Homologous recombination deficiency in pancreatic neuroendocrine tumors.

Pancreatic Neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms whose tumor biology is still little known. Thanks to next-generation sequencing, pathogenic mutations in base-excision-repair gene and homologous recombination genes and seem to have a role in the development of pNETs. We assumed that Homologous Recombination Deficiency (HRD) could be a critical pathogenetic mechanism for pNETs.

Chemoprevention strategies in hereditary breast and ovarian cancer syndromes.

Hereditary breast and/or ovarian cancer syndromes are inherited disorders in which there is an increased risk of developing breast and/or ovarian cancer in the lifetime, usually at a younger age compared to the general population. Cancer prevention in these syndromes includes prophylactic surgeries, personalized surveillance programs and chemopreventive strategies. Chemoprevention exploits the use of certain drugs or other substances to help lower the risk of developing cancer.

Did Michelangelo paint a young adult woman with breast cancer in "The Flood" (Sistine Chapel, Rome)?

The Flood is the first pictorial scene that Michelangelo Buonarroti painted on the ceiling of the Sistine Chapel in the Vatican. On the right side of the fresco a woman with abnormal breast morphology is presented and the nature of her disease is considered using the Guidelines for Iconodiagnosis. A team of experts covering art history, art expertise, medicine, genetics, and pathology undertook the process and concluded that the pathology shown is probably breast cancer, most likely linked to the symbolic significance of an inevitable death as expressed in the Book of Genesis.

Follow-up of early breast cancer in a public health system: A 2024 AIGOM consensus project.

Breast cancer stands as the most frequently diagnosed cancer and the primary cause of cancer-related mortality among women worldwide, including Italy. With the increasing number of survivors, many are enrolled in regular follow-up programs. However, adherence to recommendations from scientific societies (such as ASCO, ESMO, AIOM) for breast cancer follow-up management varies in daily clinical practice across different cancer centers, potentially resulting in unequal management and escalating costs.

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review.

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs.

Evaluation of an Italian Population-Based Programme for Risk Assessment and Genetic Counselling and Testing for BRCA1/2-Related Hereditary Breast and Ovarian Cancer after 10 Years of Operation: An Observational Study Protocol.

Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes.

Atypical cancer risk profile in carriers of Italian founder BRCA1 variant p.His1673del: Implications for classification and clinical management.

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy.

Can contralateral prophylactic mastectomy and oophorectomy increase survival in BRCA-related breast cancer? Results from the Italian MUTina study.

Introduction: In the Emilia-Romagna region of Italy, a unique Hub and Spoke model was adopted to recognize BRCA-related breast cancer (BC) patients. Characteristics and outcomes of tumors identified by this model will be presented.

Methods: This multicenter retrospective cohort study involved patients diagnosed with BRCA-related BC identified in the Emilia-Romagna region between January 2000 and December 2013.

BRCA Testing for Patients Treated in Italy: A National Survey of Breast Centers Associated with Senonetwork.

Background: Breast units (BUs) provide breast cancer (BC) care, including prevention, treatment, and genetic assessment. Genetic research has highlighted BRCA1/2 mutations as key hereditary BC risk factors. BRCA testing is crucial for personalized treatment and prevention strategies.

DCE-MRI Radiomic analysis in triple negative ductal invasive breast cancer. Comparison between BRCA and not BRCA mutated patients: Preliminary results.

Objective: The research aimed to determine whether and which radiomic features from breast dynamic contrast enhanced (DCE) MRI could predict the presence of BRCA1 mutation in patients with triple-negative breast cancer (TNBC).

Material And Methods: This retrospective study included consecutive patients histologically diagnosed with TNBC who underwent breast DCE-MRI in 2010-2021. Baseline DCE-MRIs were retrospectively reviewed; percentage maps of wash-in and wash-out were computed and breast lesions were manually segmented, drawing a 5 mm-Region of Interest (ROI) inside the tumor and another 5 mm-ROI inside the contralateral healthy gland.

Germline pathogenic variants of cancer predisposition genes in a multicentre Italian cohort of pancreatic cancer patients.

Background And Aim: Germline BRCA1-2 test is routinely recommended in Pancreatic Cancer (PC) patients, due to its clinical-epidemiological relevance. Data on the prevalence of germline pathogenic variants (gPV) in other cancer predisposition and DNA Damage Repair (DDR) system-related genes in unselected PC cases are sparce in Italy. We assessed this prevalence in a multicentre cohort, to derive recommendations for PC patients.

Navigating practical challenges in immunotherapy for metastatic triple negative breast cancer.

Immunotherapy has revolutionized cancer therapy and now represents a standard of care for many tumor types, including triple-negative breast cancer. Despite the positive results that have led to the approval of immunotherapy in both early- and advanced-stage triple-negative breast cancer, pivotal clinical trials cannot address the myriad questions arising in everyday clinical practice, often falling short in delivering all the information that clinicians require. In this manuscript, we aim to address some of these practical questions, with the purpose of providing clinicians with a guide for optimizing the use of immune checkpoint inhibitors in the management of breast cancer patients and identifying opportunities for future research to clarify unresolved questions.

