusions: Knowledge of the effects of HT on BRCAmc is relatively poor and they are likely to overstate its negative effects and underestimate its health benefits; however, this is not significant in comparison to the general population. More and better information should be given to BRCAmc to allow them to make informed decisions about the use of HT, especially before undergoing risk-reducing surgeries.
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http://dx.doi.org/10.1002/pon.5714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518789PMC
October 2021

Clinicopathologic Profile of Breast Cancer in Germline ATM and CHEK2 Mutation Carriers.

Genes (Basel) 2021 04 21;12(5). Epub 2021 Apr 21.

Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy.

The most common breast cancer (BC) susceptibility genes beyond are and . For the purpose of exploring the clinicopathologic characteristics of BC developed by or mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen and 17 mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in (26.3%) and mutation carriers (41.2%). While 64.3% of tumors were luminal A-like, 56.2% of tumors were luminal B-like/HER2-negative. Moreover, 21.4% of -related invasive tumors showed a lobular histotype. About a quarter of all -related BCs and a third of BCs were in situ carcinomas and more than half of and -related BCs were diagnosed at stage I-II. Finally, 63.2% of mutation carriers and 64.7% of mutation carriers presented a positive BC family history. The biological and clinical characteristics of and -related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with and mutation carriers at the first diagnosis of BC.
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http://dx.doi.org/10.3390/genes12050616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143279PMC
April 2021

The Prognostic and Predictive Role of Somatic Mutations in Ovarian Cancer: Results from a Multicenter Cohort Study.

Diagnostics (Basel) 2021 Mar 21;11(3). Epub 2021 Mar 21.

Department of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41124 Modena, Italy.

Previous research involving epithelial ovarian cancer patients showed that, compared to germline (gBRCA) mutations, somatic (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.
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http://dx.doi.org/10.3390/diagnostics11030565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003908PMC
March 2021

Germline Mutations in Other Homologous Recombination Repair-Related Genes Than : Predictive or Prognostic Factors?

J Pers Med 2021 Mar 28;11(4). Epub 2021 Mar 28.

Genetic Oncology Unit, Department of Oncology and Haematology, University Hospital of Modena, 41125 Modena, Italy.

The homologous recombination repair (HRR) pathway repairs double-strand DNA breaks, mostly by BRCA1 and BRCA2, although other proteins such as ATM, CHEK2, and PALB2 are also involved. germline mutations are targeted by PARP inhibitors. The aim of this commentary is to explore whether germline mutations in HRR-related genes other than have to be considered as prognostic factors or predictive to therapies by discussing the results of two articles published in December 2020. The TBCRC 048 trial published by Tung et al. showed an impressive objective response rate to olaparib in metastatic breast cancer patients with germline mutation compared to germline and mutation carriers. Additionally, Yadav et al. observed a significantly longer overall survival in pancreatic adenocarcinoma patients with germline HRR mutations compared to non-carriers. In our opinion, assuming that is a high-penetrant gene with a key role in the HRR system, mutations are predictive factors for response to treatment. Moreover, germline mutations in the gene provide a better outcome in pancreatic adenocarcinoma, being more often associated to wild-type . In conclusion, sequencing of HRR-related genes other than should be routinely offered as part of a biological characterization of pancreatic and breast cancers.
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http://dx.doi.org/10.3390/jpm11040245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066561PMC
March 2021

mutation rate and characteristics of prostate tumor in breast and ovarian cancer families: analysis of 6,591 Italian pedigrees.

Cancer Biol Med 2021 Mar 12. Epub 2021 Mar 12.

Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena 41124, Italy.

Objective: As prostate cancer (PrC) shows a mutation rate as high as 30%, it becomes crucial to find the optimal selection criteria for genetic testing. The primary objective of this study was to evaluate the mutation rate in families with PrC associated with breast and/or ovarian cancers; secondary aims were to compare the characteristics of families and BRCA-related PrC outcome among and carriers.

Methods: Following the Modena criteria for the test, we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score ≥7 PrCs, by testing breast or ovarian cases and inferring the mutation in the prostate cases. The characteristics of families and BRCA-related PrC outcomes were measured using the chi-square (χ) test and Kaplan-Meier methods, respectively.

