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Objectives. The aim of this prospective phase II study is to evaluate the treatment of early-stage breast cancer (T1 N0) with intraoperative electron radiation therapy (IOERT) in terms of local control, early complications, and cosmesis. Patients and Methods. From February 2010 to February 2012, 200 patients underwent partial IOERT of the breast. Inclusion criteria were unifocal invasive ductal carcinoma, age ≥40 years, histological tumour size ≤20 mm, and no lymph node involvement. A 21 Gy dose was prescribed over the 90% isodose line in the tumour bed. Median follow-up is 23.3 months (7–37). Results. Acute toxicity was not frequent (Grade 1: 4.5%, Grade 2: 1%). The cosmetic result was considered to be very good or good in 92.5%. One ipsi lateral out-quadrant recurrence at 18 months was observed. The crude and actuarial local recurrence rates after median follow-up were 0.5% and 0.9%, respectively. Conclusion. The preoperative diagnostic work-up must be comprehensive and the selection process must be rigorous for this therapeutic approach reserved for small ductal unifocal cancers. After a 23.3-month median follow-up time, the clinical results of IOERT for selected patients are encouraging for the locoregional recurrence and the toxicity rates. The satisfaction of our patients in terms of quality of life was extremely high.

Background: This review summarizes the available data on the effectiveness of indocyanine green fluorescence imaging (ICG-FI) for real-time detection of breast cancer (BC) tumors with perioperative imaging technologies., Methods: PubMed and Scopus databases were exhaustively searched for publications on the use of the real-time ICG-FI evaluation of BC tumors with non-conventional breast imaging technologies., Results: Twenty-three studies were included in this review. ICG-FI has been used for BC tumor identification in 12 orthotopic animal tumor experiences, 4 studies on animal assessment, and for 7 human clinical applications. The BC tumor-to-background ratio (TBR) was 1.1-8.5 in orthotopic tumor models and 1.4-3.9 in animal experiences. The detection of primary human BC tumors varied from 40% to 100%. The mean TBR reported for human BC varied from 2.1 to 3.7. In two studies evaluating BC surgical margins, good sensitivity (93.3% and 100%) and specificity (60% and 96%) have been reported, with a negative predictive value of ICG-FI to predict margin involvement intraoperatively of 100% in one study., Conclusions: The use of ICG-FI as a guiding tool for the real-time identification of BC tumors and for the assessment of tumor boundaries is promising. There is great variability between the studies with regard to timing and dose. Further evidence is needed to assess whether ICG-guided BC surgery may be implemented as a standard of care., (© 2024. The Author(s).)

Background: The most common mode of ovarian cancer (OC) spread is intraperitoneal dissemination, with the peritoneum as the primary site of metastasis. Cytoreductive surgery (CRS) with chemotherapy is the primary treatment. When necessary, a digestive resection can be performed, but the role of mesenteric lymph nodes (MLNs) in advanced OC remains unclear, and its significance in treatment and follow-up evaluation remains to be determined. This study aimed to evaluate the prevalence of MLN involvement in patients who underwent digestive resection for OC peritoneal metastases (PM) and to investigate its potential prognostic value., Methods: This retrospective, descriptive study included patients who underwent CRS with curative intent for OC with PM between 1 January 2007 and 31 December 2020. The study assessed MLN status and other clinicopathologic features to determine their prognostic value in relation to overall survival (OS) and progression-free survival (PFS)., Results: The study enrolled 159 women with advanced OC, 77 (48.4%) of whom had a digestive resection. For 61.1% of the patients who underwent digestive resection, MLNs were examined and found to be positive in 56.8%. No statistically significant associations were found between MLN status and OS (p = 0.497) or PFS ((p = 0.659)., Conclusions: In anatomopathologic studies, MLNs are not systematically investigated but are frequently involved. In the current study, no statistically significant associations were found between MLN status and OS or PFS. Further prospective studies with a systematic and standardized approach should be performed to confirm these findings., (© 2023. The Author(s).)

