B3 Breast Lesions: Positive Predictive Value and Follow-Up on a Large Single-Institution Series.

INTRODUCTION: Lesions of uncertain malignant potential (B3) represent 10% of core needle biopsies (CNBs) or vacuum-assisted breast biopsies (VABBs). Traditionally, B3 lesions are operated on. This study investigated the association between B3 subtypes and malignancy to determine the best management. METHODS: Pre- and postoperative histological reports from 226 patients, who had undergone excisional surgery for B3 lesions, following CNB or VABB, were retrospectively analyzed. The correlation between the CNB/VABB diagnosis and the final pathology was investigated, along with the correlation between malignancy upgrade and the type of mammographic lesion. The positive predictive value (PPV) of malignancy of B3 lesions was calculated by simple logistic regression. Patients without cancer diagnosis underwent a 7-y follow-up. RESULTS: Pathology showed 171 (75.6%) benign and 55 (24.3%) malignant lesions. The PPV was 24.3% (P = 0.043), including 31 (13.7%) ductal carcinomas in situ and 24 (10.6%) invasive carcinomas. The most frequently upgraded lesions were atypical ductal hyperplasia, 34.2% (P = 0.004), followed by lobular intraepithelial neoplasia, 27.5% (P = 0.025). The median diameter of mammographic lesions was 1.5 [0.9-2.5] cm, while for surgical specimens, it was 5 [4-7] cm (P < 0.0001). Mammographic findings and histology showed a significant correlation (P = 0.038). After a 7-y follow-up, 15 (8.9%) patients developed carcinoma, and 7 patients (4%) developed a new B3 lesion. CONCLUSIONS: We can conclude that atypical ductal hyperplasia and lobular intraepithelial neoplasia still require surgery for a significant PPV. Other types that lacked significance or confidence intervals were too wide to draw any conclusion.

Management of the axilla in breast cancer patients: critical review, regional modified Delphi consensus and implementation in the Tuscan breast network.

PURPOSE: Data from recently trials have provided practice-changing recommendations in management of the axilla in early breast cancer (eBC). However, further controversies have been raised, resulting in heterogeneous diffusion of these recommendations. Our purpose was to obtain a better homogeneity. MATERIAL AND METHODS: In 2021, the Tuscan Breast Network (TBN) established a consensus with the aim to update recommendations in this area. We performed a literature review on axillary management in eBC patients which led to an expert Delphi consensus aiming to explore the gray areas, build consensus and propose evidence-based suggestions for an appropriate management. Thereafter, we investigate their implementation in clinical practice. RESULTS: (1) DCIS patients should have SLN biopsy only in case of mastectomy or in conservative surgery if tumor is in a location that would preclude future nodal sampling or in case of a mass; (2) ALND may be omitted for 1-2 positive SLN patients undergoing BCS in T1-2 tumors with 1-2 SLN positive, eligible for whole-breast irradiation and adjuvant systemic therapies; (3) consider the option of RNI in patients with 1-3 positive lymph nodes and one or more high-risk characteristics; (4) the population identified in 2) should NOT undergo lymph node irradiation as an alternative to axillary surgery and (5) patients with clinically (pre-operatively) positive axilla, or undergoing primary systemic therapy, or outside the criteria reported in 2) must receive additional ALND and/or RT as per local policy. CONCLUSION: This consensus provided a practical tool to stimulate local and national breast surgical and radiotherapy protocols.

Anatomical assessment of local recurrence site in breast cancer patients after breast reconstruction and post-mastectomy radiotherapy: implications for radiation volumes and techniques.

INTRODUCTION: Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT. METHODS: Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored. RESULTS: Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases. CONCLUSIONS: The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed.

Percutaneous vacuum-assisted excision (VAE) of breast lesions of uncertain malignant potential (B3 lesions): a preliminary single-centre Italian experience.

