Search

Approximately 30–50% of hereditary breast and ovarian cancer (HBOC) is due to the presence of germline pathogenic variants in the BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) onco-suppressor genes, which are involved in DNA damage response. Women who carry pathogenic BRCA1 variants are particularly likely to develop breast cancer (BC) and ovarian cancer (OC), with a 45–79 percent and 39–48 percent chance, respectively. The BRCA1 c.4096+1G>A variant has been frequently ascertained in Tuscany, Italy, and it has also been detected in other Italian regions and other countries. Its pathogenetic status has been repeatedly changed from a variant of uncertain significance, to pathogenic, to likely pathogenic. In our study, 48 subjects (38 of whom are carriers) from 27 families were genotyped with the Illumina OncoArray Infinium platform (533,531 SNPs); a 20 Mb region (24.6 cM) around BRCA1, including 4130 SNPs (21 inside BRCA1) was selected for haplotype analysis. We used a phylogenetic method to estimate the time to the most recent common ancestor (MRCA) of BRCA1 c.4096+1G>A founder pathogenic variant. This analysis suggests that the MRCA lived about 155 generations ago—around 3000 years ago. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51–0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44–0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)−/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12–0.83; p = 0.02) and ER−/HER2− (OR = 0.41; 95% CI, 0.17–0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present pilot study, we developed and validated a new accurate, quick-to-use screening tool for stratifying frailty and the risk of mortality in oncological geriatric patients. Frailty detection with comprehensive geriatric assessment (CGA) is of pivotal importance in older cancer patients to avoid over- or under-treatment with chemotherapy and to detect those at increased risk for poor outcomes. Several tools have been developed to capture the complexity of frailty, but only a few were explicitly conceived for older patients with cancer. In this study, we consecutively enrolled older patients with breast cancer during the preoperative evaluation as the development cohort. We evaluated seventy patients with different types of cancer admitted to our OncoGeriatric Clinic for the validation cohort. We then evaluated the relationship between MPI and CGA items, and we finally realized a screening tool based on the combination of the significant variables, now called the Multidimensional Oncological Frailty Scale (MOFS). Background: Frailty detection with comprehensive geriatric assessment (CGA) is of pivotal importance in older patients with cancer to avoid over- or under-treatment and to detect those at increased risk for poor outcomes. Several tools have been developed to capture the complexity of frailty, but only a few were explicitly conceived for older adults with cancer. The study aimed at developing and validating a multidimensional, easy-to-use diagnostic tool for early-risk stratification in patients with cancer, called the Multidimensional Oncological Frailty Scale (MOFS). Methods: In this single-center prospective study, we consecutively enrolled 163 older women (age ≥ 75 years) with breast cancer, screened with a G8 score ≤ 14 during the outpatient preoperative evaluation at our breast centre, as the development cohort. Seventy patients with different types of cancer admitted to our OncoGeriatric Clinic served as the validation cohort. Using stepwise linear regression analysis, we evaluated the relationship between Multidimensional Prognostic Index (MPI) and CGA items, and, finally, realized a screening tool based on the combination of the significant variables. Results: The mean age of the study population was 80.4 ± 5.8 years, while the mean age of the validation cohort was 78.6 ± 6.6 years [42 women (60%)]. A composite model of the Clinical Frailty Scale, G8, and hand grip strength test showed a strong correlation with MPI (R= −0.712, p < 0.001). The MOFS accuracy in the prediction of mortality was optimal in both the development and the validation cohorts (AUC 0.82 and 0.87; p < 0.001 and 0.003, respectively). Conclusion: MOFS represents a new, accurate, quick-to-use frailty screening tool for stratifying the risk of mortality in geriatric cancer patients. [ABSTRACT FROM AUTHOR]

