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GATA2 deficiency is a heterogeneous multi-system disorder characterized by a high risk of developing myelodysplastic syndrome (MDS) and myeloid leukemia. We analyzed the outcome of 65 patients reported to the registry of the European Working Group (EWOG) of MDS in childhood carrying a germline GATA2 mutation (GATA2mut) who had undergone hematopoietic stem cell transplantation (HSCT). At 5 years the probability of overall survival and disease-free survival (DFS) was 75% and 70%, respectively. Non-relapse mortality and relapse equally contributed to treatment failure. There was no evidence of increased incidence of graft-versus-host-disease or excessive rates of infections or organ toxicities. Advanced disease and monosomy 7 (−7) were associated with worse outcome. Patients with refractory cytopenia of childhood (RCC) and normal karyotype showed an excellent outcome (DFS 90%) compared to RCC and −7 (DFS 67%). Comparing outcome of GATA2mut with GATA2wt patients, there was no difference in DFS in patients with RCC and normal karyotype. The same was true for patients with −7 across morphological subtypes. We demonstrate that HSCT outcome is independent of GATA2 germline mutations in pediatric MDS suggesting the application of standard MDS algorithms and protocols. Our data support considering HSCT early in the course of GATA2 deficiency in young individuals.

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Germline SAMD9 and SAMD9L mutations (SAMD9/9Lmut) predispose to myelodysplastic syndromes (MDS) with propensity for somatic rescue. In this study, we investigated a clinically annotated pediatric MDS cohort (n = 669) to define the prevalence, genetic landscape, phenotype, therapy outcome and clonal architecture of SAMD9/9L syndromes. In consecutively diagnosed MDS, germline SAMD9/9Lmut accounted for 8% and were mutually exclusive with GATA2 mutations present in 7% of the cohort. Among SAMD9/9Lmut cases, refractory cytopenia was the most prevalent MDS subtype (90%); acquired monosomy 7 was present in 38%; constitutional abnormalities were noted in 57%; and immune dysfunction was present in 28%. The clinical outcome was independent of germline mutations. In total, 67 patients had 58 distinct germline SAMD9/9Lmut clustering to protein middle regions. Despite inconclusive in silico prediction, 94% of SAMD9/9Lmut suppressed HEK293 cell growth, and mutations expressed in CD34+ cells induced overt cell death. Furthermore, we found that 61% of SAMD9/9Lmut patients underwent somatic genetic rescue (SGR) resulting in clonal hematopoiesis, of which 95% was maladaptive (monosomy 7 ± cancer mutations), and 51% had adaptive nature (revertant UPD7q, somatic SAMD9/9Lmut). Finally, bone marrow single-cell DNA sequencing revealed multiple competing SGR events in individual patients. Our findings demonstrate that SGR is common in SAMD9/9Lmut MDS and exemplify the exceptional plasticity of hematopoiesis in children.

BACKGROUND: Treatment of de-novo metastatic breast cancer is usually centered around systemic therapy, with local therapy (surgery and radiation therapy) largely reserved for palliation in patients with significant symptoms from primary tumor. The efficacy of locoregional treatment like surgery and/or radiotherapy is still controversial and the debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. METHODS: All patients with de-novo MBC undergone surgical treatment between January 2015 and January 2020 at the Multidisciplinary Breast Center of the IRCCS A. Gemelli University Polyclinic Foundation in Rome were included in this study. The primary endpoint was overall survival (OS) after PT resection, the secondary endpoint was progression free survival (PFS). The survival analyses were done using Kaplan-Meier method. Patients and tumor characteristics were analyzed in an exploratory modality in order to identify prognostic factor. RESULTS: Forty-five patients received resection of the primary breast cancer (26 mastectomy and 19 breast conserving surgery). Median age of diagnosis was 53 years old (range 25-75 years old). Median follow-up was 25.67 months. The median OS was not reached with 75% of patients alive over 2 years from PT resection. The median PFS was not reached with 64% of patients alive over 2 years from PT resection. For both PFS and OS only the triple negative (TN) immunophenotype appears to be a prognostically unfavorable factor in multivariate analysis. CONCLUSIONS: In view of the low number of disease progression events and deaths, although our results are preliminary, surgical treatment of primary breast cancer in metastatic setting seems to be an option after systemic therapies in luminal and HER2 positive breast cancer. Randomized prospective trials for each immunophenotype are necessary in order to confirm this evidence.