Results: Among 6,591 families, 580 (8.8%) with a Gleason score ≥ 7 PrCs were identified, of which 332 (57.2%) met the Modena selection criteria for BRCA testing. Overall, 215 breast or ovarian cancer probands (64.8%) were tested, of which 41 resulted positive for and one for genes (19.5%). No statistically significant differences were found in BRCA-related PrC prognosis and in the characteristics of families among BRCA1, BRCA2 and non-tested patients. Ten of 23 (44%) mutations in the gene fell in the prostate cancer cluster region (PCCR) at the 3´ terminal of the 7914 codon.

Conclusions: It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and PrC. A trend toward a worse prognosis has been found in carriers.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185862PMC
March 2021

An Overview of PARP Inhibitors for the Treatment of Breast Cancer.

Target Oncol 2021 05 12;16(3):255-282. Epub 2021 Mar 12.

Sana Klinikum Offenbach, Department of Obstetrics and Gynecology and Breast Cancer Center, Starkenburgring 66, 63069, Offenbach, Germany.

Loss-of-function mutations in BRCA1 and BRCA2 are detected in at least 5% of unselected patients with breast cancer (BC). These BC susceptibility genes encode proteins critical for DNA homologous recombination repair (HRR). This review provides an update on oral poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of BC. Olaparib and talazoparib are PARP inhibitors approved as monotherapies for deleterious/suspected deleterious germline BRCA-mutated, HER2-negative BC. Olaparib is approved in the USA for metastatic BC and in Europe for locally advanced/metastatic BC. Talazoparib is approved for locally advanced/metastatic BC in the USA and Europe. In phase 3 trials, olaparib and talazoparib monotherapies demonstrated significant progression-free survival benefits compared with chemotherapy. Common toxicities were effectively managed by supportive treatment and dose interruptions/reductions. Veliparib combined with platinum-based chemotherapy has also shown promise for locally advanced/metastatic BC in a phase 3 trial. Differences in efficacy and safety across PARP inhibitors (olaparib, talazoparib, veliparib, niraparib, rucaparib) may relate to differences in potency of PARP trapping on DNA and cytotoxic specificity. PARP inhibitors are being investigated in early BC, in novel combinations, and in patients without germline BRCA mutations, including those with somatic BRCA mutations and other HRR gene mutations. Ongoing phase 2/3 studies include PARP inhibitors combined with immune checkpoint inhibitors for the treatment of triple-negative BC. Wider access to testing for BRCA and other mutations, and to genetic counseling, are required to identify patients who could benefit from PARP inhibitor therapy. The advent of PARP inhibitors has potential benefits for BC treatment beyond the locally advanced/metastatic setting.
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http://dx.doi.org/10.1007/s11523-021-00796-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105250PMC
May 2021

Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer.

Ther Adv Med Oncol 2021 9;13:1758835920985632. Epub 2021 Feb 9.

Department of Clinical and Experimental Oncology and Hematology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Background: The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity.

Patients And Methods: This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m intravenously (i.v.) on day 1, docetaxel, 30 mg/m i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle.

Results: Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5-53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06-1.30,  = 0.11). Toxicity included grade 3-4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1-2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1-2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase.

Conclusions: The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens.
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http://dx.doi.org/10.1177/1758835920985632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876584PMC
February 2021

Effect Modifiers of Low-Dose Tamoxifen in a Randomized Trial in Breast Noninvasive Disease.

Clin Cancer Res 2021 07 19;27(13):3576-3583. Epub 2021 Feb 19.

IEO, European Institute of Oncology IRCCS, Milan, Italy.

Purpose: Low-dose tamoxifen halved recurrence after surgery in a phase III trial in breast noninvasive disease without increasing adverse events. We explored the effect of low-dose tamoxifen in clinically relevant subgroups, including menopausal status, estradiol levels, smoking, body mass index, and proliferation of baseline lesion.

Patients And Methods: Incidence of invasive breast cancer or ductal carcinoma was the primary endpoint. HRs and interaction terms were estimated using Cox models.

