Impact of cavity shave margins in patients with ductal carcinoma in situ undergoing conserving breast surgery.

Aim: The main challenge during breast-conserving surgery (BCS) is to obtain clear margins, especially in patients with ductal carcinoma in situ (DCIS) due to the absence of well-defined nodules. Many surgical approaches have been used in an attempt to reduce the positive margin rate. The aim of this retrospective study is to compare the cavity shave margin technique with standard surgery and the intraoperative evaluation of surgical margins. Methods: This is a single-center retrospective study analyzing margin status, need for re-excision, and surgical time in a cohort of 227 patients who underwent surgery from September 2016 to September 2022. Results: In patients subjected to cavity shaving, we reported a significant reduction in positive margins of 17.1% versus 28.7% (p-value = 0.042). Also, a difference in terms of surgical re-excision was reported as p-value = 0.039 (12.4% versus 23.8%, respectively, for the cavity shave and control group). In the multivariate analysis, intraoperative evaluation of the margins was a risk factor for margins re-excision (Wald = 4.315, p = 0.038, OR: 2.331 [95% CI: 1.049-5.180]). Surgical time was lower in patients subjected to cavity shaves (p = 0.024), and the relative mean time was 68.4 min ± 37.1 min in the cavity shave group versus 93.9 min ± 40.6 min in the control group. Conclusion: The cavity shave margin technique in conserving breast surgery results in a reduction in positive margin rate, surgical re-excision, and operative time.

BIA-ALCL and BIA-SCC: Updates on Clinical Features and Genetic Mutations for Latest Recommendations.

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) and Breast Implant-Associated Squamous Cell Carcinoma (BIA-SCC) are emerging neoplastic complications related to breast implants. While BIA-ALCL is often linked to macrotextured implants, current evidence does not suggest an implant-type association for BIA-SCC. Chronic inflammation and genetics have been hypothesized as key pathogenetic players, although for both conditions, the exact mechanisms and specific risks related to breast implants are yet to be established. While the genetic alterations in BIA-SCC are still unknown, JAK-STAT pathway activation has been outlined as a dominant signature of BIA-ALCL. Recent genetic investigation has uncovered various molecular players, including MEK-ERK, PI3K/AKT, CDK4-6, and PDL1. The clinical presentation of BIA-ALCL and BIA-SCC overlaps, including most commonly late seroma and breast swelling, warranting ultrasound and cytological examinations, which are the first recommended steps as part of the diagnostic work-up. While the role of mammography is still limited, MRI and CT-PET are recommended according to the clinical presentation and for disease staging. To date, the mainstay of treatment for BIA-ALCL and BIA-SCC is implant removal with en-bloc capsulectomy. Chemotherapy and radiation therapy have also been used for advanced-stage BIA-ALCL and BIA-SCC. In-depth characterization of the tumor genetics is key for the development of novel therapeutic strategies, especially for advanced stage BIA-ALCL and BIA-SCC, which show a more aggressive course and poor prognosis.

Breast Cancer in Patients with Previous Endometriosis Showed Low Aggressive Subtype.

Background and Objectives: The association between endometriosis and breast cancer still remains controversial. The aim of this study was to investigate the different subtypes of breast cancer, immunohistochemical markers, hormone receptors, and ki67 proliferation indexes in patients with and without endometriosis and/or adenomyosis. Materials and Methods: All patients with endometriosis and breast cancer were enrolled. Women with endometriosis and breast cancer (Group BC+EN+) were compared to patients with breast cancer without endometriosis (group BC+EN-) and those with endometriosis without breast cancer (group BC-EN+). General population characteristics and histological and immunohistochemical subtypes of breast cancer were compared between groups. Results: Our study included 41 cases affected by both endometriosis and/or adenomyosis and breast cancer (Group BC+EN+) that were matched (1:2) with 82 patients affected only by breast cancer (group BC+EN-) and 82 patients affected only by endometriosis and/or adenomyosis (group BC-EN+). Group BC+EN+ presented a higher percentage of ER receptor expression (83% vs. 70%, p = 0.02), as well as lower values of Ki 67% (15% vs. 24%, p < 0.0001) and HER2+ (9.8% vs. 28%, p = 0.022). These findings were more evident when comparing patients with premenopausal status, while in postmenopausal patients, this difference was no longer significant. Regarding endometriosis, no statistical differences were observed in type or specific localization of the disease among the groups with and without breast cancer. Conclusions: Patients with endometriosis presented lower aggressive breast cancer rates with higher values of ER% and lower values of Ki 67 and HER2neu+. The type and severity of endometriotic diseases seemed not to influence breast cancer occurrence.

Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride in Non-invasive Axillary Staging in Breast Cancer: Are we Missing a Chance?

BACKGROUND/AIM: In the context of surgical de-escalation in early breast cancer (EBC), this study aimed to evaluate the contrast enhancement ultrasound (CEUS) sentinel lymph node (SLN) procedure as a non-invasive axillary staging procedure in EBC in comparison with standard SLN biopsy (SLNB). PATIENTS AND METHODS: A subanalysis of the AX-CES study, a prospective single-arm, monocentric phase 3 study was performed (EudraCT: 2020-000393-20). The study included patients with EBC undergoing upfront surgery and SLN resection, with no prior history of locoregional treatment, and weighing between 40-85 kg. All patients underwent the CEUS SLN procedure as a non-invasive axillary staging procedure, with CEUS SLN accumulation marked using blue dye. After the CEUS SLN procedure, all patients underwent the standard mapping procedure. Data on success rate, systemic reactions, mean procedure time, mean surgical procedure, mean procedure without axillary staging, CEUS SLN appearance (normal/pathological), SLN number, and concordance with standard mapping procedure were collected. RESULTS: After the CEUS SLN procedure, 29 LNs among 16 patients were identified and marked. In all cases, CEUS SLN revealed at least one LN enhancement. Six (37.50%) LNs were defined as pathological after the CEUS SLN procedure. Definitive staining of CEUS SLN pathology revealed metastatic involvement in four (66.67%) of the cases. Two SLNs were identified during the CEUS SLN procedure; however, owing to the low disease burden, no change in the surgical plan was reported. CONCLUSION: The CEUS SLN procedure shows promise as a technique for non-invasive assessment of the axilla, potentially enabling safe axillary de-escalation in EBC by estimating the axillary disease burden.

Surgical De-Escalation for Re-Excision in Patients with a Margin Less Than 2 mm and a Diagnosis of DCIS.

The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging.

Cavity Shave Margins in Breast Conservative Surgery a Strategy to Reduce Positive Margins and Surgical Time.

Background: Resection of additional tissue circumferentially around the cavity left by lumpectomy (cavity shave) was suggested to reduce rates of positive margins and re-excision. Methods: A single center retrospective study which analyzed margins status, re-excision, and surgical time in patients who underwent breast conserving surgery and cavity shave or intraoperative evaluation of resection margins. Results: Between 2021 and 2023, 594 patients were enrolled in the study. In patients subjected to cavity shave, a significant reduction in positive, focally positive, or closer margins was reported 8.9% vs. 18.5% (p = 0.003). No difference was reported in terms of surgical re-excision (p < 0.846) (5% vs. 5.5%). Surgical time was lower in patients subjected to cavity shave (<0.001). The multivariate analysis intraoperative evaluation of sentinel lymph node OR 1.816 and cavity shave OR 2.909 were predictive factors for a shorter surgical time. Excluding patients subjected to intraoperative evaluation of sentinel lymph node and patients with ductal carcinoma in situ, patients that underwent the cavity shave presented a reduced surgical time (67.9 + 3.8 min vs. 81.6 + 2.8 min) (p = 0.006). Conclusions: Cavity shaving after lumpectomy reduced the rate of positive margins and it was associated with a significant reduction in surgical time compared to intraoperative evaluation of resection margins.

A primary luminal/HER2 negative breast cancer patient with mismatch repair deficiency.

