A rare case of true carcinosarcoma of the breast

AbstractBackgroundTrue carcinosarcoma of the breast is an extremely rare condition, accounting for 0.08–0.2% of all breast malignancies.The correct definition of this tumor requires both a carcinomatous component and a malignant non-epithelial component of mesenchymal origin, without evidence of a transition zone between the two elements.Case presentationWe present a case of a 49-year-old woman presenting with a 4cm mass at the level of her left breast upper-outer quadrant with a histologic diagnosis of true carcinosarcoma of the breast.DiscussionThe most appropriate therapeutic regimens for breast carcinosarcoma are still unclear because of the rarity of this condition, but Breast Conserving Treatment (BCT) followed by adjuvant chemotherapy seems to provide a prognosis equalling that of usual Invasive Ductal Carcinoma of the breast

Breast conserving treatment for ductal carcinoma in situ in the elderly: Can radiation therapy be avoided? Our experience

AbstractIntroduction: Ductal Carcinoma In Situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 15–20% of all new breast cancers. If appropriately managed, DCIS has a small chance of impacting on patient life expectancy. Despite the possibility of a further recurrence or of a development in an invasive form, we are unable to select treatment of choice especially in the elderly. In particularly we risk an overtreatment of women at low risk of progression to invasive breast cancer. The aim of this study was to retrospectively evaluate the outcome of elderly patients affected by DCIS not undergoing Radiation Therapy (RT) after Breast Conserving Surgery (BCS). Material and methods: We reviewed our prospectively-maintained database from 1998 to 2013, selecting all women over 65 years old diagnosed with DCIS who did not receive RT for personal choice. We considered two groups, according to the risk of local recurrence (Low Risk (Group 1) vs. High Risk (Group 2)). Results: We identified 44 cases of DCIS treated with surgery alone or with surgery followed by adjuvant tamoxifen. 24 patients presented low risk of local recurrence (Group 1) and 20 had characteristics associated to high risk of local recurrence (Group 2). At a median follow-up of 66.3 months, no local recurrences have been described in group 1. No patients presented distant metastases, while 4 patients died for other causes. At a median follow-up of 72 months we observed 5 local recurrences in the second group (p < 0.05). Conclusion: Our results suggest that radiation therapy can be safely avoided in a selected group of elderly patients affected by DCIS

Contralateral risk reducing mastectomy in Non-BRCA-Mutated patients

The use of contralateral risk reducing mastectomy (CRRM) is indicated in women affected by breast cancer, who are at high risk of developing a contralateral breast cancer, particularly women with genetic mutation of BRCA1, BRCA2 and P53. However we should consider that the genes described above account for only 20-30% of the excess familiar risk. What is contralaterally indicated when genetic assessment results negative for mutation in a young patient with unilateral breast cancer? Is it ethically correct to remove a contralateral " healthy" breast? CRRM rates continue to rise all over the world although CRRM seems not to improve overall survival in women with unilateral sporadic breast cancer. The decision to pursue CRRM as part of treatment in women who have a low-to-moderate risk of developing a secondary cancer in the contralateral breast should consider both breast cancer individual-features and patients preferences, but should be not supported by the surgeon and avoided as first approach with the exception of women highly worried about cancer. Prospective studies are needed to identify cohorts of patients most likely to benefit from CRRM

Long Term Assessment of Anti-SARS-CoV-2 Immunogenicity after mRNA Vaccine in Persons Living with HIV

(1) Background: Waning of neutralizing and cell-mediated immune response after the primary vaccine cycle (PVC) and the first booster dose (BD) is of concern, especially for PLWH with a CD4 count ≤200 cells/mm3. (2) Methods: Neutralizing antibodies (nAbs) titers by microneutralization assay against WD614G/Omicron BA.1 and IFNγ production by ELISA assay were measured in samples of PLWH at four time points [2 and 4 months post-PVC (T1 and T2), 2 weeks and 5 months after the BD (T3 and T4)]. Participants were stratified by CD4 count after PVC (LCD4, ≤200/mm3; ICD4, 201–500/mm3, and HCD4, &gt;500/mm3). Mixed models were used to compare mean responses over T1–T4 across CD4 groups. (3) Results: 314 PLWH on ART (LCD4 = 56; ICD4 = 120; HCD4 = 138) were enrolled. At T2, levels of nAbs were significantly lower in LCD4 vs. ICD4/HCD4 (p = 0.04). The BD was crucial for increasing nAbs titers above 1:40 at T3 and up to T4 for WD614G. A positive T cell response after PVC was observed in all groups, regardless of CD4 (p = 0.31). (4) Conclusions: Waning of nAbs after PVC was more important in LCD4 group. The BD managed to re-establish higher levels of nAbs against WD614G, which were retained for 5 months, but for shorter time for Omicron BA.1. The T cellular response in the LCD4 group was lower than that seen in participants with higher CD4 count, but, importantly, it remained above detectable levels over the entire study period