Results: A favorable HR and 95% confidence interval (CI) could be demonstrated for postmenopausal status (HR = 0.30; 95% CI, 0.11-0.82 vs. HR = 0.73; 95% CI, 0.30-1.76 in premenopausal women; = 0.13), women with estradiol less than 15.8 pg/mL, presence of menopausal symptoms at baseline, and never smoking ( = 0.07), although the interaction value was >0.05 for all characteristics. Efficacy was similar in all body mass index categories. Tumors with Ki-67 above the median level of 10% had a greater benefit (HR = 0.27; 95% CI, 0.09-0.81) than those with Ki-67 ≤10% (HR = 1.58; 95% CI, 0.45-5.60; = 0.04).

Conclusions: The efficacy of low-dose tamoxifen seems to be greater in postmenopausal women and in women with lower estradiol levels. Benefits appear to be larger also in women with menopausal symptoms, never smokers, and tumors with Ki-67 >10%. Our results by menopausal status provide important insight into low-dose tamoxifen personalized treatment, although caution is necessary given their exploratory nature. Observation of an improved response in tumors with Ki-67 >10% is consistent but the use of the marker in this setting is investigational..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4213DOI Listing
July 2021

Satisfaction with prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers is very high and little dependent on the participants' characteristics at surgery: a prospective study.

Menopause 2021 02 1;28(3):263-270. Epub 2021 Feb 1.

Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Azienda Ospedaliero Universitaria Policlinico, Modena, Italy.

Objective: BRCA carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO). Possible adverse health impacts of RRSO, particularly when done before natural menopause, can reduce the long-term satisfaction with this risk-reducing strategy. The aim of this study was to prospectively evaluate the level of satisfaction of women undergoing RRSO, also in relation to some specific characteristics at RRSO.

Methods: A prospective cohort study was performed in the Modena Family Cancer Clinic of the University Hospital of Modena (Italy). All BRCA1/2 confirmed mutation carriers who decided to undergo RRSO were recruited between 2016 and 2019.

Results: Fifty-five women (29 BRCA1 and 26 BRCA2) (mean age: 50.4 ± 7.7 years [range 35-79]) were included with a mean follow-up after RRSO of 660.9 days (1.8 years) (range 35-1,688 days) (median: 549 days). No intraepithelial (Serous Tubal Intraepithelial Carcinoma)/invasive cancers were found (0%) at RRSO. No vasomotor symptoms at 1 month after surgery were reported by 11/22 (50%) premenopausal women at RRSO. All women (100%) with new "RRSO-caused" vasomotor symptoms with no previous breast cancer initiated postmenopausal hormone therapy. At the final follow-up the satisfaction rate (0-100 visual analog scale points) of the participants was 96.4 ± 8.6 points (range 62-100). To the question "Would you undergo RRSO again if it was proposed today? (0-100 visual analog scale points)" the answer was 99.4 ± 3.2 points (range 79-100). These scores were in general very high and did not change in the different groups according to pre/postmenopausal status at RRSO, cancer survivors versus healthy women at RRSO, BRCA status, hormone therapy users/nonusers after RRSO, "RRSO-caused" symptoms versus not RRSO-caused (P > 0.05).

Conclusions: Findings from this prospective study suggest that satisfaction with RRSO is very high and little dependent on the participants' characteristics at surgery. Women at high risk for ovarian cancer are very satisfied with their choice of risk-reduction strategy.
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http://dx.doi.org/10.1097/GME.0000000000001737DOI Listing
February 2021

Characterization of New Deletion Associated with Hereditary Breast Cancer.

Genes (Basel) 2021 01 21;12(2). Epub 2021 Jan 21.

Centre for Regenerative Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Next-generation sequencing (NGS)-based cancer risk screening with multigene panels has become the most successful method for programming cancer prevention strategies. germ-line heterozygosity has been described to increase tumor susceptibility. In particular, families carrying heterozygous germ-line variants of gene have a 5- to 9-fold risk of developing breast cancer. Recent studies identified as the second most mutated gene after in BRCA-negative patients. Nowadays, more than 170 missense variants and several truncating mutations have been identified in gene. Here, we present the molecular characterization of a new deletion, identified thanks to the CNV algorithm implemented in the NGS analysis pipeline. An automated workflow implementing the SOPHiA Genetics' Hereditary Cancer Solution (HCS) protocol was used to generate NGS libraries that were sequenced on Illumina MiSeq Platform. NGS data analysis allowed us to identify a new inactivating deletion of exons 19-27 of gene. The deletion was characterized both at the DNA and RNA level.
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http://dx.doi.org/10.3390/genes12020136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911716PMC
January 2021

The multifaceted spectrum of liver cirrhosis in older hospitalised patients: analysis of the REPOSI registry.