No abstract available

The diagnosis of breast cancer (BC) during pregnancy is uncommon. It has varied among different studies from 1:10,000 to 1:3000 of all pregnancies, with a median age of 33 years. Pregnancy-associated BC represents a challenge in terms of clinical management to guarantee both maternal and fetal security in choosing the right treatment. This situation is complex and requires a multidisciplinary approach, including the surgeon, anesthesiologist, oncologist, radiotherapist, psychologist, and maternal–fetal medicine specialist. In the present review, we examined the management of pregnancy-associated BC, focusing on pathophysiologic background, risk factors, diagnosis, staging procedures, anesthesia, surgical management, and systemic treatment.

No abstract available

Sarcopenia is a geriatric syndrome characterized by losses of quantity and quality of skeletal muscle, which is associated with negative outcomes in older adults and in cancer patients. Different definitions of sarcopenia have been used, with quantitative data more frequently used in oncology, while functional measures have been advocated in the geriatric literature. Little is known about the correlation between frailty status as assessed by comprehensive geriatric assessment (CGA) and sarcopenia in cancer patients. We retrospectively analyzed data from 96 older women with early breast cancer who underwent CGAs and Dual X-ray Absorptiometry (DXA) scans for muscle mass assessment before cancer treatment at a single cancer center from 2016 to 2019 to explore the correlation between frailty status as assessed by CGA and sarcopenia using different definitions. Based on the results of the CGA, 35 patients (36.5%) were defined as frail. Using DXA Appendicular Skeletal Mass (ASM) or the Skeletal Muscle Index (SMI=ASM/heightˆ2), 41 patients were found to be sarcopenic (42.7%), with no significant difference in prevalence between frail and nonfrail subjects. Using the European Working Group on Sarcopenia in Older People (EWGSOP2) definition of sarcopenia (where both muscle function and mass are required), 58 patients were classified as “probably” sarcopenic; among these, 25 were sarcopenic and 17 “severely” sarcopenic. Only 13 patients satisfied both the requirements for being defined as sarcopenic and frail. Grade 3-4 treatment-related toxicities (according to Common Terminology Criteria for Adverse Events) were more common in sarcopenic and frail sarcopenic patients. Our data support the use of a definition of sarcopenia that includes both quantitative and functional data in order to identify frail patients who need tailored treatment.

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that allows to improve aesthetic results and patient quality of life. Traditionally, implant for reconstruction have been placed in a submuscolar (SM) plane, beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of prosthesis is increasingly used in order to avoid morbidities related to manipulation of PMM. The aim of the present study was to report our experience with 209 NSMs and IPBR using a prepectoral approach and polyurethane-coated implant without acellular dermal matrices (ADMs). METHODS: A retrospective review of breast cancer patients who underwent NSM followed by PP - IPBR from January 2018 to April 2021 was performed. Data were recorded in order to evaluate operative details, major complications and oncological outcomes. Aesthetic results and patient quality of life were measured by a specific “QOL assessment PRO” survey. RESULTS: Two hundred and nine patients (269 breasts) with PP - IPBR after NSM were included. Mean age was 47 (25-73) years and median follow-up was 14 (1-40) months. A simultaneous contralateral implant-based mammoplasty of symmetrization after unilateral NSM was carried out in six of 149 (4%) patients. Implant loss was observed in three of 209 patient (1.44%); two of 209 (0.96%) patients developed a full-thickness NAC necrosis that required excision. During follow-up one local relapse (0.48%) and two regional nodes recurrences (0,96%) was observed. Patient satisfaction, assessed using a personalized QOL Assessment PRO survey, in term of aesthetic results, chronic pain, shoulder dysfunction, sports activity, sexual and relationship life and skin sensibility, was excellent. CONCLUSIONS: Our experience shows that PP-IPBR using polyurethane-coated implant after NSM is a safe, reliable and effective alternative to traditional IPBR with excellent aesthetic outcomes and high patien