Background: Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in., Methods: The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2-6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery., Results: Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37-69. All patients received SBRT and underwent surgery 2-4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4-5 AE were documented. Overall cosmetical breast evaluation after surgery was 'excellent' in four patients and 'good' in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3., Conclusions: This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial., Trial Registration Number: NCT03875573., Competing Interests: Competing interests: ADC: institutional, AstraZeneca. ER: institutional, BMS; institutional: AstraZeneca; institutional: Replimune. Research fundings: Fondation Amgen, Fondation BMS; travel grant from Roche, BMS, Merck. Research fundings: Amgen. AG: Financial Interests, Institutional, AstraZeneca; Financial Interests, Institutional: Daiichi. EA: Consultancy fees/honoraria: Eli Lilly, Sandoz, AstraZeneca. Institutional: Gilead. Support for attending medical conferences from: Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo, AstraZeneca. DVG: Advisory board/Honoraria received: Sanofi, Accuray, Merck-Pfizer, Takeda and Novartis. MP: Board Member (Scientific Board): Oncolytics; Consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Periphagen, Pfizer, Roche, Seattle Genetics. Research grants to my Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genetech, Servier, Synthon. No stock ownership. DVG: Advisory board/Honoraria received: Sanofi, Accuray, Merck-Pfizer, Takeda and Novartis. RS: non-financial support from Merck, non-financial support from BMS, other from Puma Biotechnology, other from Roche, other from Roche, other from Merck. CS: Institutional: Astellas; Personal: Cepheid; Institutional: Vertex; Institutional: Seattle Genetics; Personal: Puma; Institutional: AMGEN; Personal: Eisai; Institutional, Other, Travel: Roche; Institutional, Other, Internal speaker: Genentech; Personal, Other, Regional speaker: Pfizer; Institutional: Inc.; Institutional: Exact Sciences; Institutional: Merck & Co; Personal: prIME Oncology, Personal: Teva. MP: Board Member (Scientific Board): Oncolytics; Consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Periphagen, Pfizer, Roche, Seattle Genetics. Research grants to my Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genetech, Servier, Synthon. No stock ownership. MI: Consultant or advisory role (honoraria): Celgene, Novartis, Pfizer, Seattle Genetics, Tesaro. Research grants to my Institute: Roche, Menarini Silicon Biosystems, Janssen Diagnostics, Pfizer. No stock ownership. Travel grants: Pfizer, Amgen. LB: institutional research grant from AstraZeneca; speaker honoraria from BMS, Novartis; travel grant from Roche, GILEAD. Advisory Board: Iteos, Domain Therapeutics. All other authors: no disclosures., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Sentinel lymph node biopsy (SLNB) represents the gold standard for axillary surgical staging. The aim of this study was to assess the proportion of axillary lymph node dissection (ALND) that could be avoided after retrospective application of the ACOSOG Z0011 criteria and to evaluate the shortterm complications associated with axillary surgery., Materials and Methods: We reviewed breast cancer (BC) patients treated by primary breast-conserving surgery from 2012 to 2015. The percentage of SLNB vs ALND performed before and after the application of the ACOSOG Z0011 criteria was calculated. Complications were analyzed using crosstabs, with p <0.05 considered significant., Results: Two hundred fifty one patients with a median age of 59.3 years were included. BC tumors had a median size of 13 mm and were mostly unifocal (83.9%). There were 30.3% with 1-2 metastatic lymph nodes (MLN). ALND was performed in 44.2%. The patients with 1-2 MLN, had only SLNB in 14.5% of cases. By applying the ACOSOG Z0011 criteria, ALND would have been avoided in 40.2% of patients. At least one postoperative complication was reported after SLNB or ALND for 45.7% and 74.7% of patients respectively. Seroma was the most frequent complication, and occurred in 29.3% of cases after SLNB and in 59.5% after ALND., Conclusion: SNLB is the most commonly used axillary surgical staging procedure in this series (55.8%). With a retrospective application of the ACOSOG Z0011 criteria in our population, ALND could have been avoided for 40.2% patients. Post-operative complications rate was higher after ALND, with a seroma rate at 59.5%., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