Here, we present the case of a 47-year-old woman diagnosed with luminal B breast cancer subtype and provide an in-depth analysis of her gene mutations, chromosomal alterations, mRNA and protein expression changes. We found a point mutation in the FGFR2 gene, which is potentially hyper-activating the receptor function, along with over-expression of its ligand FGF20 due to genomic amplification. The patient also harbors somatic and germline mutations in some mismatch repair (MMR) genes, with a strong MMR mutational signature. The patient displays high microsatellite instability (MSI) and tumor mutational burden (TMB) status and increased levels of CTLA-4 and PD-1 expression. Altogether, these data strongly implicate that aberrant FGFR signaling, and defective MMR system might be involved in the development of this breast tumor. In addition, high MSI and TMB in the context of CTLA-4 and PD-L1 positivity, suggest the potential benefit of immune checkpoint inhibitors. Accurate characterization of molecular subtypes, based on gene mutational and expression profiling analyses, will be certainly helpful for individualized treatment and targeted therapy of breast cancer patients, especially for those subtypes with adverse outcome.

Socioeconomic Impact of OncotypeDX on Breast Cancer Treatment: Preliminary Results.

BACKGROUND/AIM: Breast cancer (BC) is the most prevalent oncological diagnosis worldwide. Molecular subtyping has provided valuable insights for treatment decisions, but challenges remain in adjuvant treatment for hormone receptor (HR)-positive/HER2-negative luminal BC (LBC). Multigene markers like Oncotype DX have emerged to provide more precise prognostic information. This study aimed to evaluate the influence of gene expression panels on fear of cancer recurrence (FCR), quality of life (QoL), and healthcare-related greenhouse emissions. PATIENTS AND METHODS: A monocentric retrospective analysis was conducted using a prospective database of patients undergoing Oncotype DX. QoL assessments were performed using the Short Breast Health Perception Questionnaire (BHPQ) and Life Satisfaction Questionnaire (LSQ-32). Reductions in hospital visits and travel distance were analyzed. RESULTS: Twenty-eight patients underwent Oncotype DX testing. Of these, 17.85% received adjuvant chemotherapy based on the recurrence score (RS). The implementation of Oncotype DX resulted in a significant reduction in hospital visits, travel distance, and healthcare-related greenhouse gas emissions. QoL assessments using BHPQ and LSQ-32 showed lower levels of FCR and improved QoL in various domains for patients who received hormone therapy (HT) alone. CONCLUSION: The implementation of Oncotype DX in clinical practice has the potential to reduce overtreatment, decrease healthcare-related greenhouse gas emissions, and improve QoL. Lower levels of FCR and improved QoL were observed in patients who received HT-only based on the RS score.

A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy.

Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.

BACKGROUND: The identification in breast cancer (BC) of novel genetic biomarkers regulating natural killer (NK) cell function, including the HLA, KIR, and CD16A (FCGR3A), may be still a challenge. OBJECTIVE: We aimed to evaluate whether the combined effect of these polymorphisms has an impact on BC susceptibility and progression. METHODS: 47 BC Italian patients and healthy individuals (39 females and 66 males/females) were genotyped by Sanger sequencing (HLA-C exon 2-4 and FCGR3A-158V/F, 48L/R/H) and PCR-SSP typing (KIR genes). RESULTS: HLA-C gene allele analysis showed the group C1, with HLA-C*07:02:01 allele, to be significantly associated with tumor progression (16.7% vs. 4.0%, p=0.04, OR=4.867), and instead, group C2, with HLA-C*05:01:01, was protective against disease susceptibility (0.0% vs. 7.2%, p=0.019, OR=0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (pcorr.=0.022) and an increased combined presence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to earlier stages (66.7% vs. 19.2%, p=0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p=0.012, OR=5.020) or with lymph node involvement (p=0.008, OR=6.375). Lastly, we identified different combinations of the FCGR3A-48/158 variants and KIR genes in BC patients compared to controls. CONCLUSION: Our findings suggest that in the development of BC probably exists a disorder of the NK innate immunity influenced by KIR/HLA-C gene content and FCGR3A-158 polymorphisms and that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients in therapy.

Dynomics: A Novel and Promising Approach for Improved Breast Cancer Prognosis Prediction.