Neoadjuvant chemotherapy is increasingly being employed in the management of breast cancer patients. Efforts and resources have been devoted over the years to the search for an optimal strategy that can improve outcomes in the neoadjuvant setting. Today, a multidisciplinary approach with the application of evidence-based medicine is considered the gold standard for the improvement of oncological results and patient satisfaction. However, several clinical complications and psychological issues due to various factors can arise during neoadjuvant therapy and undermine outcomes. To ensure that health care needs are adequately addressed, clinicians must consider that women with breast cancer have a high risk of developing “unmet needs” during treatment, and often require a clinical intervention or additional care resources to limit possible complications and psychological issues that can occur during neoadjuvant treatment. This work describes a multidisciplinary model developed at “Fondazione Policlinico Universitario Agostino Gemelli” (FPG) in Rome in an effort to optimize treatment, ease the application of evidence-based medicine, and improve patient quality of life in the neoadjuvant setting. In developing our model, our main goal was to adequately meet patient needs while preventing high levels of distress.

Background: Worldwide, breast cancer (BC) is the most common malignancy in the female population. In recent years, its diagnosis in young women has increased, together with a growing desire to become pregnant later in life. Although there is evidence about the detrimental effect of chemotherapy (CT) on the menses cycle, a practical tool to measure ovarian reserve is still missing. Recently, anti-Mullerian hormone (AMH) has been considered a good surrogate for ovarian reserve. The main objective of this paper is to evaluate the effect of CT on AMH value. Methods: A systematic review and meta-analysis were conducted on the PubMed and Scopus electronic databases on articles retrieved from inception until February 2021. Trials evaluating ovarian reserves before and after CT in BC were included. We excluded case reports, case-series with fewer than ten patients, reviews (narrative or systematic), communications and perspectives. Studies in languages other than English or with polycystic ovarian syndrome (PCOS) patients were also excluded. AMH reduction was the main endpoint. Egger’s and Begg’s tests were used to assess the risk of publication bias. Results: Eighteen trials were included from the 833 examined. A statistically significant decline in serum AMH concentration was found after CT, persisting even after years, with an overall reduction of -1.97 (95% CI: -3.12, -0.82). No significant differences in ovarian reserve loss were found in the BRCA1/2 mutation carriers compared to wild-type patients. Conclusions: Although this study has some limitations, including publication bias, failure to stratify the results by some important factors and low to medium quality of the studies included, this metanalysis demonstrates that the level of AMH markedly falls after CT in BC patients, corresponding to a reduction in ovarian reserve. These findings should be routinely discussed during oncofertility counseling and used to guide fertility preservation choices in young women befo

No abstract available

Normal breast tissue undergoes great variations during a woman’s life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.

No abstract available

Clinical trials in cancer treatment are imperative in enhancing patients’ survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients’ accrual in clinical trials. We developed a specific platform, called “Digital Research Assistant” (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients’ records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients’ records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient’s data and clinical trial’s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.

Background: The aim of this study was to compare outcomes of immediate prosthetic breast reconstruction (IPBR) using traditional submuscular (SM) positioning of implants versus prepectoral (PP) positioning of micropolyurethane-foam-coated implants (microthane) without further coverage. Methods: We retrospectively reviewed the medical records of breast cancer patients treated by nipple-sparing mastectomy (NSM) and IPBR in our institution during the two-year period from January 2018 to December 2019. Patients were divided into two groups based on the plane of implant placement: SM versus PP. Results: 177 patients who received IPBR after NSM were included in the study; implants were positioned in a SM plane in 95 patients and in a PP plane in 82 patients. The two cohorts were similar for mean age (44 years and 47 years in the SM and PP groups, respectively) and follow-up (20 months and 16 months, respectively). The mean operative time was 70 min shorter in the PP group. No significant differences were observed in length of hospital stay or overall major complication rates. Statistically significant advantages were observed in the PP group in terms of aesthetic results, chronic pain, shoulder dysfunction, and skin sensibility (p < 0.05), as well as a trend of better outcomes for sports activity and sexual/relationship life. Cost analysis revealed that PP-IPBR was also economically advantageous over SM-IPBR. Conclusions: Our preliminary experience seems to confirm that PP positioning of a polyurethane-coated implant is a safe, reliable and effective method to perform IPBR after NSM.