Introduction: Although complete cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) offers a good prognosis in patients with peritoneal metastasis of ovarian cancer (PMOC), recurrences are quite common. These recurrences can be intra-abdominal or systemic in nature. Our objective was to study and illustrate the global recurrence pattern in patients operated for PMOC, shedding light on a previously overlooked lymphatic basin at the level of the epigastric artery, the deep epigastric lymph nodes (DELN) basin., Patients and Methods: This was a retrospective study including patients with PMOC who underwent surgery with curative-intent, from 2012 until 2018, at our cancer center, and who presented with any type of disease recurrence on follow-up. CT-scans, MRIs and PET-scans were reviewed in order to determine solid organs and lymph nodes (LN) recurrences., Results: During the study period, 208 patients underwent CRS ± HIPEC, 115 (55.3%) presented with organ or lymphatic recurrence over a median follow-up of 81 months. Sixty percent of these patients had radiologically enlarged LN involvement. The pelvis/pelvic peritoneum was the most common intra-abdominal organ recurrence site (47%), while the retroperitoneal LN was the most common lymphatic recurrence site (73.9%). Previously overlooked DELN were found in 12 patients, with 17.4% implication in lymphatic basin recurrence patterns., Conclusion: Our study revealed the potential role of the DELN basin, previously overlooked in the systemic dissemination process of PMOC. This study sheds light on a previously unrecognized lymphatic pathway, as an intermediate checkpoint or relay, between the peritoneum, an intra-abdominal organ, and the extra-abdominal compartment., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any "peritoneal scar-like tissues" (PST) during CRS, hasn't been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC., Methods: This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients' variables, were studied., Results: In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group (p = 0.05), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS., Conclusion: Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The final oncological and aesthetic results of breast-conserving surgery (BCS) are influenced by the precise localization of breast cancer (BC) tumors and by the quality of the intraoperative margin assessment technique. This study aimed to assess the effectiveness of the carbon localization (CL) technique by determining the success rate of BC identification and the proportion of adequate complete resection of BC lesions., Methods: We conducted a cross-sectional retrospective study of patients treated with primary BCS for invasive BC who underwent CL of their BC lesion at the Jules Bordet Institute between January 2015 and December 2017. Descriptive statistics with categorical and continuous variables were used. The success rate of tumor identification and the rate of adequate excision were calculated using the test of percentages for independent dichotomous data., Results: This study included 542 patients with 564 nonpalpable BC lesions. The median pathological tumor size was 12 mm. Of these, 460 were invasive ductal carcinomas. Most of the tumors were of the luminal subtype. CL was performed using ultrasound guidance in 98.5% of cases. The median delay between CL and surgery was 5 days, with 46% of the patients having CL one day before surgery. The lumpectomy weighed 38 g on average, with a median diameter of the surgical sample at 6 cm and a median volume of 44 cm 3 (6-369). One-stage complete resection was successfully performed in 93.4% of cases. In 36% of cases, an intraoperative re-excision was performed, based on intraoperative macroscopic pathological margin evaluation. The tumor was identified in 98.9% of cases in the breast surgical specimen., Conclusion: This study demonstrated high success rates for BC tumor identification (99%) and one-stage complete resection (93.4%) after BCS and CL. These results show that CL is an effective, simple, and inexpensive localization technique for successful excision of BC lesions during BCS., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Etienne El-Helou et al.)

Objectives: Peritoneal metastases of ovarian cancer (PMOC) are common at initial presentation. Cytoreductive surgery (CRS) of curative intent has been proven to be efficient in increasing the overall survival (OS) and the disease-free survival (DFS) of these patients. Nevertheless, CRS is associated with high postoperative morbidity, which makes patient selection a major concern. Appropriate prognostic factors that can predict patient outcomes after surgery are still lacking. Preoperative biomarkers and their ratios have been shown to be predictive of patient prognosis for various solid tumors. We aimed to study their correlation with the prognosis of patients undergoing CRS for PMOC., Methods: This retrospective study included patients with PMOC operated by CRS. Preoperative biomarkers and other clinicopathological characteristics were studied to determine their prognostic value in terms OS and DFS., Results: 216 patients were included. Patients with preoperative hemoglobin (Hb) <11.7 g/dL had a poorer prognosis in terms of OS (p=0.0062) and DFS (p=0.0077). Additionally, increased neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) >0.32, and platelet-to-lymphocyte ratio (PLR) >214.5 were associated with worse OS (p=0.022, p=0.0028, and p=0.0018, respectively) and worse DFS (p=0.028, p=0.003, and p=0.019, respectively). Multivariate analysis showed that the variables mentioned above were independent predictive factors for OS and DFS., Conclusions: Preoperative Hb level, NLR, MLR, and PLR are prognostic factors for OS and DFS in PMOC patients operated by curative CRS., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Uterine embryonal rhabdomyosarcoma (uERMS) in adult women is a very rare malignant entity. The study aim was to report a case of adult uERMS and to discuss the implications of histopathological diagnosis on the treatment and prognosis., Case Presentation: We present here the clinicopathological features of a uERMS case in an adult woman. The study has been approved by the institutional Ethics Committee and an informed consent has been obtained (IJB∕CE3005). A 45-year-old woman presented to her gynecologist with intermenstrual bleedings and polypoid cervical mass (initially interpreted as benign polyp). A second biopsy was sent to our Department of Pathology at the Jules Bordet Institute, Brussels, Belgium for revision and was reinterpreted as botryoid-type uERMS. The patient underwent a total hysterectomy. The final pathology confirms a 3 cm cervical ERMS, and a simple surveillance was decided by our multidisciplinary team. Six months later, pelvic magnetic resonance imaging control showed a recurrence in the right pelvic lymph nodes. Multi-drug chemotherapy and radiotherapy were done before surgical resection. Pathological examination of the resected pelvic mass confirmed uERMS recurrence of 60 mm, with large zones of necrosis and the presence of cartilaginous structures. The patient is free of disease 60 months after diagnosis., Conclusions: Adult uERMS is rare and the pathological examination is the main element for diagnosis and treatment. It is often confused with other benign entities, at least at the time of diagnosis. ERMS should be included in the differential diagnosis of cervical and uterine polyp of adult women. Long-term survival is possible with a multimodal therapy approach.