PURPOSE: In recent years vacuum-assisted excision (VAE) has been described as an alternative treatment for some B3 lesions. This study aims to assess the effectiveness of using VAE to manage selected B3 lesions by quantifying the number of B3 lesions undergoing VAE, the malignant upgrade rate, and the complications encountered. MATERIALS AND METHODS: Our department evaluated all B3 lesions diagnosed between January 2019 and October 2021 and treated them with VAE. The data were collected during the initial biopsy and final histology based on VAE image guidance, also considering initial lesions and complications. The exclusion criteria were: B3 lesion of size > 20 mm, presence of a concomitant malignant lesion, lesion < 5.0 mm distant from the skin, nipple or pectoral muscle, phyllodes tumours or indeterminate B3 lesions. Lesions that upgraded to malignancy underwent surgical excision, while benign lesions performed radiological follow-ups. RESULTS: From 416 B3 lesions diagnosed, 67 (16.1%) underwent VAE. VAE was performed under X-ray (50/67) or ultrasound guidance (17/67). Five cases (7.5%) upgraded to a malignant lesion, 2 ADH, 2 LIN and one papillary lesion that underwent surgery. No malignancy or new lesions has occurred at the site of the VAE, with an average radiological follow-up of 14.9 months. CONCLUSIONS: VAE could be a safe and effective pathway for managing selected B3 lesions. Lesions initially subjected to CNB with ADH and LN outcome, before undergoing VAE, should perform a VAB for better tissue characterization and management.

Tumors carrying BRAF-mutations over-express NAMPT that is genetically amplified and possesses oncogenic properties.

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis, is up-regulated in several cancers, including metastatic melanoma (MM). The BRAF oncogene is mutated in different cancer types, among which MM and thyroid carcinoma (THCA) are prominent. Drugs targeting mutant BRAF are effective, especially in MM patients, even though resistance rapidly develops. Previous data have linked NAMPT over-expression to the acquisition of BRAF resistance, paving the way for therapeutic strategies targeting the two pathways. METHODS: Exploiting the TCGA database and a collection of MM and THCA tissue microarrays we studied the association between BRAF mutations and NAMPT expression. BRAF wild-type (wt) cell lines were genetically engineered to over-express the BRAF V600E construct to demonstrate a direct relationship between over-activation of the BRAF pathway and NAMPT expression. Responses of different cell line models to NAMPT (i)nhibitors were studied using dose-response proliferation assays. Analysis of NAMPT copy number variation was performed in the TCGA dataset. Lastly, growth and colony forming assays were used to study the tumorigenic functions of NAMPT itself. RESULTS: The first finding of this work is that tumor samples carrying BRAF-mutations over-express NAMPT, as demonstrated by analyzing the TCGA dataset, and MM and THC tissue microarrays. Importantly, BRAF wt MM and THCA cell lines modified to over-express the BRAF V600E construct up-regulated NAMPT, confirming a transcriptional regulation of NAMPT following BRAF oncogenic signaling activation. Treatment of BRAF-mutated cell lines with two different NAMPTi was followed by significant reduction of tumor growth, indicating NAMPT addiction in these cells. Lastly, we found that several tumors over-expressing the enzyme, display NAMPT gene amplification. Over-expression of NAMPT in BRAF wt MM cell line and in fibroblasts resulted in increased growth capacity, arguing in favor of oncogenic properties of NAMPT. CONCLUSIONS: Overall, the association between BRAF mutations and NAMPT expression identifies a subset of tumors more sensitive to NAMPT inhibition opening the way for novel combination therapies including NAMPTi with BRAFi/MEKi, to postpone and/or overcome drug resistance. Lastly, the over-expression of NAMPT in several tumors could be a key and broad event in tumorigenesis, substantiated by the finding of NAMPT gene amplification.

A new technique for the histological diagnosis of Paget's disease of the breast using a semiautomated core needle biopsy with a 14-gauge needle.