Traditional imaging techniques for breast cancer (BC) diagnosis and prediction, such as X-rays and magnetic resonance imaging (MRI), demonstrate varying sensitivity and specificity due to clinical and technological factors. Consequently, positron emission tomography (PET), capable of detecting abnormal metabolic activity, has emerged as a more effective tool, providing critical quantitative and qualitative tumor-related metabolic information. This study leverages a public clinical dataset of dynamic 18F-Fluorothymidine (FLT) PET scans from BC patients, extending conventional static radiomics methods to the time domain-termed as 'Dynomics'. Radiomic features were extracted from both static and dynamic PET images on lesion and reference tissue masks. The extracted features were used to train an XGBoost model for classifying tumor versus reference tissue and complete versus partial responders to neoadjuvant chemotherapy. The results underscored the superiority of dynamic and static radiomics over standard PET imaging, achieving accuracy of 94% in tumor tissue classification. Notably, in predicting BC prognosis, dynomics delivered the highest performance, achieving accuracy of 86%, thereby outperforming both static radiomics and standard PET data. This study illustrates the enhanced clinical utility of dynomics in yielding more precise and reliable information for BC diagnosis and prognosis, paving the way for improved treatment strategies.

Anxiety and Fear of Breast Cancer Patients During and After the COVID-19 Era.

BACKGROUND/AIM: Coronavirus-19 (COVID-19) pandemic had a huge impact on medical resource allocation. While it is clear that the surgery refusal rate of patients with breast cancer (BC) was higher during the pandemic, long-term effect of COVID-19 pandemic on hospital admission in the post-pandemic period has not been fully evaluated. This study aimed to estimate how patients' behavior changed following the pandemic and whether the cross-infection risk is still influencing patients' decision-making process. PATIENTS AND METHODS: Between the 16th of January and 18th of March 2020, between 19th of March 2020 and the 20th of March 2020, and between 19th of March 2023 and the 20th of March 2023, 266 patients were enrolled and divided into PRE-COVID-19, COVID-19, and POST-COVID-19 groups, respectively. A total of 137 patients with a suspected breast lesion (SBL) were divided into 3 groups: PRE-COVID-19-SBL, COVID-19-SBL, and POST-COVID-19-SBL groups. In addition, 129 BC patients were divided into PRE-COVID-19-BC, COVID-19-BC and POST-COVID-19-BC groups. Patient characteristics including age, marital status, SBL/BC diameter, personal and family history of BC, clinical stage and molecular subtype were recorded. Procedure refusal (PR) and Surgical refusal (SR) were also recorded with their reason. RESULTS: BC and SBL analysis showed no difference in pre-treatment characteristics (p>0.05). While higher rate of PR and SR rates were reported in COVID-19-SBL and COVID-19-BC groups when compared with PRE-COVID-19 (p=0.003, p=0.013, respectively) and POST-COVID-19 (p=0.005, p=0.004, respectively) groups, no statistical difference was found between PRE-COVID-19 and POST-COVID-19 subanalysis. CONCLUSION: Thanks to preventive measures, COVID-19 does not currently seem to affect the decision-making process of patients with BC.

Awake Breast Surgery: A Systematic Review.

BACKGROUND/AIM: Awake surgery has become a valid alternative to general anesthesia in many surgery fields. This technique played a very important role during the COVID-19 period. The growing use of this technique has many advantages. We performed a systematic review to study the potentialities of awake breast surgery. MATERIALS AND METHODS: We searched Pubmed, Embase, and Cochrane library database and retrieved a total of 109 records. Forty-nine of them were excluded as unsuitable. Finally, we selected a total of 12 records concerning different types of studies for topic appropriateness. Three reviewers reviewed independently each record. RESULTS: Five articles analyzing the sustainability of awake surgery during the COVID-19 period were selected. In addition, one article analyzing the impact on the immune system and six articles and eight case reports analyzing anesthetic techniques were also selected. The studies analyzing awake breast surgery during the COVID-19 period showed advantages in terms of sustainability and length of hospitalization. The study analyzing the immune response after awake breast surgery showed lesser lymphocyte response than the general anesthesia group. The studies analyzing anesthetic techniques in awake breast surgery showed that the nerve blocks allow good level of safety and postoperative pain control. CONCLUSION: The awake breast surgery and fast track implementation shortened hospital stays and reduced costs, without influencing the surgical results. Furthermore, awake breast surgery reduced surgical stress compared to general anesthesia. Among the various anesthetic techniques, nerve blocks are the most advantageous in terms of safety and efficacy compared to epidural anesthesia.