Background: Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial., Methods: At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical)., Results: Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%., Conclusions: The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk., (© 2022. The Author(s).)

Solitary fibrous tumor (SFT) of the breast is a rare mesenchymal tumor composed of spindle-shaped tumor cells with collagen and large blood vessels in the shape of a "staghorn". It is discovered anywhere in the human body, usually incidentally or through nonspecific symptoms. A combination of clinical, histological, and immunohistochemical features is required to establish a diagnosis. There are no proper guidelines for the treatment of SFTs because of their rarity; however, wide surgical excision remains the "gold standard". A multidisciplinary team approach is recommended. They are mostly benign with a 5-year survival rate of 89%. Following a PubMed-indexed English literature review, only six publications presenting nine cases of breast SFT in a male patient were found. The following is the case of a 73-year-old man who presented with dry cough. A SFT in the right breast was discovered incidentally during the investigative work up, and the patient was referred to our Breast Clinic at the Jules Bordet Institute, Brussels, Belgium, for appropriate treatment. The patient's presentation, imaging, and histological sample all supported the diagnosis, and he underwent uneventful surgical resection. Here, we present the first case of an incidental finding of a SFT of the male breast, with its diagnosis and therapeutic challenges.

Purpose: Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy in patients with early-stage breast cancer may allow for early detection of relapse. In this study, we analyzed ctDNA using a personalized, tumor-informed multiplex polymerase chain reaction-based next-generation sequencing assay., Methods: Plasma samples (n = 157) from 44 patients were collected before neoadjuvant therapy (baseline), after neoadjuvant therapy and before surgery (presurgery), and serially postsurgery including a last follow-up sample. The primary end point was event-free survival (EFS) analyzed using Cox regression models., Results: Thirty-eight (86%), 41 (93%), and 38 (86%) patients had baseline, presurgical, and last follow-up samples, respectively. Twenty patients had hormone receptor-positive/human epidermal growth factor receptor 2-negative, 13 had triple-negative breast cancer, and 11 had human epidermal growth factor receptor 2-positive disease. Baseline ctDNA detection was observed in 22/38 (58%) patients and was significantly associated with Ki67 > 20% ( P = .036) and MYC copy-number gain ( P = .0025, false discovery rate = 0.036). ctDNA detection at presurgery and at last follow-up was observed in 2/41 (5%) and 2/38 (5%) patients, respectively. Eight relapses (seven distant and one local) were noted (median follow-up 3.03 years [range, 0.39-5.85 years]). After adjusting for pathologic complete response (pCR), ctDNA detection at presurgery and at last follow-up was associated with shorter EFS (hazard ratio [HR], 53; 95% CI, 4.5 to 624; P < .01, and HR, 31; 95% CI, 2.7 to 352; P < .01, respectively). Association between baseline detection and EFS was not observed (HR, 1.4; 95% CI, 0.3 to 5.9; P = .67)., Conclusion: The presence of ctDNA after neoadjuvant chemotherapy is associated with relapse in early-stage breast cancer, supporting interventional trials for testing the clinical utility of ctDNA monitoring in this setting., Competing Interests: Elisa AgostinettoHonoraria: Lilly, SandozTravel, Accommodations, Expenses: Novartis, Genetic Matteo LambertiniConsulting or Advisory Role: Roche, Novartis, Lilly, AstraZeneca, Pfizer, MSD, Exact Sciences, Gilead Sciences, Seattle GeneticsSpeakers' Bureau: Takeda, Roche, Lilly, Novartis, Pfizer, Sandoz, Ipsen, Knight Therapeutics, LibbsTravel, Accommodations, Expenses: Gilead Sciences Hsin-Ta WuEmployment: NateraStock and Other Ownership Interests: NateraTravel, Accommodations, Expenses: Natera Mustafa BalciogluEmployment: NateraStock and Other Ownership Interests: Natera Ekaterina KalashnikovaEmployment: NateraStock and Other Ownership Interests: NateraTravel, Accommodations, Expenses: Natera Andrea GombosConsulting or Advisory Role: AstraZeneca (Inst)Travel, Accommodations, Expenses: Pfizer Ahmad AwadaConsulting or Advisory Role: Roche, Lilly, Amgen, Eisai, Bristol Myers Squibb, Pfizer, Novartis, MSD, Genomic Health, Ipsen, AstraZeneca, Bayer, LEO Pharma, Merck Serono, Daiichi Sankyo/Lilly, Pierre Fabre, Seattle Genetics, Hengrui Therapeutics, Innate Pharma Himanshu SethiEmployment: NateraStock and Other Ownership Interests: NateraResearch Funding: NateraPatents, Royalties, Other Intellectual Property: PatentsTravel, Accommodations, Expenses: Natera Alexey AleshinEmployment: NateraLeadership: NateraStock and Other Ownership Interests: NateraConsulting or Advisory Role: Mission BioTravel, Accommodations, Expenses: Natera Christos SotiriouConsulting or Advisory Role: Astellas Pharma, Cepheid, Vertex, Puma Biotechnology, Seattle Genetics, Amgen, MerckSpeakers' Bureau: Eisai, Prime Oncology, Teva, Foundation Medicine, Genmic HealthPatents, Royalties, Other Intellectual Property: Epigenetic portraits of human Breast Cancer, PCT/EP2012/050836, WO2012/098215, A companion diagnostic for CDK4/CDK6 inhibitory drugs based on CDK4 Phosphorylation. Which patient to be treated and how. PCT/EP2017/061780Travel, Accommodations, Expenses: Roche, Roche/Genentech Michail IgnatiadisConsulting or Advisory Role: Seattle Genetics, NovartisResearch Funding: Roche/Genentech (Inst), Pfizer (Inst), Natera (Inst)Patents, Royalties, Other Intellectual Property: Patent entitled method for determining sensitivity to a CDK4/6 inh filed the 18 05 16 by Universite Libre de Bruxelles, Application No/Patent No 16170146.1-1403Travel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Background: Axillary web syndrome (AWS) is a frequent complication after surgery for breast cancer, but its lymphatic involvement is not definitively established. Here we report the results of lymphoscintigraphic investigations in patients with AWS. Methods and Results: We conducted a retrospective, single-center review of lymphoscintigraphic investigations performed in 46 patients with AWS that was either clinically obvious or suspected. Of this group, 23 patients had two investigations with a mean interval of 19 weeks between them (range, 6-98 weeks). Results of the lymphoscintigraphic investigations, which were performed according to a well-standardized protocol, were classified into four patterns: normal; functional lymphatic insufficiency only (no lymphatic vascular morphologic abnormality); lymphovascular blockade without collateralization; and vascular collateralization and/or dermal backflow. Of the 46 patients, on the first lymphoscintigraphic investigation, four (8.6%) had a normal pattern, seven (15.2%) had functional lymphatic insufficiency only, four (8.6%) had lymphovascular blockade without collateralization, and 31 (67.3%) had vascular collateralization and/or dermal backflow. Among patients who underwent two investigations, four of the five who had only functional lymphatic insufficiency at the first investigation had developed vascular collateralization and/or dermal backflow by the second. The three patients who had lymphovascular blockade without collateralization at the first examination had also progressed to collateralization and/or dermal backflow at the second. None of the 15 patients who initially had vascular collateralization and/or dermal backflow showed any reversal at the second examination. Conclusions: Our analysis confirms the lymphatic nature of AWS and shows the lymphoscintigraphic patterns and evolutions of the lymphatic lesions with potential therapeutic implications. The retrospective review of our database is approved by the institutional ethics committee under number 2048.