Age Ageing 2021 02;50(2):498-504

Unit of Geriatrics, University Campus Bio-Medico, Rome, Italy.

Background: Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce.

Objectives: To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties.

Methods: A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed.

Results: LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT.

Conclusions: LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features.
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http://dx.doi.org/10.1093/ageing/afaa150DOI Listing
February 2021

Pharmacist-driven medication recognition/ reconciliation in older medical patients.

Eur J Intern Med 2021 Jan 7;83:39-44. Epub 2020 Aug 7.

Scientific Direction, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: In older medical patients polypharmacy is often associated with poor prescription appropriateness and harmful drug-drug interactions. An effort that jointly involved hospital pharmacists and clinicians attending multimorbid older patients acutely admitted to medical wards was implemented for medication recognition and reconciliation aided by the use of a computerized support system.

Methods: Six internal medicine wards enrolled consecutively 90 acutely admitted multimorbid patients aged 75 years or more taking 5 or more different drugs. Two hospital pharmacists carried out the recognition of medications taken at hospital ward admission, and interacted with the clinicians in a process of drug reconciliation, using also the computerized support system to evaluate drug related problems, prescription inappropriateness or drug-drug interactions. The process was repeated at hospital discharge.

Results: Among a total number of 911 drugs prescribed to 90 older medical patients at ward admission, the pharmacists identified during their recognition/reconciliation 455 drug-related problems, mainly due to prescription of medications inappropriate for older multimorbid patients and clinically harmful drug-drug interactions. When these drug-related problems were identified by the pharmacist, the attending clinicians accepted and implemented the suggestions for changes for approximately two thirds of the discrepancies, thereby leading to deprescribing the implicated drugs or at least to their closer monitoring.

Conclusions: This interventional prospective study based upon the integrated expertise of hospital pharmacists and clinicians confirms that drug-related problems are frequent in multimorbid older patients acutely admitted to hospital medical wards, and demonstrates afresh the feasibility and mutual acceptance of a trajectory of recognition/reconciliation based upon an integrated collaboration between hospital pharmacists and ward clinicians in the process of medication optimization.
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http://dx.doi.org/10.1016/j.ejim.2020.07.011DOI Listing
January 2021

Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA.

J Oncol 2020 14;2020:6384190. Epub 2020 Jul 14.

Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.

BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndromes are among the best-known and most extensively studied hereditary cancer syndromes. Nevertheless, many patients who proved negative at BRCA genetic testing bring pathogenic mutations in other suppressor genes and oncogenes associated with hereditary breast and/or ovarian cancers. These genes include in Li-Fraumeni syndrome, in Cowden syndrome, mismatch repair () genes in Lynch syndrome, in diffuse gastric cancer syndrome, in Peutz-Jeghers syndrome, and in neurofibromatosis type 1 syndrome. To these, several other genes can be added that act jointly with and in the double-strand break repair system, such as , , , , , and . Management of primary and secondary cancer prevention in these hereditary cancer syndromes is crucial. In particular, secondary prevention by screening aims to discover precancerous lesions or cancers at their initial stages because early detection could allow for effective treatment and a full recovery. The present review aims to summarize the available literature and suggest proper screening strategies for hereditary breast and/or ovarian cancer syndromes other than BRCA.
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http://dx.doi.org/10.1155/2020/6384190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376433PMC
July 2020

Pregnancy After Breast Cancer in Patients With Germline Mutations.

J Clin Oncol 2020 09 16;38(26):3012-3023. Epub 2020 Jul 16.

Department of Medical Oncology, Institut Jules Bordet and Université Libre de, Brussels, Belgium.

Purpose: Young women with germline mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline mutations.

Patients And Methods: This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors.

Results: Of 1,252 patients with germline mutations (, 811 patients; , 430 patients; , 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; = .66) were observed between the pregnancy and nonpregnancy cohorts.

