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.

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.

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.

The FALD-V: A predictive formula for preoperative volume assessment of adipose tissue transplantation in FALD flap.

BACKGROUND: The fat-augmented latissimus dorsi (FALD) flap is an evolution of the traditional latissimus dorsi (LD) flap, which allows to obtain a total autologous breast reconstruction (BR) avoiding the use of breast implants. The aim of this study was to develop a predictive preoperative formula in order to estimate and optimize the amount of fat to be transferred during FALD flap BR, using only anthropometric measurements. METHODS: We conducted a prospective clinical study between September 2020 and April 2023. All patients underwent back pre-operative ultrasound scan to assess the subcutaneous skin paddle thickness (SPT) and a regression analysis was performed to evaluate which anthropometric variable had a better correlation with this thickness. RESULTS: Data from 66 FALD flaps were collected. The mean SPT was 11.95 mm (SD 4.56). A significant correlation between SPT and body mass index (BMI) was found (r = 0.640, p < 0.0001). Using the fat-to-capacity ratio (113%), the following formula (the FALD-V) was developed to predict the needed fat transfer into FALD flap: [-509 + 12.32 × BMI + 11.71 × skin paddle width + 17.43 × skin paddle height] × 1.13. The considered variables (BMI, skin paddle width and skin paddle height) were statistically significant (p < 0.001, p = 0.0483, p = 0.0154, respectively). The cross-validation confirmed the accuracy of the formula (r = 0.810). CONCLUSION: The FALD-V can be used as an innovative complimentary device in the planning of FALD flap one-stage total autologous BR. To enhance its application, a 3.0 WebApp at www.braflap.com (and www.breast-v.com) is available free of charge for both iOS and Android devices. LEVEL OF EVIDENCE: II.

Exploring the Spectrum of VEGF Inhibitors' Toxicities from Systemic to Intra-Vitreal Usage in Medical Practice.

The use of Vascular Endothelial Growth Factor inhibitors (VEGFi) has become prevalent in the field of medicine, given the high incidence of various pathological conditions necessitating VEGF inhibition within the general population. These conditions encompass a range of advanced neoplasms, such as colorectal cancer, non-small cell lung cancer, renal cancer, ovarian cancer, and others, along with ocular diseases. The utilization of VEGFi is not without potential risks and adverse effects, requiring healthcare providers to be well-prepared for identification and management. VEGFi can be broadly categorized into two groups: antibodies or chimeric proteins that specifically target VEGF (bevacizumab, ramucirumab, aflibercept, ranibizumab, and brolucizumab) and non-selective and selective small molecules (sunitinib, sorafenib, cabozantinib, lenvatinib, regorafenib, etc.) designed to impede intracellular signaling of the VEGF receptor (RTKi, receptor tyrosine kinase inhibitors). The presentation and mechanisms of adverse effects resulting from VEGFi depend primarily on this distinction and the route of drug administration (systemic or intra-vitreal). This review provides a thorough examination of the causes, recognition, management, and preventive strategies for VEGFi toxicities with the goal of offering support to oncologists in both clinical practice and the design of clinical trials.

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.

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.

The Ergonomic FALD Flap for One-stage Total Breast Reconstruction.

Background: The fat-augmented latissimus dorsi (FALD) flap combines this pedicled flap with immediate intraoperative fat transfer. Very little is described concerning its inset at the mammary site. Our efforts have concentrated on seeking the best flap orientation and skin-adipose paddle shaping, to improve the aesthetic outcome and to obtain a complete breast reconstruction (BR) in one stage. Methods: A prospective clinical study was performed in patients who underwent BR with FALD flaps, between December 2020 and March 2022. Patients were randomly enrolled into two groups: ergonomic inset of the FALD flap with vertical orientation of the skin-adipose paddle (group A) and FALD flap with traditional horizontal paddle orientation (group B). The study's endpoints were the evaluation of the aesthetic outcomes (from patients' and surgeon's perspectives) and complications. Results: Thirty-two FALD flaps (23 patients) were performed for group A, and 31 FALD flaps (25 patients) for group B. The two groups were homogeneous in terms of demographic and surgical data (P > 0.05). The overall complication rate was homogeneous among the groups, without statistically significant differences (P = 1.00). The surgeon's assessments showed a statistically significant superior aesthetic outcome in group A regarding volume, symmetry, and shape (P < 0.05). Higher satisfaction was observed in group A patients, in terms of breast size (P < 0.00001), shape (P = 0.0049), and overall satisfaction (P = 0.00061). Conclusions: The ergonomic vertical FALD flap technique enables surgeons to perform one-stage total BR, with excellent breast projection and upper pole fullness. These refinements in flap shaping and molding reduced the need for further autologous fat transfer, obtaining a brilliant totally autologous BR without the need for microsurgical experience.