Aim of the study: The study aims to evaluate the performance of selected, high-volume, highly specialized, Italian Breast Centers at the time of COVID-19 pandemic (year 2020), compared to pre-pandemic time (year 2019), highlighting differences in terms of clinical presentation of breast cancer (BC) and therapeutic strategies. Methods: Patients' data were provided by the Senonetwork data warehouse Senonet. In order to examine changes in the surgical and oncological management of BC patients during different phases of COVID-19 pandemic, we took advantage of a selection quality indicators (QIs). We performed the analyses in two time-frames, from July to September (Jul-Sep) (2019 versus 2020) and from October to December (Oct-Dec) (2019 versus 2020). Results: Our analysis did not show any statistically significant difference in terms of diagnosis, surgical, oncological and radiation therapy procedures between the two trimesters 2019 and 2020. Nevertheless, we observed statistically significant differences, favoring 2020, when analyzing time-to surgery and time-to radiotherapy. On the other hand, we observed a significant reduction of neoadjuvant chemotherapy and we did not recollect any data on a major use of neoadjuvant endocrine therapy. Conclusions: In Italian Breast Centers, partners of Senonetwork, we could not observe any treatment delay or change in standard clinical practice for BC care during the 2020 pandemic year, compared to 2019 pre-pandemic year. This finding is in contrast with the globally reported decrease in the performance of the Italian Breast Centers due to the COVID-19 pandemic, and has to be linked to the sharp selection of Senonetwork Breast Centers. [ABSTRACT FROM AUTHOR]

• Despite the significance of oncoplastic procedure, an italian database is lacking. • Senonetwork established a multidisciplinary survey to assess their safety and efficacy. • Reconstructive outcomes were positive across low and high-volume centers. • After mastectomy, implant-based techniques are common. DTI reconstruction is advantageuos. • This contributes to the global understanding of effective strategies against breast cancer. [ABSTRACT FROM AUTHOR]

De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials. [ABSTRACT FROM AUTHOR]

Abstract Background and objectives We studied a large series of ductal carcinoma in situ with microinvasion (MIDC) an infrequent disease whose diagnosis and management are not well defined. Methods 17,431 cases of breast carcinoma were treated between 2011 and 2016 by ten Italian Breast Units. Our analysis included diagnostic and clinic-pathological characteristics, surgical management, and the use of adjuvant therapies. Results 15,091 cases (86.6%) were infiltrating carcinomas (IC), 2107 (12.1%) ductal carcinoma in situ (DCIS), and 233 (1.3%) MIDC. Age at diagnosis did not differ between DCIS and MIDC. MIDC were usually larger and expressed more frequently biologically aggressive features (higher Ki67 values, hormone receptor negativity and HER2/neu over-expression) (p < 0.01). Axillary lymph nodes were involved in 25 MIDC cases (12%), but >3 lymph nodes were involved in two cases only (1%). At multivariable analysis, only lymphovascular invasion (LVI) was associated with lymph node status (p < 0.01). Hormone therapy was prescribed in 388/1462 DCIS cases (26.5%), in 84/200 MIDC cases (42%), and in 11,086/14,188 IC cases (84.7%) (p < 0.01). Chemotherapy was administered in 28/190 MIDC cases (14.7%), and in 4080/11,548 IC cases (35.3%) (p < 0.001). Conclusions This is one of the largest studies of MIDC reported in the literature. Approximately 10% of DCIS harbor one or more foci of MIDC, and the latter often expresses aggressive biological features. LVI is a predictor of axillary node involvement, but this is infrequent and usually limited. Conservative surgery is performed less often than in DCIS, and adjuvant chemotherapy is less frequently utilized compared to IC. [ABSTRACT FROM AUTHOR]

