The past and future of angiogenesis as target for cancer therapy and prevention.

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. Since this concept was established in the Seventies, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy and prevention and on substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, ß-blockers, renin-angiotensin-aldosterone inhibitors, carnitines, and biguanides are reviewed.

Non-contrast MRI and post-mastectomy silicone breast implant rupture: preventing false positive diagnoses.

BACKGROUND: Breast implants are not lifelong, with implant rupture being the third leading cause of revisional surgery in augmented women. Noncontrast MRI is a reliable tool to assess implant integrity; however, false positive and false negative diagnoses have been reported due to an incorrect interpretation of MRI signs. This study aims to investigate the incidence of these misleading results, comparing MRI findings with intraoperative surgical observations and exploring signs of nonunivocal interpretation. MATERIALS AND METHODS: Between March 2019 and October 2022, our hospital, a referral center for breast cancer care, conducted 139 breast MRI examinations to evaluate implant integrity. Surgical intervention was deemed necessary for patients diagnosed with suspected or confirmed implant rupture at MRI. Those patients who did not undergo any surgical procedure (63 cases) or had surgery at different institutes (11 cases) were excluded. RESULTS: Among the 65 patients who underwent preoperative MRI and subsequent surgery at our institute, surgical findings confirmed the preoperative MRI diagnosis in 48 women. Notably, 17 women exhibited a discordance between MRI and surgical findings: three false negatives, 11 false positives and three possible ruptures not confirmed. Signs of nonunivocal or misleading interpretation were assessed on a patient-by-patient basis. The importance of obtaining detailed information about a patient's breast implant, including fill materials, number of lumens, manufacturer and shape, proved immensely beneficial for interpreting MRI signs accurately. CONCLUSION: Pre-MRI knowledge of implant details and a meticulous evaluation of non-univocal signs can aid radiologists in accurately assessing implant integrity, reducing the risk of unnecessary revisional surgeries, and potentially averting allegations of medical malpractice.

Tools to Guide Radiation Oncologists in the Management of DCIS.

Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.

CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype.

Importance: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation. Objectives: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival. Design, Setting, and Participants: This single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, with follow-up until January 31, 2023. Women with LBC seen at the European Institute of Oncology were included. Testing for germline CDH1, BRCA1, and BRCA2 genes was performed. Somatic profiling was assessed for germline CDH1 carriers. Main Outcomes and Measures: Accurate estimates of prevalence of germline CDH1 variants among patients with HLBC and the association of somatic sequence alteration with HLBC syndrome. The Kaplan-Meier method and a multivariable Cox proportional hazards regression model were applied for overall and disease-free survival analysis. Results: Of 5429 cases of primary LBC, familial LBC phenotype accounted for 1867 (34.4%). A total of 394 women with LBC were tested, among whom 15 germline CDH1 variants in 15 unrelated families were identified. Among these variants, 6 (40.0%) were P/LP, with an overall frequency of 1.5% (6 of 394). Of the 6 probands with P/LP CDH1 LBC, 5 (83.3%) had a positive family history of BC and only 1 (16.7%) had sporadic juvenile early-onset LBC. No germline BRCA1 and BRCA2 variants were identified in CDH1 carriers. An inactivating CDH1 mechanism (second hit) was identified in 4 of 6 explored matched tumor samples (66.7%) in P/LP germline carriers. The P/LP CDH1 LBC variant carriers had a significantly lower age at diagnosis compared with the group carrying CDH1 variants of unknown significance or likely benign (42.5 [IQR, 38.3-43.0] vs 51.0 [IQR, 45.0-53.0] years; P = .03). Conclusions and Relevance: In this cohort study, P/LP germline CDH1 variants were identified in individuals not fulfilling the classic clinical criteria for HDGC screening, suggesting that identification of these variants may provide a novel method to test women with LBC with early age at diagnosis and/or positive family history of BC.

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study.

Background: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. Methods: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. Findings: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and 65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Interpretation: Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Funding: Umberto Veronesi Foundation.

Points to consider regarding prophylactic total gastrectomy in germline CDH1 variant carriers.