Impact of contra-lateral breast reshaping on mammographic surveillance in women undergoing breast reconstruction following mastectomy for breast cancer

Background: The ultimate goal of breast reconstruction is to achieve symmetry with the contra-lateral breast. Contra-lateral procedures with wide parenchymal rearrangements are suspected to impair mammographic surveillance. This study aims to evaluate the impact on mammographic detection of mastopexies and breast reductions for contralateral adjustment in breast reconstruction. Patients and methods: We retrospectively evaluated 105 women affected by uni-lateral breast cancer who underwent mastectomy and immediate two-stage reconstruction between 2002 and 2007. We considered three groups according to the contra-lateral reshaping technique: mastopexy or breast reduction with inferior dermoglandular flap (group 1); mastopexy or breast reduction without inferior dermoglandular flap (group 2); no contra-lateral reshaping (group 3). We assessed qualitative mammographic variations and breast density in the three groups. Results: Statistically significant differences have been found when comparing reshaped groups with non reshaped groups regarding parenchymal distortions, skin thickening and stromal edema, but these differences did not affect cancer surveillance. The surveillance mammography diagnostic accuracy in contra-lateral cancer detection was not significantly different between the three groups (p ¼ 0.56), such as the need for MRI for equivocal findings at mammographic contra-lateral breast (p ¼ 0.77) and the need for core-biopsies to confirm mammographic suspect of contra-lateral breast cancer (p ¼ 0.90). Conclusions: This study confirms previous reports regarding the safety of mastopexies and breast reductions when performed in the setting of contra-lateral breast reshaping after breast reconstruction. Mammographic accuracy, sensitivity and specificity are not affected by the glandular re-arrangement. These results provide a further validation of the safety of current reconstructive paradigms

Humoral and cellular immune response elicited by mRNA vaccination against SARS-CoV-2 in people living with HIV (PLWH) receiving antiretroviral therapy (ART) according with current CD4 T-lymphocyte count

BACKGROUND: Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count. METHODS: PLWH on ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: 500/mm^{3}). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used. FINDINGS: Among 166 PLWH after 1 month from the second dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2% and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell 500 cell/mm^{3} and HIV-negative controls. A decreased RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm^{3}, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm^{}3 was comparable to HIV-negative population

Rapid interactome profiling by massive sequencing

We have developed a high-throughput protein expression and interaction analysis platform that combines cDNA phage display library selection and massive gene sequencing using the 454 platform. A phage display library of open reading frame (ORF) fragments was created from mRNA derived from different tissues. This was used to study the interaction network of the enzyme transglutaminase 2 (TG2), a multifunctional enzyme involved in the regulation of cell growth, differentiation and apoptosis, associated with many different pathologies. After two rounds of panning with TG2 we assayed the frequency of ORFs within the selected phage population using 454 sequencing. Ranking and analysis of more than 120 000 sequences allowed us to identify several potential interactors, which were subsequently confirmed in functional assays. Within the identified clones, three had been previously described as interacting proteins (fibronectin, SMOC1 and GSTO2), while all the others were new. When compared with standard systems, such as microtiter enzyme-linked immunosorbant assay, the method described here is dramatically faster and yields far more information about the interaction under study, allowing better characterization of complex systems. For example, in the case of fibronectin, it was possible to identify the specific domains involved in the interaction

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

Le funzioni di struttura per la caratterizzazione delle instabilita degli oscillatori

Lavoro eseguito nell'ambito della Convenzione in atto tra l'Amministrazione delle Poste e Telecomunicazioni e la Fondazione Ugo Bordoni. Relazione FUB: 3B06891SIGLEITItal