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

ICG with other tracers can be injected pre and/or per operatively to identify the axillary Lymph Nodes (LN) draining the breast cancer (the SLN nodes) and/or the ipsilateral arm (the ARM nodes). to evaluate the impact on this temporal variable-variation on the identification of these ARM LN. Material and methods: One hundred and nine women, who were scheduled to undergo, either lumpectomy with selective lymphadenectomy (SLN), or mammary surgery (either lumpectomy, or mastectomy) with complete axillary node dissection (CALND) for a histologically proven mammary tumor, had administered the day before the surgery one subcutaneous injection of ICG in the first interdigital space of the ipsilateral hand (pre-op subgroup (SLN=28 and CALND=15), or the same day as the surgery (per op subgroup (SLN=26 and CALND= 20). The fluorescent characteristics of the SLN and/or axillary LN were then analyzed and compared between the two subgroups. Results: Basic characteristics were not significantly different between the pre and per op subgroups. The percentage of patients found with fluorescent SLN (28%), the percentage of patients with fluorescent LN in CALND (74.5%), or the percentage of LN fluorescent in CALND (38.5%) did not differ significantly too. Conclusion: Injection of ICG in the first interdigital space of the hand of operated side performed one day before the surgery or the same day as the surgery has no significant influence in our study on detection of the arm nodes. The timing of ICG injection is an independent variable with no effect on the results; this allows the injection to be performed either the day before the surgery or the day of the surgery., (Celsius.)

Background: Near-infrared fluorescence imaging (NIRFI) of breast cancer (BC) after the intravenous (IV) injection of free indocyanine green (fICG) has been reported to be feasible. However, some questions remained unclarified., Objective: To evaluate the distribution of fICG in BC and the axillary lymph nodes (LNs) of women undergoing surgery with complete axillary LN dissection (CALND) and/or selective lymphadenectomy (SLN) of sentinel LNs (NCT no. 01993576 and NCT no. 02027818)., Methods: An intravenous injection of fICG (0.25 mg/kg) was administered to one series of 20 women undergoing treatment with mastectomy, the day before surgery in 5 (group 1) and immediately before surgery in 15 (group 2: tumor localization, 25; and pN+ CALND, 4) as well as to another series of 20 women undergoing treatment with tumorectomy (group 3). A dedicated NIR camera was used for ex vivo fluorescence imaging of the 45 BC lesions and the LNs., Results: In group 1, two of the four BC lesions and one large pN+ LN exhibited fluorescence. In contrast, 24 of the 25 tumors in group 2 and all of the tumors in group 3 were fluorescent. The sentinel LNs were all fluorescent, as well as some of the LNs in all CALND specimens. Metastatic cells were found in the fluorescent LNs of the pN+ cases. Fluorescent BC lesions could be identified ex vivo on the surface of the lumpectomy specimen in 14 of 19 cases., Conclusions: When fICG is injected intravenously just before surgery, BC can be detected using NIRFI with high sensitivity, with metastatic axillary LNs also showing fluorescence. Such a technical approach seems promising in the management of BC and merits further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bourgeois, Veys, Noterman, De Neubourg, Chintinne, Vankerckhove and Nogaret.)

Introduction: Positive margins after breast-conserving surgery (BCS) for breast cancer (BC) remain a major concern. In this study we investigate the feasibility and accuracy of indocyanine green (ICG) fluorescence imaging (FI) for the in vivo assessment of surgical margins during BCS., Materials and Methods: Patients with BC admitted for BCS from October 2015 to April 2016 were proposed to be included in the present study (NCT02027818). ICG (0.25 mg/kg) was intravenously injected at induction anesthesia and ICG-FI of the surgical beds was correlated with final pathology results., Results: Fifty patients consented to participate and thirty-five patients were retained for final analysis, 15 patients having been excluded for, respectively, incomplete video records data for signal to background ratio (SBR) calculation (11) and in situ tumors (4). The final pathological assessment of 35 breast specimens identified 5 (14.7%) positive margins. Intraoperative ICG-FI revealed hyperfluorescent signals in 15 (42.9%) patients and an absence of fluorescent signals in 20 (57.1%). Median SBR in patients with involved margins was 1.8 (SD 0.7) and was 1.25 (SD 0.6) in patients with clear margins (p = 0.05). The accuracy, specificity, positive and negative predictive value of ICG-FI for breast surgical margin assessment were 71%, 60%, 29% and 100%, respectively., Conclusion: ICG-FI of BC surgical beds has a high negative predictive value for surgical margin assessment during BCS. The absence of residual fluorescence in the surgical bed of patients with fluorescent tumors predicts negative margins at final pathology and allows the surgeon to avoid further intraoperative analysis., (Copyright © 2020. Published by Elsevier Ltd.)