Pathogenic germline CDH1 mutation confers high risk for developing diffuse gastric and lobular breast cancers in asymptomatic carriers. In these individuals, the estimated gastric cancer risk at 80 years of age is up to 70% for males and 56% for females. Due to this high-risk predisposition, prophylactic total gastrectomy is considered a unique life-saving approach in germline CDH1 carriers, as endoscopy often fails to detect early stage diffuse gastric carcinoma. However, surgical indication is controversial in some clinical contexts, with possible contraindications. This review discusses points against and in favor of a more aggressive surgical approach for consideration during the decision-making process.

The global gastric cancer consortium: an update from the Stomach cancer Pooling (StoP) project.

We updated to December 2023 the main findings of the stomach cancer pooling (StoP) project including about 13 000 cases and 31 000 controls from 29 case-control and 5 nested studies. The StoP project quantified more precisely than previously available the positive associations of tobacco smoking, high alcohol consumption, meat intake, selected occupations (e.g. agricultural and miners), gastric ulcer and family history with gastric cancer and the inverse associations with socioeconomic status and selected aspects of diet (fruits, including citrus fruits, vegetables, including allium and mushrooms, and polyphenols). No consistent associations were found with coffee, yoghurt and leisure-time physical activity, metformin or proton pump inhibitors use.

The multicenter experience in the multidisciplinary Italian breast units: a review and update.

A breast unit is a multidisciplinary center specialized in the management of women with breast diseases, including breast cancer (BC). It represents a care path, passing from screening activities to diagnostic investigations, from surgery to the definition of the therapeutic strategy, from psychophysical rehabilitation to long-term checks (follow-up), and up to genetic counseling. Since 2006, following a resolution issued by the European Parliament to urge member states to activate multidisciplinary breast centers by 2016, work has been underway throughout Italy to improve the management of women with BC. In Italy, the State-Regions agreement was signed on 18 December 2014, sanctioning the establishment of breast units. These centers must adhere to specific quality criteria and requirements. In 2020, the experts of the EUSOMA group (European Society of Breast Cancer Specialists), in their latest document published, expanded the requirements of the breast units. Furthermore, Senonetwork was founded in 2012 with the aim of allowing BC to be treated in breast units that comply with European requirements to ensure equal treatment opportunities for all Italian women. Indeed, the available data indicate that the BC patient has a greater chance of better treatment in the breast units with a multidisciplinary team, thus increasing the survival rate with a better quality of life, compared to those managed in nonspecialized structures. The present review is a perspective on the current Italian reality of breast units, updated with the available literature and the most recent epidemiological data from Senonetwork and AgeNaS.

Contrast-Enhanced Mammography (CEM) compared to Breast Magnetic Resonance (MRI) in the evaluation of breast lobular neoplasia.

PURPOSE: To compare the diagnostic performance (detection, assessment of correct disease extent and multifocality/centricity) of Contrast-Enhanced Mammography (CEM) Versus Breast Magnetic Resonance (MRI) in the study of lobular neoplasms. METHODS: We retrospectively selected all the patients who underwent surgery for a lobular breast neoplasm, either an in situ or an invasive tumor, and had undergone both breast CEM and MRI examinations during the pre-surgical planning. Wilcoxon Signed Rank test was performed to assess the differences between size measurements using the different methods and the post-surgical pathological measurements, considered the gold standard. The agreement in identifying multifocality/multicentricity among the different methods and the pathology was assessed using the Kappa statistics. RESULTS: We selected 19 patients, of which one presented a bilateral neoplasm. Then, the images of these 19 patients were analyzed, for a total of 52 malignant breast lesions. We found no significant differences between the post-surgical pathological size of the lesions and the calculated size with CEM and MRI (p-value of the difference respectively 0.71 and 0.47). In all 20 cases, neoplasm detection was possible both with CEM and MRI. CEM and MRI showed an excellent ability to identify multifocal and multicentric cases (K statistic equal to 0.93 for both the procedures), while K statistic was 0.11 and 0.59 for FFDM and US, respectively. CONCLUSION: The findings of this study suggest that CEM is a reliable imaging technique in the preoperative setting of patients with lobular neoplasm, with comparable results to breast MRI.

Clinical Implication of CDH1 Mutations in Genetic Testing for Diffuse Gastric Cancer Patients.