Background and objectives: Cancer stem cells (CSCs) have been implicated in tumor initiation, recurrence, metastatic spread and poor survival in multiple tumor types, breast cancers included. CSCs selectively overexpress key mitochondrial-related proteins and inhibition of mitochondrial function may represent a new potential approach for the eradication of CSCs. Because mitochondria evolved from bacteria, many classes of FDA-approved antibiotics, including doxycycline, actually target mitochondria. Our clinical pilot study aimed to determine whether short-term pre-operative treatment with oral doxycycline results in reduction of CSCs in early breast cancer patients. Methods: Doxycycline was administered orally for 14 days before surgery for a daily dose of 200 mg. Immuno-histochemical analysis of formalin-fixed paraffin-embedded (FFPE) samples from 15 patients, of which 9 were treated with doxycycline and 6 were controls (no treatment), was performed with known biomarkers of "stemness" (CD44, ALDH1), mitochondria (TOMM20), cell proliferation (Ki67, p27), apoptosis (cleaved caspase-3), and neo-angiogenesis (CD31). For each patient, the analysis was performed both on pre-operative specimens (core-biopsies) and surgical specimens. Changes from baseline to post-treatment were assessed with MedCalc 12 (unpaired t- test) and ANOVA. Results: Post-doxycycline tumor samples demonstrated a statistically significant decrease in the stemness marker CD44 (p -value < 0.005), when compared to pre-doxycycline tumor samples. More specifically, CD44 levels were reduced between 17.65 and 66.67%, in 8 out of 9 patients treated with doxycycline. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate of nearly 90%. Similar results were also obtained with ALDH1, another marker of stemness. In contrast, markers of mitochondria, proliferation, apoptosis, and neo-angiogenesis, were all similar between the two groups. Conclusions: Quantitative decreases in CD44 and ALDH1 expression are consistent with pre-clinical experiments and suggest that doxycycline can selectively eradicate CSCs in breast cancer patients in vivo. Future studies (with larger numbers of patients) will be conducted to validate these promising pilot studies. [ABSTRACT FROM AUTHOR]

Background: The evolution in the surgical and diagnostic procedures, the attention to women's preferences, the case mix, and differences in professional practices may lead to a variability in the quality of breast cancer clinical pathway. To catch and manage this variability it is important to use valid measures. The aim of this paper is to examine the concurrent validity of the breast-conserving surgery (BCS) indicator and to provide evidence to guide the quality improvement process. Methods: The BCS indicator was calculated using hospital discharge records (HDRs) and was validated against surgical registry (SR) data in a random sample of 336 women undergoing breast cancer surgery in 2012 in two Tuscan teaching hospitals. The concurrent validity of BCS was examined by cross-tabulating patients using the ICD-9 CM codes for breast surgery obtained from the two data sources. Results: The analysis, carried out involving breast cancer professionals, highlighted that the large majority of interventions coded as "mastectomies" in HDRs are in fact reconstructing procedures, including nipple-sparing, skinsparing and skin-reducing mastectomies in SR. These results led us to refine the old algorithm, that calculates the proportion of breast-conserving surgery over the total number of breast interventions, and reclassify breast cancer surgical procedures into three categories: conservative, reconstructive and traditional mastectomy. Based on this new classification algorithm, the percentages of (I) reconstructive interventions were 16% at Florence TH and 38.3% at Pisa TH; (II) breast-conserving interventions were respectively 72.8 and 52.1%; and (III) mastectomies 11.2 and 9.6%. After adjusting for age in a logistic regression model, the percentages of reconstructive interventions at Florence and Pisa were respectively 22 and 34% and those of breast-conserving interventions 63 and 53%. Conclusions: Our results indicate that breast cancer care indicators should be refined by distinguishing reconstructive procedures (nipple/skin-sparing surgery with implant or breast tissue expander insertion) from traditional mastectomy. The involvement of breast care professionals in the choice of indicators proved to be crucial to capture the up-to-date breast cancer surgical practice and inform the quality improvement process. [ABSTRACT FROM AUTHOR]