From Patient Reported Outcome Measure (PROM) to Environment Related Outcome Measure (EROM): Towards "Green Breast Surgery".

Climate change is a global issue that has had significant impacts on public health and healthcare policy worldwide. The direct impact of climate change on healthcare has been associated with extreme weather events, resulting in a higher demand for disaster management resources and reduced healthcare access. Moreover, the increase of zoonotic spillover effects has increased the risk of transmission of different diseases, including COVID-19. The healthcare industry alone is responsible for 4.4% of greenhouse gas global emissions. The surgical theatre is a resource-intense healthcare activity and a major carbon emitter, thus surgical processes require rethinking. This article proposes the introduction of environmental-related outcome measures in clinical trials, which will associate highest clinical standards to a reduced impact of care on climate change. Breast cancer care may represent a model disease for the implementation of evidence-based protocols, such as Green Breast Surgery, aiming to optimize the carbon footprint of care without affecting oncological and non-oncological outcomes. Physicians and healthcare workers worldwide should be aware of the importance of addressing environmental issues in healthcare policy, implementing programs to reduce their carbon footprint, and contributing to a more sustainable future.

Vacuum-assisted Evacuation (VAEv) of Symptomatic and/or Voluminous Breast Haematomas Following Surgeries and Percutaneous Procedures.

BACKGROUND/AIM: Among postoperative complications in breast surgery, postoperative hematoma is the most common occurrence. While mostly self-limited, in some cases surgical revision is mandatory. Among percutaneous procedures, preliminary studies demonstrated the efficacy of vacuum-assisted breast biopsy (VAB) in evacuating postprocedural breast hematomas. However, no data are available regarding VAB evacuating postoperative breast hematomas. Therefore, the present study aimed to investigate the efficacy of the VAB system in evacuating postoperative and postprocedural hematoma, symptom resolution, and avoidance of surgery. PATIENTS AND METHODS: From January 2016 to January 2020, patients with ≥25 mm symptomatic breast hematomas developed after breast-conserving surgery (BCS) and percutaneous procedures were retrospectively enrolled from a perspective-maintained database. Hematoma maximum diameter, estimated hematoma volume, total procedure time, and visual analog scale (VAS) score before ultrasound (US) vacuum-assisted evacuation (VAEv) were recorded. At one-week VAS score, residual hematoma volume, and complications were recorded. RESULTS: Among 932 BCSs and 618 VAB procedures, a total of 15 late postoperative hematomas were recorded (9 after BCS and 6 after VAB). Preoperative median diameter was 43.00 (35.50-52.50) mm and median volume 12.60 (7.35-18.30) mm3 Regarding VAEv, median time recorded was 25.92 (21.89-36.81) min. At one week, the median hematoma reduction was 83.00% (78.00%-87.5%) with a statistically significant VAS reduction (5.00 vs. 2.00; p>0.001). No surgical treatment was needed and only one case of seroma occurred. CONCLUSION: VAEv represents a promising safe, time and resource-sparing treatment modality for the evacuation of breast hematomas, potentially decreasing the rate of reoperation after surgery.

Surgical Treatments for Ductal Carcinoma In Situ (DCIS) in Elderly Patients.

BACKGROUND/AIM: Despite an aging population, there is no consensus regarding ductal carcinoma in situ (DCIS) treatment for elderly women. Breast surgery can be well tolerated even in elderly patients. The aim of this study is to evaluate the surgical management of DCIS in elderly patients. PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS from 2016 to 2022 at our Breast Unit and divided our population according to age. RESULTS: Out of 231 patients with DCIS, 45 (19.5%) were elderly. The Charlson comorbidity index and American Society of Anesthesiology (ASA) score was significantly higher in the elderly (p<0.001 for both). Among the elderly, 10 (22.2%) patients received upstaging diagnoses, versus 18 (9.7%) in the control (p=0.048). Twelve (26.7%) of the elderly patients underwent sentinel lymph node biopsy, versus 93 (50%) in the control group (p=0.005). No difference was reported between groups in terms of breast conserving surgeries performed. A higher incidence of surgeries performed using local anesthesia was reported in the elderly group (p=0.041). Thirty-day surgical complications, according to Clavien-Dindo, did not show significant differences. CONCLUSION: Despite higher comorbidity and ASA score, breast surgery is safe and feasible in elderly patients. Due to the higher risk of upstaging to invasive ductal carcinoma, surgery should be performed but sentinel lymph node biopsy should be omitted, owing to the low risk of lymph node metastasis and lower use of adjuvant treatments.