INTRODUCTION: The objective of this study was to reclassify published germline CDH1 variants identified in gastric cancer (GC) in accordance with the latest ClinVar definition and to correlate their pathogenicity with the established international clinical criteria for genetic testing. METHODS: The relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations in accord with PRISMA guidelines. The collected variants were classified according to the latest ClinVar definition into the following classes: benign (B), likely benign (LB), pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS). The McNemar test was used to compare the adequacy of current versus previous International GC Linkage Consortium (IGCLC) criteria. RESULTS: We reclassified a total of 247 CDH1 variants, and we identified that about 70% of B/LB variant carriers were not fulfilling the defined clinical criteria. Instead, all P/LP variants (100%) were associated with the hereditary diffuse gastric cancer (HDGC) phenotype fulfilling the 2020 ILGCC criteria, with a significant improvement (p = 0.025) compared to previous version. CONCLUSIONS: We conclude that germline CDH1 genetic testing is indicated only in families meeting the clinical criteria for the HDGC syndrome. This observation suggests that clinical phenotypes that do not clearly fulfill these criteria should not be considered for CDH1 genetic testing.

Advances in breast cancer risk modeling: integrating clinics, imaging, pathology and artificial intelligence for personalized risk assessment.

Breast cancer risk models represent the likelihood of developing breast cancer based on risk factors. They enable personalized interventions to improve screening programs. Radiologists identify mammographic density as a significant risk factor and test new imaging techniques. Pathologists provide data for risk assessment. Clinicians conduct individual risk assessments and adopt prevention strategies for high-risk subjects. Tumor genetic testing guides personalized screening and treatment decisions. Artificial intelligence in mammography integrates imaging, clinical, genetic and pathological data to develop risk models. Emerging imaging technologies, genetic testing and molecular profiling improve risk model accuracy. The complexity of the disease, limited data availability and model inputs are discussed. A multidisciplinary approach is essential for earlier detection and improved outcomes.

A Pictorial Exploration of Mammary Paget Disease: Insights and Perspectives.

Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple-areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed.

Future Directions in the Assessment of Axillary Lymph Nodes in Patients with Breast Cancer.

Background and Objectives: Breast cancer (BC) is a leading cause of morbidity and mortality worldwide, and accurate assessment of axillary lymph nodes (ALNs) is crucial for patient management and outcomes. We aim to summarize the current state of ALN assessment techniques in BC and provide insights into future directions. Materials and Methods: This review discusses various imaging techniques used for ALN evaluation, including ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography. It highlights advancements in these techniques and their potential to improve diagnostic accuracy. The review also examines landmark clinical trials that have influenced axillary management, such as the Z0011 trial and the IBCSG 23-01 trial. The role of artificial intelligence (AI), specifically deep learning algorithms, in improving ALN assessment is examined. Results: The review outlines the key findings of these trials, which demonstrated the feasibility of avoiding axillary lymph node dissection (ALND) in certain patient populations with low sentinel lymph node (SLN) burden. It also discusses ongoing trials, including the SOUND trial, which investigates the use of axillary ultrasound to identify patients who can safely avoid sentinel lymph node biopsy (SLNB). Furthermore, the potential of emerging techniques and the integration of AI in enhancing ALN assessment accuracy are presented. Conclusions: The review concludes that advancements in ALN assessment techniques have the potential to improve patient outcomes by reducing surgical complications while maintaining accurate disease staging. However, challenges such as standardization of imaging protocols and interpretation criteria need to be addressed. Future research should focus on large-scale clinical trials to validate emerging techniques and establish their efficacy and cost-effectiveness. Over-all, this review provides valuable insights into the current status and future directions of ALN assessment in BC, highlighting opportunities for improving patient care.

Germline CDH1 variants in hereditary diffuse gastric cancer syndrome with focus on younger women.

PURPOSE: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome. METHODS: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant. RESULTS: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021). CONCLUSIONS: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC.

Germline pathogenic variants in metaplastic breast cancer patients and the emerging role of the BRCA1 gene.