Blood-Derived Systemic Inflammation Markers and Risk of Nodal Failure in Stage Ia Non-Small Cell Lung Cancer: A Multicentric Study.

BACKGROUND: Unexpected spread to regional lymph nodes can be found in up to 10% of patients with early stage non-small cell lung cancer (NSCLC), thereby affecting both prognosis and treatment. Given the known relation between systemic inflammation and tumor progression, we sought to evaluate whether blood-derived systemic inflammation markers might help to the predict nodal outcome in patients with stage Ia NSCLC. METHODS: Preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation score (SII, platelets × NLR) were collected from 368 patients who underwent curative lung resection for NSCLC. After categorization, inflammatory markers were subjected to logistic regression and time-event analysis in order to find associations with occult nodal spread and postoperative nodal recurrence. RESULTS: No inflammation marker was associated with the risk of occult nodal spread. SII showed a marginal effect on early nodal recurrence at a quasi-significant level (p = 0.065). However, patients with T1c tumors and elevated PLR and/or SII had significantly shorter times to nodal recurrence compared to T1a/T1b patients (p = 0.001), while patients with T1c and normal PLR/SII did not (p = 0.128). CONCLUSIONS: blood-derived inflammation markers had no value in the preoperative prediction of nodal status. Nevertheless, our results might suggest a modulating effect of platelet-derived inflammation markers on nodal progression after the resection of tumors larger than 2 cm.

Narrow inferior-central septum-based pedicle: A safe technique to improve aesthetic outcomes in breast reduction.

BACKGROUND: Inferior-central pedicle has some aesthetic drawbacks, including hypertrophic scar along the inframammary fold (IMF), squaring of the breast contours, and propensity to develop long-term 'bottoming-out.' This study aimed to verify if the narrow inferior-central (NIC) septum-based pedicle can allow the surgeon to improve aesthetic outcomes compared with the traditional inferior-central pedicle approach. METHODS: Forty breasts underwent NIC-based breast reduction (group A), and 37 underwent traditional inferior-central pedicles (group B). The NIC pedicle was drawn with a width of 3.5-4.5 cm. The recorded measurements were sternal notch to nipple distance (S-N) and nipple to IMF distance (N-IMF) at the time of preoperative markings and follow-up 1, 6, and 18 months after the procedure. RESULTS: The two groups were homogeneous regarding demographics, operative data, and preoperative S-N and N-IMF distances. Both groups showed no total or partial nipple-areola necrosis. At the 18-month follow-up, S-N (p < 0.00001) and N-IMF (p = 0.00039) distances were statistically different between the two groups, in favour of NIC group A. Changes in N-IMF distances between the 1- and 18-month visits were statistically different among groups (p < 0.0001), with a length variation of + 17.51% and + 28.46%, respectively. Patient satisfaction rate regarding "breast shape" (p = 0.021), "lower pole appearance" (p = 0.00017), and "scar" (p = 0.047) were higher in group A. CONCLUSION: NIC-based pedicle proved to be a safe procedure and allowed us to overcome limitations that typically characterise the inferior pedicle, i.e., 'bottoming-out' deformity, hypertrophic scar of the lower pole, and squaring of the breast contours. LEVEL OF EVIDENCE: II.

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.

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.

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.

Fat-Augmented Latissimus Dorsi Flap for Secondary Breast Reconstruction in Small to Medium-Sized Irradiated Breasts.