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies.

Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients.

Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride for Identification of Sentinel Lymph Nodes During Breast Cancer Surgery: A Clinical Trial.

BACKGROUND/AIM: Sentinel lymph node (SLN) procedures have gained popularity in early breast cancer thanks to the reduction of surgical side-effects. The standard SLN mapping procedure uses 99mTc-nanocolloid human serum albumin with/without blue dye; limitations include logistical challenges and adverse reactions. Recently, contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride has emerged as a promising technique for SLN mapping. Our study aimed to compare the CEUS technique with the standard isotope method. MATERIALS AND METHODS: AX-CES, a prospective, monocentric, single-arm phase-3 study was designed (EudraCT: 2020-000393-20). Inclusion criteria were histologically diagnosed early breast cancer eligible for upfront surgery and SLN resection, bodyweight 40-85 kg, and no prior history of ipsilateral surgery or radiotherapy. All patients underwent CEUS prior to surgery and blue dye injection was performed in areas with contrast accumulation. After the experimental procedure, all patients underwent the standard mapping procedure and SLN frozen section assessment was performed. Data on the success rate, systemic reactions, mean procedure time, CEUS appearance, SLN number, and concordance with standard mapping procedure were collected. RESULTS: Among 16 cases, a median of two SLNs were identified during CEUS. In all cases, at least one SLN was identified by CEUS (100%). In six cases, SLNs were classified during CEUS as abnormal, which was confirmed by definitive staining in four cases. After the standard mapping technique, in 15 out of the 16 cases (87.50%), at least one SLN from the standard mapping procedure was marked with blue dye in the CEUS procedure. In our series, sensitivity and specificity of SLN detection by CEUS were 75% and 100%, respectively. CONCLUSION: CEUS is a safe and manageable intraoperative procedure. When compared with standard techniques, US appearance during CEUS may provide additional information when associated with histological assessment.

Awake Breast Conservative Surgery: A Strategy to Shorten Surgical Waiting Lists During and Post COVID-19 Emergency.

BACKGROUND/AIM: SARS-CoV-2 with a dramatical worldwide spread, impacted greatly daily life and healthcare. In order to avoid delay in cancer treatment, many strategies and measures were implemented. The Awake breast surgery was a strategy implemented in our Unit during the pandemic, aimed to reduce operatory room occupancy and increase the number of procedures performed during the daily surgical session. The aim of the study was to evaluate how the use of this strategy has changed before and after the advent of the COVID-19 pandemic, and its relative benefits. PATIENTS AND METHODS: This was a retrospective study analysing all patients subjected to breast conservative surgery for oncological disease from July 2018 to December 2021. RESULTS: Out of 498 patients enrolled in the study, 253 (50.8%) cases were treated before the pandemic and were designated as "pre-COVID-19" group. The remaining 245 (49.1%) cases were considered the "COVID-19" group. Cases of awake surgery in COVID-19 group were 141 (54.7%) vs. 84 (33.2%), p<0.001. Length of hospitalization and surgical time were comparable between the groups: relative p=0.188 and 0.264, respectively. Differently, operation room occupation was significantly shorter in the COVID-19 group, p<0.001; and number of outpatient surgical procedures was higher, p=0.0304. Multivariate analysis identified the period of surgery (OR=1.47) as a statistically significant factor, p=0.011, predictive of prolonged operatory room occupancy. CONCLUSION: Awake surgery was one of the strategies which made more operating rooms available and allowed avoiding further delays.