Conclusion: Pregnancy after breast cancer in patients with germline mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with -mutated breast cancer interested in future fertility.
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http://dx.doi.org/10.1200/JCO.19.02399DOI Listing
September 2020

Postmenopausal hormone therapy in BRCA gene mutation carriers: to whom and which?

Expert Opin Drug Saf 2020 Aug 10;19(8):1025-1030. Epub 2020 Jul 10.

Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico , Modena, Italy.

Introduction: Risk-reducing-salpingo-oophorectomy (RRSO) inevitably leads BRCA mutation carriers to premature menopause.

Areas Covered: To evaluate the existing evidence for use of postmenopausal hormone therapy (HT) in BRCAmc, after RRSO or menopause occurring naturally, for both breast cancer (BC) survivors and those without BC.

Expert Opinion: All BC survivors are excluded from any HT treatment: in other BRCAmc, before 51 years of age the benefits of HT overcome the risks after RRSO and/or premature ovarian insufficiency (POF). After 51 years of age, it is important to treat only women with important vasomotor symptoms, after the failure of alternative therapies. Estrogens-only therapy plays a key role in hysterectomized women (HW). In the case of an intact uterus (UW), associations with the lowest dose of progestins/natural progesterone derivatives have to be preferred, as progestins has been shown to play an important role in BC transformation, especially in BRCA1mc. No studies have been performed in BRCAmc with regard to 'progestin-free' HT, in particular the old tibolone (both in HW and UW) and the new tissue-selective estrogen complex (in UW). However, preliminary data obtained from the general population are reassuring about the use of these 'progestin-free' preparations and BC safety.
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http://dx.doi.org/10.1080/14740338.2020.1791818DOI Listing
August 2020

Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

JAMA Oncol 2020 08;6(8):1218-1230

Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population.

Objective: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers.

Design, Setting, And Participants: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected.

Main Outcomes And Measures: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview.

Results: Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P < .001), as well as developing 2 (OR, 7.97; 95% CI, 5.47-11.60; P < .001) and 3 (OR, 19.60; 95% CI, 4.64-82.89; P < .001) primary tumors. A higher frequency of breast (OR, 5.47; 95% CI, 4.06-7.37; P < .001) and prostate (OR, 1.39; 95% CI, 1.09-1.78; P = .008) cancers was associated with a higher probability of being a BRCA2 PV carrier. Among cancers other than breast and prostate, pancreatic cancer was associated with a higher probability (OR, 3.00; 95% CI, 1.55-5.81; P = .001) and colorectal cancer with a lower probability (OR, 0.47; 95% CI, 0.29-0.78; P = .003) of being a BRCA2 PV carrier.

Conclusions And Relevance: Significant differences in the cancer spectrum were observed in male BRCA2, compared with BRCA1, PV carriers. These data may inform future recommendations for surveillance of BRCA1/2-associated cancers and guide future prospective studies for estimating cancer risks in men with BRCA1/2 PVs.
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http://dx.doi.org/10.1001/jamaoncol.2020.2134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333177PMC
August 2020

Lifestyle Intervention on Body Weight and Physical Activity in Patients with Breast Cancer can reduce the Risk of Death in Obese Women: The EMILI Study.

Cancers (Basel) 2020 Jun 27;12(7). Epub 2020 Jun 27.

Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, 41124 Modena, Italy.

Background obesity and sedentary lifestyle have been shown to negatively affect survival in breast cancer (BC). The purpose of this study was to test the efficacy of a lifestyle intervention on body mass index (BMI) and physical activity (PA) levels among BC survivors in Modena, Italy, in order to show an outcome improvement in obese and overweight patients.

Methods: This study is a single-arm experimental design, conducted between November 2009 and May 2016 on 430 women affected by BC. Weight, BMI, and PA were assessed at baseline, at 12 months, and at the end of the study. Survival curves were estimated among normal, overweight, and obese patients.