Metaplastic breast cancer (MpBC) is a rare, aggressive breast cancer (BC) histotype. Scarce information is available about MpBC genetic predisposition. Previous studies, mainly consisting of case reports, retrospective reviews and others on target therapies, pointed to a possible involvement of the BRCA1 gene in increasing MpBC risk, without ever confirming it. In this study, we retrospectively reviewed all BC patients counseled at our Institute for genetic testing of at least BRCA1 or BRCA2 (BRCA) genes and we found that 23 (23/5226 = 0.4%) were affected by MpBC. About 65% (15/23) of MpBC patients harbored a germline pathogenic variant (PV): 13 in BRCA1 (86.7%), including two patients who received genetic testing for known familial PV, one in TP53 (6.7%), and one in MLH1 (6.7%). We observed a statistically different frequency of MpBC in patients who carried a PV in the BRCA genes (13/1114 = 1.2%) vs. all other BC patients (10/4112 = 0.2%) (p = 0.0002). BRCA carriers proved to have an increased risk of developing MpBC compared to all other BC patients who were tested for BRCA genes (OR = 4.47; 95% CI: 1.95-10.23). Notably, MpBCs were diagnosed in 2.1% (13/610) of BRCA1 carriers. No MpBCs were observed in BRCA2 carriers (0/498 = 0%), revealing a statistically significant difference between the prevalence of MpBCs in BRCA1 and BRCA2 carriers (p = 0.0015). Our results confirmed that BRCA1 is involved in MpBC predisposition. Further studies on unselected patients are needed to elucidate the authentic role of BRCA1 and to explore the possible implication of other genes in MpBC predisposition.

Breast Digital Tomosynthesis versus Contrast-Enhanced Mammography: Comparison of Diagnostic Application and Radiation Dose in a Screening Setting.

This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients.

Ductal Carcinoma In Situ (DCIS) and Microinvasive DCIS: Role of Surgery in Early Diagnosis of Breast Cancer.

Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from "pure" DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.

FDG and Non-FDG Radiopharmaceuticals for PET Imaging in Invasive Lobular Breast Carcinoma.

Invasive lobular cancer (ILC) is the second most frequent histological type of breast cancer (BC) and includes a heterogeneous spectrum of diseases with unique characteristics, especially the infiltrative growth pattern and metastatic spread. [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is extensively used in oncology and BC patient evaluation. Its role in ILCs is considered suboptimal due to its low FDG avidity. Therefore, ILCs could benefit from molecular imaging with non-FDG tracers that target other specific pathways, contributing to precision medicine. This narrative review aims to summarize the current literature on the use of FDG-PET/CT in ILC and to discuss future opportunities given by the development of innovative non-FDG radiotracers.

Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience.

Gastric cancer (GC) has long been a 'Cinderella' among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7%). Seven out of fifty (14%) patients who underwent SGT for unknown mutations were carriers of a PV in CDH1 (n = 3), BRCA2 (n = 2), BRCA1 (n = 1), and MSH2 (n = 1), while one patient (2%) carried two variants of unknown significance (VUSs). CDH1 and MSH2 emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying five PVs (13.5%), including three (3/5:60%) in an HR gene (BRCA2, ATM, RAD51D) and at least one VUS in 13 patients (35.1%). Comparing PV carriers and non-carriers, we observed a statistically significant difference in PVs between patients with and without family history of GC (p-value: 0.045) or Lynch-related tumors (p-value: 0.036). Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspecific phenotypes, although it led to challenging results.

Metaplastic breast cancer: an all-round multidisciplinary consensus.

Metaplastic breast cancer (MpBC) is a rare and aggressive histologic subtype of breast cancer (BC) characterized by the presence of at least two cellular types, commonly epithelial and mesenchymal components. Despite growing evidence that MpBC is a unique entity, it has long been treated as a variant of nonspecial type (NST) BC. MpBC typically shows the phenotype of triple-negative breast cancer (TNBC), but compared to NST-TNBC, it is a relatively chemorefractory tumor associated with worse outcomes. Therefore, there is an urgent need to develop management guidelines specifically for MpBC to improve the prognosis of patients with early MpBC. This expert consensus aims to guide diagnosis and standardize clinical management of early MpBC among treating physicians. We provide guidance on the challenging radiological and pathological diagnosis of MpBC. Evidence on the involvement of genetic predisposition in the development of MpBC is also explored. We emphasize the importance of a multidisciplinary approach for the treatment of patients with early MpBC. The optimal surgery and radiotherapy approach is presented, as well as the opportunity offered by novel therapeutic approaches to increase treatment response in this chemoresistant subtype. Appropriate management of patients with MpBC is critical to reduce the high risk of local and distant recurrence that characterizes this disease.