PURPOSE: The aim of our work is to illustrate a new technique for the histological diagnosis of Paget's disease (PD) using a core needle biopsy with a semiautomated 14-gauge needle called nipple-core needle biopsy (N-CNB). We report 3 years' experience in our senology unit. MATERIALS AND METHODS: Twenty-six women with 26 clinical of nipple-areola complex (NAC) changes with suspected PD and subjected to core needle biopsy using our new 14G semiautomated needle technique were included in our study group. Institutional review board approval was obtained for this retrospective analysis. A semiautomated biopsy gun with a 14-gauge, 15-cm-long needle was used for this new procedure. After a subcutaneous injection of anesthetic and spray-ice application to the NAC, the 14G needle was opened with the cradle exposed and positioned on the NAC with considerable pressure exerted on the same. The cradle was then closed by triggering the needle spring, and 2-4 core samples were withdrawn by moving the needle position each time. Clinical, instrumental and histological differences between the lesions that gave benign results after N-CNB and those that resulted PD were analyzed by applying the Fisher's exact test. RESULTS: After N-CNB, 13/26 lesions were found to be PD (50%) while 13/26 alterations were benign (50%). No malignant lesions were detected during the follow-up in patients with benign N-CNB results. The diagnosis of PD obtained with N-CNB was confirmed in all 13 cases by means of a histological analysis of the surgical specimens. No significant post-biopsy complications were recorded. Patients with PD more frequently presented nipple retraction (ρ = 0.0407) and associated suspicious (i.e., BI-RADS 4 and 5) mammographic (ρ = 0.0006) findings compared to patients whose N-CNB had given benign results and the difference was statistically significant. CONCLUSIONS: In conclusion, with this novel technique, we were able to obtain an easy, painless, major complication-free and accurate diagnosis of PD of the NAC using a semiautomated core needle biopsy with a 14-gauge needle.

Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study.

PURPOSE: For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk. METHODS: Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff's alpha (KA) and Gwet's AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression. RESULTS: Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05-6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35-5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34-10.23) were independently associated with a higher iIBC risk. CONCLUSIONS: Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.

Evaluation of contrast-enhanced digital mammography (CEDM) in the preoperative staging of breast cancer: Large-scale single-center experience.

One of the most important indications for contrast-enhanced breast imaging is the presurgical breast cancer (BC) staging. This is a large-scale single-center experience which evaluates the role of CEDM in presurgical staging and its impact on surgical planning. The aims of this retrospective study were to define the diagnostic performance of CEDM in the presurgical setting and to identify which types of patients could benefit from having CEDM. We selected 326 patients with BC who underwent CEDM as preoperative staging and had breast cancer-related surgery at our institution. We analyzed those cases in which CEDM led to additional imaging or biopsy and those in which it changed the type of surgery that was planned according to conventional breast imaging (CI) techniques (digital mammography, tomosynthesis and bilateral handheld ultrasound). CEDM sensitivity in identifying the index lesion and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy in the correct preoperative staging of BC of the whole population and in various subgroups were calculated. CEDM sensitivity for the index lesion was 98.8% (322/326), which led to additional breast imaging in 23.6% (77/326) of patients and additional biopsies in 17.5% (57/326). CEDM changed the type of surgery in 18.4% (60/326). In the preoperative breast cancer staging, CEDM sensitivity, specificity, PPV, NPV, and accuracy produced results of 93%, 98%, 90%, 98%, and 97%, respectively. CEDM performance was better in patients with palpable lesions. CEDM has an excellent diagnostic performance in the presurgical staging of BC. Symptomatic patients with palpable lesions benefitted most from preoperative CEDM, with a statistically significant difference compared with nonpalpable.

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy.

Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well-characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non-BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer-associated genes. The main clinical-pathologic characteristics of MBC in pathogenic variant carriers and non-carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 non-BRCA1/2 MBC patients were examined in our study. Twenty-seven of the non-BRCA1/2 MBC patients were carriers of germline pathogenic variants in other genes, including two APC p.Ile1307Lys variant carriers and one MUTYH biallelic variant carrier. PALB2 was the most frequently altered gene (1.2%) and PALB2 pathogenic variants were significantly associated with high risk of MBC. Non-BRCA1/2 pathogenic variant carriers were more likely to have personal (p = 0.0005) and family (p = 0.007) history of cancer. Results of our study support a central role of PALB2 in MBC susceptibility and show a low impact of CHEK2 on MBC predisposition in the Italian population. Overall, our data indicate that a multigene testing approach may benefit from appropriately selected patients with implications for clinical management and counseling of MBC patients and their family members.

Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study.

BACKGROUND: Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined. METHODOLOGY: Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation. RESULTS: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value < 0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416-0.614, p-value < 0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412-0.610, p-value < 0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman ρ = 0.727); fair for sTILs ≥ 25% (κ = 0.53) and for LPBC (κ = 0.49), but poor for sTILs as 10% increments (κ = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis. CONCLUSION: Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.

hERG1 channel expression associates with molecular subtypes and prognosis in breast cancer.