Skin-reducing mastectomy is a single-stage technique that helps us to overcome the cosmetic inadequacy of a Type IV Wise pattern skin-sparing mastectomy (final T-inverted scar) in heavy and pendulous breasts by filling the lower-medial quadrant with adequate volume. It also conceals scars as an aesthetic operation and at the same time provides satisfactory and safe coverage of the implant. We report our experience with 22 skin-reducing mastectomies done for 18 women. We modified part of the original description of raising the dermal flap to refine the anatomical results. This flap was mobilised better by detachment of the lateral part of its insertion along the inframammary fold, and this allowed us to close the dermomuscular pouch inferiorly and laterally without raising the serratus anterior or limiting its rise. The total or partial preservation of the serratus muscle together with the creation of a force directed medially, as indicated by the dermal flap, reduced the risks of lateral dislocation of the implant and improved the lateral breast contour to give a more natural shape. Skin-reducing mastectomy is an oncologically safe skin-sparing mastectomy that solves all cosmetic problems and reduces complications of the original Type IV Wise pattern in medium to large breasts. Doing the mastectomy and reconstruction in a single stage aids the favourable psychological approach of the patient. We emphasise the use of our small modification to refine the contour of the breast and improve the aesthetic outcomes by giving a natural curvilinear profile. [ABSTRACT FROM AUTHOR]

Renal grafts from living donors represent an important source of organs, particularly for young patients with chronic renal failure. Laparoscopic donor nephrectomy is a relatively new technique, which has the potential to increase the pool of available kidney grafts by removing some disincentives to live donation. The technique used for left kidney donation at our center, the first to introduce laparoscopic live donor nephrectomy in Italy, is described in this report. To further reduce warm ischemia time, the kidney is preloaded inside the extraction bag and 2 staplers are used to transect the renal artery and vein. The spread of the new technique in our country and in the rest of Europe is likely to raise the issue of training in laparoscopic surgery for transplant surgeons. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival (OS). Taxane and anthracycline-containing chemotherapy (CT) is currently the main systemic treatment option for TNBC, while platinum-based chemotherapy showed promising results in the neoadjuvant and metastatic settings. An early arising of intrinsic or acquired CT resistance is common and represents the main hurdle for successful TNBC treatment. Numerous mechanisms were uncovered that can lead to the development of chemoresistance. These include cancer stem cells (CSCs) induction after neoadjuvant chemotherapy (NACT), ATP-binding cassette (ABC) transporters, hypoxia and avoidance of apoptosis, single factors such as tyrosine kinase receptors (EGFR, IGFR1), a disintegrin and metalloproteinase 10 (ADAM10), and a few pathological molecular pathways. Some biomarkers capable of predicting resistance to specific chemotherapeutic agents were identified and are expected to be validated in future studies for a more accurate selection of drugs to be employed and for a more tailored approach, both in neoadjuvant and advanced settings. Recently, based on specific biomarkers, some therapies were tailored to TNBC subsets and became available in clinical practice: olaparib and talazoparib for BRCA1/2 germline mutation carriers larotrectinib and entrectinib for neurotrophic tropomyosin receptor kinase (NTRK) gene fusion carriers, and anti-trophoblast cell surface antigen 2 (Trop2) antibody drug conjugate therapy for heavily pretreated metastatic TNBC (mTNBC). Further therapies targeting some pathologic molecular pathways, apoptosis, miRNAS, epidermal growth factor receptor (EGFR), insulin growth factor 1 receptor (IGF-1R), and androgen receptor (AR) are under investigation. Among them, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and EGFR inhibitors as well as antiandrogens showed promising results and are under evaluation in Phase II/III clinical trials. Emerging therapies allow to select specific antiblastics that alone or by integrating the conventional therapeutic approach may overcome/hinder chemoresistance. [ABSTRACT FROM AUTHOR]

The article reports a case study of a 35‐year‐old woman with necrotic phlegmon of the right breast, with a necrotic breast, fistulas and a smelly secretion. Topics include symptoms like a blunt trauma, unexplained multiple scars, a skin‐graft on her forearm, increased white‐blood‐cell‐count and wound swabs; mentions the vacuum assisted closure therapy with the use of gauze; and information on the multi‐step treatment‐strategy that required close cooperation between surgeons and dermatologists.