Results: Mean BMI decreased from baseline to the end of the study was equal to 2.9% ( = 0.065) in overweight patients and 3.3% in obese patients ( = 0.048). Mean PA increase from baseline to the end of the study was equal to 125% ( < 0.001) in normal patients, 200% ( < 0.001) in overweight patients and 100% ( < 0.001) in obese patients. After 70 months of follow-up, the 5-year overall survival (OS) rate was 96%, 96%, and 93%, respectively in normal, obese, and overweight patients. Overweight patients had significantly worse OS than normal ones (HR = 3.69, 95%CI = 1.82-4.53 = 0.027) whereas no statistically significant differences were seen between obese and normal patients (HR 2.45, 95%CI = 0.68-8.78, = 0.169).

Conclusions: A lifestyle intervention can lead to clinically meaningful weight loss and increase PA in patients with BC. These results could contribute to improving the OS in obese patients compared to overweight ones.
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http://dx.doi.org/10.3390/cancers12071709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407899PMC
June 2020

Breast cancer screening of mutation carriers in the era of COVID-19 pandemic.

Int J Cancer 2020 12 1;147(12):3574-3575. Epub 2020 Jul 1.

Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

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http://dx.doi.org/10.1002/ijc.33160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323406PMC
December 2020

Male bilateral risk-reducing mastectomy: Report of a case.

Breast J 2020 10 9;26(10):2135-2136. Epub 2020 Jun 9.

Division of Breast Surgical Oncology, Department of Medical and Surgical, Maternal-Infantile and Adult Sciences, University Hospital of Modena, Modena, Italy.

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http://dx.doi.org/10.1111/tbj.13928DOI Listing
October 2020

The reduction of CA 125 serum levels in BRCA 1/2 mutation carriers after risk-reducing salpingo-oophorectomy is only partially associated with surgery: a prospective cohort, other biomarker controlled, study.

Eur J Cancer Prev 2020 07;29(4):350-356

Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena.

Objectives: A significant reduction in CA 125 postoperative serum levels was observed after risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers. In contrast to previous studies, where control groups were absent, we conducted a prospective study including also a screening only group (RSSO refusal) and a group having previously undergone RRSO.

Methods: Consecutive BRCA1 and BRCA2 mutation carriers, not hysterectomised, >35 years old and with completed childbearing, were recruited. Some women had previously undergone RRSO (previous RRSO group). The others, who had either chosen RRSO (actual RRSO group) or screening only (screening only group), were enrolled (patient-preference trial). A prospective evaluation (basal and 6-month) of CA 125 and CEA (control biomarker) was performed.

Results: The study consisted of 116 women, 44.8% BRCA1 and 55.2% BRCA2 mutation carriers (n = 25 in the previous RRSO group, n = 29 in the actual RRSO group, n = 62 in the screening only group). For all subjects, we observed a 6-month decrease in CA 125 (-7.8%, P = 0.003), which was significantly linked only to endometriosis history (odds ratio 1.4; 95% confidence interval 1.1-1.8; P = 0.002). Between different groups, we recorded a non-significantly different decrease in CA 125. CEA showed a 6 months significant increase (+15.4%, P < 0.0001), which was similar between groups.

Conclusion: The decrease in CA 125 in BRCA mutation carriers after RRSO was only partially associated with surgery, depending also on a physiological decline: this is extremely important in their longitudinal monitoring for the prevention of ovarian cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000606DOI Listing
July 2020

Inappropriate prescribing in intermediate care facilities.

Aging Clin Exp Res 2021 Apr 28;33(4):1085-1088. Epub 2020 May 28.

ASP Pio Albergo Trivulzio, Milan, Italy.

Inappropriate prescribing for older people is a global healthcare problem. This study aimed to determine the prevalence of older patients receiving potentially inappropriate medications (PIMs) at admission and discharge at the intermediate care facility of ASP Pio Albergo Trivulzio. We consecutively enrolled 100 patients aged ≥ 65 from December 2017 to May 2018 and evaluated PIMs with the 2015 version of the Beers criteria. We found a significant reduction in the prescription of drugs to avoid and proton pump inhibitors (PPIs), while patients with at least one psychotropic drug to avoid or to use with caution significantly increased. The inappropriate prescription of PPIs was mainly associated with the use of heparin. Optimizing PPI and psychotropic drug prescriptions should be considered for deprescribing inappropriate polypharmacy in intermediate care facilities.
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http://dx.doi.org/10.1007/s40520-020-01602-3DOI Listing
April 2021
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