BACKGROUND: Secondary breast reconstruction (BR) is recognized as a challenging procedure, particularly when radiotherapy (RT) has previously been performed. The aim of this study was to compare operative data and aesthetic outcomes between secondary irradiated and immediate BR using the fat-augmented latissimus dorsi (FALD) flap. METHODS: The authors conducted a prospective clinical study between September of 2020 and September of 2021. Patients were divided into two groups: group A included secondary BR using the FALD flap in previously irradiated breasts, and group B included immediate BR with the FALD flap. Demographics and surgical data were compared, and an aesthetic analysis was performed. Chi-square and t tests were performed for categorical and continuous variables, respectively. RESULTS: Twenty cases of FALD flap-based BR for each group were included. The two groups were found to be homogeneous for the demographic variables. The difference in mean operative time (263.1 minutes versus 265.1 minutes; P = 0.467) and complications ( P = 0.633) between the two groups were not significant. There was statistically significant difference in term of immediate fat grafting volume in favor of group A (218.2 cc versus 133.0 cc; P < 0.0001). Regarding aesthetic outcomes, the mean global score evaluation showed no statistically significant differences between groups (17.86 versus 18.21; P = 0.209). CONCLUSIONS: The authors' study states that the FALD flap can be considered a reliable procedure for secondary reconstruction in previously irradiated breasts, although it is not indicated for patients with larger breasts. This surgical technique allowed us to achieve a totally autologous BR with good aesthetic results and low complication rates, even in secondary irradiated cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

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.

Quantification of Extracellular Volume in CT in Neoadjuvant Chemotherapy in Breast Cancer: New Frontiers in Assessing the Cardiotoxicity of Anthracyclines and Trastuzumab.

Breast cancer patients undergoing neoadjuvant chemotherapy with anthracyclines or trastuzumab can suffer cardiotoxic issues. Nowadays, the markers of cardiac damage are still not reliable, and extracellular volume (ECV) calculated from CT could be a promising cardiotoxic marker. Eighty-two patients, treated with two different chemotherapy regimens based on doxorubicin (DOX) or epirubicin-trastuzumab (EPI-TRAS), were retrospectively selected and the variations in extracellular volume (ECV) values were measured and analyzed. Whole Body CT (WB-CT) scans were acquired after 1 min, in the portal phase (PP), and after 5 min, in the delayed phases (DP), at the baseline (T0), after one year (T1) and after five years (T5) from the end of chemotherapies. The values measured by two radiologists with different levels of experience were evaluated in order to assess the inter-reader reproducibility assessment (ICC = 0.52 for PP and DP). Further, we performed a population-based analysis and a drug-oriented subgroup analysis in 54 DOX-treated and 28 EPI-TRAS-treated patients. In the general cohort of women treated with any of the two drugs, we observed in the lapse T0-T1 a relative increase (RI) of 25% vs. 20% (PP vs. DP, p < 0.001) as well as in the lapse T0-T5 an RI of 17% vs. 15% (PP vs. DP, p < 0.01). The DOX-treated patients reported in the lapse T0-T1 an RI of 22% (p < 0.0001) in PP and an RI of 16% (p = 0.018) in the DP, with ECV values remaining stably high at T5 both in PP (RI 14.0%, p < 0.0001) and in DP (RI 17%, p = 0.005) highlighting a possible hallmark of a persisting CTX sub-damage. On the other hand, ECV measured in EPI-TRAS-treated women showed an RI in T0-T1 of 18% (p = 0.001) and 29% (p = 0.006) in PP and DP, respectively, but the values returned to basal levels in T5 both in the PP (p = 0.12) and in DP setting (p = 0.13), suggesting damage in the first-year post-treatment and a possible recovery over time. For the 82 patients, an echocardiography was performed at T0, T1= 12 m + 3 m and T5 = 60 m + 6 m with LVEF values at T0 (64% ± 5%), T1 (54% ± 6%) and T5 (53% ± 8%). WB-CT-derived ECV values could provide a valid imaging marker for the early diagnosis of cardiotoxic damage in BC patients undergoing oncological treatments. We detected different patterns during the follow-up, with stably high values for DOX, whereas EPI-TRAS showed a peak within the first year, suggesting different mechanisms of cardiac damage.

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.