OBJECTIVE: Triple-negative breast cancers (TNBC) include a heterogeneous group of diseases, characterized by the lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC that shows an overexpression of the androgen receptor (AR) defines the phenotype known as “luminal androgen receptor” (LAR), while the absence of the AR defines a “quadruple negative breast cancer” (QNBC). Several reports have associated AR positivity with a lower response to neoadjuvant chemotherapy (NAC), while divergent data have been reported about the impact of AR positivity on survival. The aim of this study was to retrospectively review our series of patients with TNBC tested for AR and submitted to NAC and compare pathologic complete response (pCR) rates in patients with a LAR phenotype or with QNBC. PATIENTS AND METHODS: The clinical records of all patients with TNBC tested for AR that underwent NAC at our Institution from January 1, 2015 to June 30, 2019 were reviewed. Histopathological features as well as ER, PgR, Ki67, HER2 values, clinical and pathological stage, and results of BRCA gene expression profiling were registered for all patients. RESULTS: Of the 145 TNBC patients treated by NAC, 20 (13.8%) had a LAR phenotype, while 125 (86.2%) had a QNBC. Overall, a pCR was achieved in 52 patients (35.8%). Patients with LAR phenotype had a lower rate of pCR as compared to patients with QNBC phenotype (25% vs. 37.6%). High Ki67 values (>50%) were observed less frequently in patients with a LAR phenotype (50% vs. 76.8% in QNBC). CONCLUSIONS: Our data seem to confirm that the LAR phenotype is associated to lower rates of pCR after neoadjuvant chemotherapy; routine assessment of AR expression in addition to classical biomarkers in patients with TNBC could help to better personalize treatment.

Sarcopenia is a geriatric syndrome characterized by losses of quantity and quality of skeletal muscle, which is associated with negative outcomes in older adults and in cancer patients. Different definitions of sarcopenia have been used, with quantitative data more frequently used in oncology, while functional measures have been advocated in the geriatric literature. Little is known about the correlation between frailty status as assessed by comprehensive geriatric assessment (CGA) and sarcopenia in cancer patients. We retrospectively analyzed data from 96 older women with early breast cancer who underwent CGAs and Dual X-ray Absorptiometry (DXA) scans for muscle mass assessment before cancer treatment at a single cancer center from 2016 to 2019 to explore the correlation between frailty status as assessed by CGA and sarcopenia using different definitions. Based on the results of the CGA, 35 patients (36.5%) were defined as frail. Using DXA Appendicular Skeletal Mass (ASM) or the Skeletal Muscle Index (SMI=ASM/heightˆ2), 41 patients were found to be sarcopenic (42.7%), with no significant difference in prevalence between frail and nonfrail subjects. Using the European Working Group on Sarcopenia in Older People (EWGSOP2) definition of sarcopenia (where both muscle function and mass are required), 58 patients were classified as “probably” sarcopenic; among these, 25 were sarcopenic and 17 “severely” sarcopenic. Only 13 patients satisfied both the requirements for being defined as sarcopenic and frail. Grade 3-4 treatment-related toxicities (according to Common Terminology Criteria for Adverse Events) were more common in sarcopenic and frail sarcopenic patients. Our data support the use of a definition of sarcopenia that includes both quantitative and functional data in order to identify frail patients who need tailored treatment.