Background and Objectives: We report, for the first time in the literature, a metastatic lymphatic pathway along the inferior epigastric vessels, through the inferior epigastric lymph nodes (IELNs), in patients with peritoneal carcinomatosis (PC). Interestingly, these lymph nodes (LNs) in the anterior retroperitoneum were not detectable on preoperative imaging. They may, however, represent a pertinent systemic dissemination pathway for PC., Patients and Methods: In patients undergoing indocyanine green-fluorescence imaging during cytoreductive surgery for PC, an incidental finding of a hyperfluorescent LN, harboring metastatic tumorous cells, around the inferior epigastric artery was made., Results: In three out of five patients with clear fluorescent hotspot, the harvested LN was harboring metastatic cancerous cells. None of these nodes, whether negative or positive, was visible on any preoperative imaging modalities. A protocol to sample, in a systematic manner, the IELN in patients with PC, is currently being devised at our institution., Conclusion: These lymphatic nodes basin and channels might reveal to be a potential passage from peritoneal metastasis to the extraperitoneal lymphatic compartment, representing an independent pathway for cancerous cell dissemination. This will bring us to further investigate the prevalence and the prognostic significance of these LNs., (© 2020 Wiley Periodicals LLC.)

Introduction: Cytoreductive surgery of locally advanced ovarian cancer has evolved in the last few years from surgery to remove macroscopic residual disease (<1cm; R2b) to macroscopic complete cytoreductive surgery with no gross residual disease (R1). The aim of this study was to evaluate the impact of the adoption of a maximalist surgical approach on postoperative complications, disease recurrence and survival., Materials and Methods: This was a retrospective study using prospectively collected data on patients who received either conservative approach (CA) or radical approach (RA) surgical treatment for primary ovarian cancer stage IIIc/IVa/IVb between June 2006 and June 2013., Results: Data for 114 patients were included, 33 patients in the CA group and 68 patients in the RA group were consequently analysed. In the RA group, operative time was longer, in relation to more complex surgical procedures; with more blood losses and a higher rate of compete macroscopic resection. Totally, 77% of the patients had postoperative complications, with more grade I/II complications in the RA group but the same rates of grade III/IV complications in the both groups (P=0.14). For all patient study population, the overall and disease-free survivals were improved in case of no macroscopic residual disease. Overall survival was improved in the RA group (P=0.05), with no difference in terms of disease-free survival (P=0.29) CONCLUSION: A radical approach in advanced ovarian cancer allows a higher rate of complete cytoreductive surgery impacting overall survival. However, a non-significant trend for increased mild complications (grade I/II) rate is observed in this group., (Copyright © 2019. Published by Elsevier Masson SAS.)

Tumor-infiltrating B-cells (TIL-B) in breast cancer (BC) have previously been associated with improved clinical outcomes; however, their role(s) in tumor immunity is not currently well known. This study confirms and extends the correlation between higher TIL-B densities and positive outcomes through an analysis of HER2-positive and triple-negative BC patients from the BIG 02-98 clinical trial (10yr mean follow-up). Fresh tissue analyses identify an increase in TIL-B density in untreated primary BC compared to normal breast tissues, which is associated with global, CD4+ and CD8+ TIL, higher tumor grades, higher proliferation and hormone receptor negativity. All B-cell differentiation stages are detectable but significant increases in memory TIL-B are consistently present. BC with higher infiltrates are specifically characterized by germinal center TIL-B, which in turn are correlated with TFH TIL and antibody-secreting TIL-B principally located in tertiary lymphoid structures. Some TIL-B also interact directly with tumor cells. Functional analyses reveal TIL-B are responsive to BCR stimulation ex vivo, express activation markers and produce cytokines and immunoglobulins despite reduced expression of the antigen-presenting molecules HLA-DR and CD40. Overall, these data support the concept that ongoing humoral immune responses are generated by TIL-B and help to generate effective anti-tumor immunity at the tumor site.