BACKGROUND: Breast cancer (BC) is the most frequent malignancy among females worldwide. Despite several efforts and improvements in early diagnosis and treatment, there are still tumors characterized by an aggressive behavior due to unfavorable biology, thus quite difficult to treat. In this view, searching for novel potential biomarkers is mandatory. Among them, in the recent years data have been gathered addressing ion channel as important players in oncology. METHODS: A retrospective pilot study was performed on 40 BC samples by means of immunohistochemistry in order to evaluate hERG1 potassium channels expression in BC. RESULTS: We provide evidence that hERG1 is expressed in all the BC samples analyzed. hERG1 expression was significantly associated with molecular subtype with the highest expression in Luminal A and the lowest in basal-like tumors (p = 0.001), tumor grading (the highest hERG1 expression in well-moderate differentiated tumors, p = 0.020), estrogen receptors (high hERG1 expression in ER-positive samples, p = 0.008) and Ki67 proliferative index (high hERG1 scoring in samples with low proliferative index, p = 0.038). Also, a p value close to significance was noticed for the association between hERG1 and HER2 expression (p = 0.079). At the survival analysis, patients with high hERG1 expression turned out to have a longer progression-free survival, although statistical significance was not reached (p = 0.195). The same trend was observed analyzing local relapse free-survival (LRFS) and metastases-free survival (MFS): patients with higher hERG1 scoring had longer LRFS and MFS (p = 0.124 and p = 0.071, respectively). CONCLUSIONS: The results of this pilot study provide the first evidence that the hERG1 protein is expressed in primary BC, and its expression associates with molecular subtype. hERG1 apparently behaves as a protective factor, since it contributes to identify a subset of patients with better outcome. Overall, these data suggest that hERG1 might be an additional tool for the management of BC, nevertheless further investigations are warranted to better clarify hERG1 role and clinical usefulness in BC.

Role of core needle biopsy in primary breast lymphoma.

Primary breast lymphoma (PBL) may mimic carcinoma clinically and also mammographic and ecographic distinction is subtle. Despite its rarity, incidence of PBLs has increased over the last four decades and continues to increase for younger women and for some subtypes, and for this reason it is increasingly important to achieve a preoperative pathological diagnosis using core needle biopsy (CNB) or fine-needle aspiration cytology (FNA). The aim of this retrospective study was to report our single-center experience in CNBs performed for histological diagnosis of PBL compared to FNA. From a total of 10,500 CNBs we found seven patients affected by PBL diagnosed at Careggi Florence University Hospital, between January 2000 and December 2016. Diffuse large B cell lymphoma (DLBCL) was the most frequent PBLs and on CNBs specimens was possible do the fluorescent in situ hybridization analysis to evaluate the presence of chromosomal translocation. CNB is an effective method for the assessment of PBLs, especially for DLBCL, in which a correct and fast classification could change the therapeutic approach and the prognosis.

EMSY copy number variation in male breast cancers characterized for BRCA1 and BRCA2 mutations.

PURPOSE: Male breast cancer (MBC) is a rare disease that shares some similarities with female breast cancer (FBC). Like FBC, genetic susceptibility to MBC can be referred to mutations in BRCA1 and, particularly, BRCA2 genes. However, only about 10 % of MBCs are caused by BRCA1/2 germ-line mutations, while the largest part are sporadic cancers and may derive from somatic alterations. EMSY, a BRCA2 inactivating gene, emerged as a candidate gene involved in the pathogenesis of sporadic FBC, and its amplification was suggested to be the somatic counterpart of BRCA2 mutations. Considering the relevant role of BRCA2 in MBC, we aimed at investigating the role of EMSY gene copy number variations in male breast tumors. METHODS: EMSY copy number variations were analyzed by quantitative real-time PCR with TaqMan probes in a selected series of 75 MBCs, characterized for BRCA1/2 mutations. RESULTS: We reported EMSY amplification in 34.7 % of MBCs. A significant association emerged between EMSY amplification and BRCA1/2 mutations (p = 0.03). We identified two amplification subgroups characterized by low and high amplification levels, with BRCA2-related tumors mostly showing low EMSY amplification. CONCLUSIONS: Our results show a high frequency of EMSY amplification in MBC, thus pointing to a role of EMSY in the pathogenesis of this disease. EMSY amplification may be a new feature that might uncover underlying molecular pathways of MBCs and may allow for the identification of MBC subgroups with potential clinical implication for targeted therapeutic approaches.