Fenretinide in Young Women at Genetic or Familial Risk of Breast Cancer: A Placebo-Controlled Biomarker Trial.

Unlabelled: Fenretinide, a retinoid with a low-toxicity profile that accumulates in the breast, has been shown to prevent second breast cancer in young women. Fenretinide exhibits apoptotic and antiinvasive properties and it improves insulin sensitivity in overweight premenopausal women with insulin resistance. This study aimed to further characterize its role in cancer prevention by measuring circulating biomarkers related to insulin sensitivity and breast cancer risk.

Development and validation of the Medical Attitudes Towards Deprescribing Questionnaire.

Polypharmacy and inappropriate prescriptions in the elderly are widely discussed themes in scientific literature. Although more and more studies showed the safety and feasibility of deprescribing strategies, these are not implemented in clinical practice. In order to measure the attitudes of Italian doctors towards deprescribing and address their awareness, experiences, difficulties in applying these strategies and potential suggestions, we aimed to develop and validate a questionnaire, the Medical Attitudes Towards Deprescribing Questionnaire (MATD-Q).

Spatial Distribution of Immune Cells Drives Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Neoadjuvant chemotherapy (NAC) alone or combined with target therapies represents the standard of care for localized triple-negative breast cancer (TNBC). However, only a fraction of patients have a response, necessitating better understanding of the complex elements in the TNBC ecosystem that establish continuous and multidimensional interactions. Resolving such complexity requires new spatially-defined approaches.

Thromboembolism and Adjuvant Endocrine Therapy (AET) in Hormone Receptor-Positive Early Breast Cancer (EBC): Did Treatment Evolution Change Incidence of the Adverse Event? A Meta-Analysis.

The adjuvant endocrine therapy (AET) of HR+ EBC has been changing in recent years. Aromatase inhibitors (AIs) as an upfront strategy (or as part of a switch strategy) have been added to the choice of Tamoxifen (T) alone. Increased TE risk is well known in T-treated patients, while AIs have shown a reduced TE rate.

Management of PALB2-associated breast cancer: A literature review and case report.

Germline pathogenic variants (PV) of the tumor suppressor gene are associated with an increased risk of breast, pancreatic, and ovarian cancer. In previous research, -associated breast cancer showed aggressive clinicopathological phenotypes, particularly triple-negative subtype, and higher mortality regardless of tumor stage, type of chemotherapy nor hormone receptor status. The identification of this germline alteration may have an impact on clinical management of breast cancer (BC) from the surgical approach to the systemic treatment choice.

Adjuvant Endocrine Therapy in Premenopausal Women With Hormone Receptor-Positive Early-Stage Breast Cancer: Risk Stratification in a Real-World Setting.

Background: Ovarian function suppression (OFS) and hormone therapy (HT) represent an adjuvant option in premenopausal hormone receptor-positive early breast cancer (HR+EBC). The SOFT-TEXT trials showed improved outcomes upon receiving aromatase inhibitors (AIs)/OFS.

Methods: In order to estimate the magnitude of absolute improvements, we conducted a retrospective study applying composite risk (CR) to 237 premenopausal HR+EBC patients.

ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk.

Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT).

Platinum-based chemotherapy and PARP inhibitors for patients with a germline BRCA pathogenic variant and advanced breast cancer (LATER-BC): retrospective multicentric analysis of post-progression treatments.

Introduction: Patients with breast cancer (BC) harbouring a germinal BRCA pathogenic variant (gBRCA-PV) may have an enhanced sensitivity to platinum-based chemotherapy (PBC) and PARP inhibitors (PARPi). As reported in ovarian cancer, however, sensitivity and resistance to these treatments could partially overlap. In patients with a gBRCA-PV and advanced BC (aBC), it remains unclear whether prior exposure to PARPi/PBC affects tumour response to subsequent PBC/PARPi, respectively.

Male breast cancer risk associated with pathogenic variants in genes other than BRCA1/2: an Italian case-control study.

Background: Germline pathogenic variants (PVs) in BRCA1/2 genes are associated with breast cancer (BC) risk in both women and men. Multigene panel testing is being increasingly used for BC risk assessment, allowing the identification of PVs in genes other than BRCA1/2. While data on actionable PVs in other cancer susceptibility genes are now available in female BC, reliable data are still lacking in male BC (MBC).

Personalized Systemic Therapies in Hereditary Cancer Syndromes.

Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population. The germline PVs promote cancer development, growth and survival, and may represent an ideal target for the personalized treatment of hereditary tumors. PARP inhibitors for the treatment of BRCA and PALB2-associated tumors, immune checkpoint inhibitors for tumors associated with the Lynch Syndrome, HIF-2α inhibitor in the VHL-related cancers and, finally, selective RET inhibitors for the treatment of MEN2-associated medullary thyroid cancer are the most successful examples of how a germline PVs can be exploited to develop effective personalized therapies and improve the outcome of these patients.