Background: During the 2016 Assisi Think Tank Meeting (ATTM) on breast cancer, the panel of experts proposed developing a validated system, based on rapid learning health care (RLHC) principles, to standardize inter-center data collection and promote personalized treatments for breast cancer. Material and Methods: The seven-step Breast LArge DatabasE (BLADE) project included data collection, analysis, application, and evaluation on a data-sharing platform. The multidisciplinary team developed a consensus-based ontology of validated variables with over 80% agreement. This English-language ontology constituted a breast cancer library with seven knowledge domains: baseline, primary systemic therapy, surgery, adjuvant systemic therapies, radiation therapy, followup, and toxicity. The library was uploaded to the BLADE domain. The safety of data encryption and preservation was tested according to General Data Protection Regulation (GDPR) guidelines on data from 15 clinical charts. The system was validated on 64 patients who had undergone post-mastectomy radiation therapy. In October 2018, the BLADE system was approved by the Ethical Committee of Fondazione Policlinico Gemelli IRCCS, Rome, Italy (Protocol No. 0043996/18). Results: From June 2016 to July 2019, the multidisciplinary team completed the work plan. An ontology of 218 validated variables was uploaded to the BLADE domain. The GDPR safety test confirmed encryption and data preservation (on 5000 random cases). All validation benchmarks were met. Conclusion: BLADE is a support system for follow-up and assessment of breast cancer care. To successfully develop and validate it as the first standardized data collection system, multidisciplinary collaboration was crucial in selecting its ontology and knowledge domains. BLADE is suitable for multi-center uploading of retrospective and prospective clinical data, as it ensures anonymity and data privacy.

Background: Artificial Intelligence (AI) is increasingly used for process management in daily life. In the medical field AI is becoming part of computerized systems to manage information and encourage the generation of evidence. Here we present the development of the application of AI to IT systems present in the hospital, for the creation of a DataMart for the management of clinical and research processes in the field of breast cancer. Materials and methods: A multidisciplinary team of radiation oncologists, epidemiologists, medical oncologists, breast surgeons, data scientists, and data management experts worked together to identify relevant data and sources located inside the hospital system. Combinations of open-source data science packages and industry solutions were used to design the target framework. To validate the DataMart directly on real-life cases, the working team defined tumoral pathology and clinical purposes of proof of concepts (PoCs). Results: Data were classified into “Not organized, not ‘ontologized’ data”, “Organized, not ‘ontologized’ data”, and “Organized and ‘ontologized’ data”. Archives of real-world data (RWD) identified were platform based on ontology, hospital data warehouse, PDF documents, and electronic reports. Data extraction was performed by direct connection with structured data or text-mining technology. Two PoCs were performed, by which waiting time interval for radiotherapy and performance index of breast unit were tested and resulted available. Conclusions: GENERATOR Breast DataMart was created for supporting breast cancer pathways of care. An AI-based process automatically extracts data from different sources and uses them for generating trend studies and clinical evidence. Further studies and more proof of concepts are needed to exploit all the potentials of this system.

Breast conserving surgery has become the standard of care and is more commonly performed than mastectomy for early stage breast cancer, with recent studies showing equivalent survival and lower morbidity. Accurate preoperative lesion localization is mandatory to obtain adequate oncological and cosmetic results. Image guidance assures the precision requested for this purpose. This review provides a summary of all techniques currently available, ranging from the classic wire positioning to the newer magnetic seed localization. We describe the procedures and equipment necessary for each method, outlining the advantages and disadvantages, with a focus on the cost-effective preoperative skin tattoo technique performed at our centre. Breast surgeons and radiologists have to consider ongoing technological developments in order to assess the best localization method for each individual patient and clinical setting.

Acellular dermal matrices are biological materials of porcine, bovine, or human origin used as scaffold for reconstructive purpose in plastic surgery; these materials are well-tolerated and safely integrated in host tissues without causing resorption, contracture, and encapsulation thanks to their low antigenicity. Recently, human acellular dermal matrix has been used as a filler in breast-conserving surgery to improve aesthetic results. Adequate knowledge of biomaterials properties, appropriate skill, and careful compliance with some specific recommendations are mandatory in order to optimize outcomes and obtain a work of success.