Impact of age on cytotoxic-induced ovarian failure in breast cancer treated with adjuvant chemotherapy and triptorelin.

AIM: This study analyzes our single-center, retrospective experience on 63 premenopausal breast cancer patients treated with monthly triptorelin and concomitant chemotherapy. PATIENTS & METHODS: Concomitant chemotherapy and triptorelin were adopted as part of premature ovarian failure prevention strategy. RESULTS: Age at diagnosis was the main factor influencing fertility preservation (p = 0.002). Compared with patients aged 41-45 years, the probability of menses resumption was almost threefold than for women aged 35-40 years, and significantly higher for women aged <35 years (hazard ratio: 9.0; p = 0.0001). The cumulative proportion among patients who resumed menses was 33.3% at 6 months, 75% at 12 months and 87.5% at 24 months. Seven patients attempted pregnancy, and five (71%) obtained healthy deliveries. CONCLUSION: We observed an acceptable rate of fertility preservation. Age at diagnosis influences fertility preservation.

Safety of eribulin mesylate and concomitant radiotherapy for metastatic breast cancer: a single-center experience.

AIM: This study evaluates, for the first time, the safety of eribulin in metastatic breast cancer patients concomitantly treated with palliative radiotherapy (RT). Patients & materials: A total of 17 patients were pretreated for metastatic breast cancer. Patients received eribulin mesylate and bone RT. RESULTS: The most frequent grade 3 hematologic adverse events were neutropenia (56%) and anemia (20%). Mean pain score decreased from 2 (baseline) to 0.7 (end of observation). Analgesic score remained stable (1.8 vs 1.6). Bone pain scores dropped within a few weeks and remained below baseline values throughout the analysis. The overall response rate was 29%, and the clinical benefit rate was 59%. CONCLUSION: Eribulin is characterized by a manageable safety profile also when combined with palliative RT.

Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial.

The purpose of this study was to report the efficacy and the safety profile on the subset of selected early breast cancer (BC) patients aged 70 years or older from a single-center phase 3 trial comparing whole breast irradiation (WBI) to accelerated partial breast irradiation (APBI) using intensity-modulated radiation therapy technique. Between 2005 and 2013, 520 patients aged more than 40 years old were enrolled and randomly assigned to receive either WBI or APBI in a 1:1 ratio. Eligible patients were women with early BC (maximum diameter 2.5 cm) suitable for breast conserving surgery. This study is registered with ClinicalTrials.gov, NCT02104895. A total of 117 patients aged 70 years or more were analyzed (58 in the WBI arm, 59 in the APBI arm). At a median follow-up of 5-years (range 3.4-7.0), the ipsilateral breast tumor recurrence (IBTR) rate was 1.9 % in both groups. No significant difference between the two groups was identified (log-rank test p = 0.96). The 5-year disease-free survival (DFS) rates in the WBI group and APBI group were 6.1 and 1.9 %, respectively (p = 0.33). The APBI group presented significantly better results in terms of acute skin toxicity, considering both any grade (p = 0.0001) and grade 2 or higher (p = 0.0001). Our subgroup analyses showed a very low rate and no significant difference in terms of IBTR, using both WBI and APBI. A significant impact on patients compliance in terms of acute and early late toxicity was shown, which could translate in a consistent improvement of overall quality of life.

Role of preoperative breast MRI in ductal carcinoma in situ for prediction of the presence and assessment of the extent of occult invasive component.

Ductal carcinoma in situ (DCIS) is a common neoplasm that may be associated with focal invasive breast cancer lesions. The aim of our study was to evaluate the role of preoperative magnetic resonance imaging (MRI) in determining occult invasive presence and disease extent in patients with preoperative diagnosis of pure DCIS. We analyzed 125 patients with postoperative pure DCIS (n = 91) and DCIS plus invasive component (n = 34). Diagnostic mammography (MRX) showed a size underestimation rate of 30.4% while MRI showed an overestimation rate of 28.6%. Comparing the mean absolute error between preoperative MRI and MRX evaluations and final disease extent, MRI showed an improved accuracy of 51.2%. In our analysis preoperative breast MRI showed a better accuracy in predicting postoperative pathologic extent of disease, adding strength to the growing evidences that preoperative MRI can lead to a more appropriate management of DCIS patients.

Upgrade rate to malignancy of uncertain malignant potential breast lesions (B3 lesions) diagnosed on vacuum-assisted biopsy (VAB) in screen detected microcalcifications: Analysis of 366 cases from a single institution.

PURPOSE: We retrospectively investigated clinical, radiological, and pathological features of B3 lesions associated with the risk of subsequent upgrade to malignancy. METHODS: We included consecutive vacuum-assisted biopsies (VABs) performed during 2011-2020 on suspicious microcalcifications not associated with other radiological signs diagnosed as B3 lesions and followed by surgical excision (SE) with definitive histological examination. Multiple logistic regression models were fitted to identify independent predictors of malignancy. RESULTS: Out of the 366 B3 lesions included, 56 (15.3 %, 95 % CI 11.8-19.4 %) had upgraded to malignancy at SE: of these, 42/366 (11.5 %, 95 % CI 8.4-15.2 %) and 14/366 (3.8 %, 95 % CI 2.1-6.3 %) were in situ and invasive carcinoma, respectively. At univariate analysis, variables positively associated with upgrade to malignancy were age ≥ 60 years (p = 0.008), mixed morphology (p = 0.018), scattered distribution (p = 0,001), extension of microcalcifications > 10 mm (p = 0.001), and mixed B3 lesion (p = 0.017). Among B3 subtypes, the highest rates of upgrade were observed for AIDEP, LCIS/LIN2, FEA + AIDEP, FEA + LCIS/LIN2, and FEA + AIDEP + LCIS/LIN2 (24.6 %, 21.4 %, 25.3 %, 20.0 % and 40.0 % respectively), while FEA and ALH/LIN1 had a lower rates of upgrade (7.5 % and 3.7 %, respectively). Multiple logistic regression analysis confirmed as risk factors older age (p = 0.029), larger extension (p = 0.001) and mixed morphology (p = 0.007) of microcalcifications, AIDEP (p = 0.011) among pure B3 lesions, and FEA + AIDEP (p = 0.001) and FEA + AIDEP + LCIS/LIN2 (p = 0.037) among mixed B3 lesions. CONCLUSIONS: Based on our findings, vacuum-assisted excision is reasonable as definitive management for FEA and ALH/LIN1, while SE should remain the mainstay of treatment for AIDEP and LCIS/LIN2, whose upgrade rates are too high to safely recommend VAE.

Pre-pectoral breast reconstruction with tissue expander entirely covered by acellular dermal matrix: feasibility, safety and histological features resulting from the first 64 procedures.

Background: Reconstructive options that can be used following conservative mastectomy, skin-, nipple-sparing and skin-reducing mastectomies, allow a remarkable variety of safe methods to restore the natural shape and aesthetics of the breast mound. In case of two-stage breast reconstruction, tissue expanders (TEs) are usually placed in a subpectoral position. The purpose of this retrospective cohort study is to evaluate the feasibility and safety of two-step reconstruction with TE in pre-pectoral position covered by acellular dermal matrix (ADM). Methods: Between March 2021 and May 2023, at the Azienda Ospedaliero Universitaria Careggi, University of Florence, 55 patients with BRCA 1/2 mutations or early breast cancer underwent conservative mastectomy with immediate pre-pectoral reconstruction using TE covered with ADM, followed by a second surgery with replacement of the expander with definitive prosthesis. Demographic, oncological, and histological data along with surgical complications were recorded. Results: A total of 64 conservative mastectomies were performed. In 2 patients (3.1%) complications were found that required reintervention and, in both cases, the TE had to be removed. Two patients developed hematoma and one patient developed seroma. Two patients showed wound dehiscence, both healed after conservative treatment and without implant exposure. No case of necrosis of the skin or nipple-areola complex has been observed, neither of capsular contracture. Capsule formed around TE was populated with cells and blood vessels and showed a thin area of synovial metaplasia. Conclusions: In selected cases it may be more cautious to perform a two-stage breast reconstruction after radical breast surgery by means of TEs. The placement of TEs in pre-pectoral position combines the excellent aesthetic and functional results of the pre-pectoral philosophy with a quite safer and more prudent two-step approach. Our experience reports optimistic results: the ADM covering the TE is seen successfully integrating during tissue expansion and becoming a vascularised new self-tissue. Complications rates are low and such ADM-assisted two-stage pre-pectoral reconstructive technique is a safe, practical, and reproducible method.