Although invasive ductal breast cancer (IDC) represents the most common histological type of breast cancer, minor subtypes exist such as mucinous breast cancer (MuBC). MuBC are distinguished by tumor cells floating in extracellular mucin. MuBC patients are generally older and associated with a favorable prognosis. To unravel the molecular architecture of MuBC, we applied low-pass whole-genome sequencing and microscopic evaluation of stromal tumor infiltrating lymphocytes to 30 MuBC from a retrospective institutional cohort. We further analyzed two independent datasets from the International Cancer Genomics Consortium and The Cancer Genome Atlas. Genomic data (n = 26 MuBC, n = 535 estrogen receptor [ER] positive/HER2-negative IDC), methylation data (n = 28 MuBC, n = 529 ER-positive/HER2-negative IDC), and transcriptomic data (n = 27 MuBC, n = 467 ER-positive/HER2-negative IDC) were analyzed. MuBC was characterized by low tumor infiltrating lymphocyte levels (median = 0.0%, average = 3.4%, 95% confidence interval = 1.9% to 4.9%). Compared with IDC, MuBC had a lower genomic instability (P = .01, two-sided Mann-Whitney U test) and a decreased prevalence of PIK3CA mutations (39.7% in IDC vs 6.7% in MuBC, P = .01 in the International Cancer Genomics Consortium; and 34.8% vs 0.0%, P = .02 in The Cancer Genome Atlas, two-sided Fisher's exact test). Finally, our report identifies aberrant DNA methylation of MUC2 as a possible cause of extracellular production of mucin in MuBC., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objectives: The aim of this study was to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the ex vivo detection of metastatic lymph nodes (LNs) in advanced stage ovarian cancer (AOC)., Methods: Paraffin-embedded LNs from patients included in a previous ICG-FI study (Protocol NCT01834469) were further assessed for fluorescence. Intravenous injection of ICG was delivered intraoperatively. Tumor-to-background ratios (TBRs) were calculated., Results: A total of 675 LNs from 19 patients were analyzed. The mean LN number per patient was 29.3 (median: 24; range 2-77). Seventy-three LNs were malignant (10.8%), 602 were benign (89.2%). The mean TBR of all LNs was 1.5 (SD 0.8). With a cut-off TBR of 1.3, the sensitivity, specificity, positive predictive, and negative predictive values of ICG-FI for retroperitoneal LNs were 80%, 41%, 2.8%, and 99%, respectively. On univariate analysis, only the fluorescence ratio (TBR ≥ 1.3) was correlated with malignancy at pathology (P = 0.03). No predictive factors of pathological LN status were found on multivariate analysis., Conclusions: Ex vivo ICG-FI of retroperitoneal LNs in AOC had good sensitivity but poor specificity. However, its high negative predictive value could make it an appropriate complementary tool to focus pathological analysis on fluorescent LNs., (© 2018 Wiley Periodicals, Inc.)

Background: The size and focality of the primary tumor in breast cancer (BC) influence therapeutic decision making. The purpose of this study was to evaluate whether preoperative breast magnetic resonance imaging (MRI) is helpful for the assessment of tumor size and surgical planning in early BC., Methods: We performed a retrospective review of a prospectively collected database of 174 patients treated at a single institution for invasive BC who had complete documentation of the tumor size from mammography (MMG), ultrasonography (US), and MRI., Results: A total of 186 breast tumors were analyzed. Mean tumor size varied by imaging method: 14.7 mm by MMG, 13.8 mm by US, and 17.9 mm by MRI. The concordance between breast imaging techniques (BIT) and final pathology with a cutoff ≤ 2 mm was 34.8% for MRI, 32.1% for US, and 27.2% for MMG. US and MMG underestimated while MRI and MMG overestimated the real tumor size. Concordance was the same in premenopausal women for MRI and US at 35%, while concordance was higher in postmenopausal women for MRI. Correlations between size determined by BIT and histopathological size were best with MRI (0.59), compared to US (0.56) or MMG (0.42). Intrinsic subtypes of BC had different concordances according to imaging method, but no significant associations were found. MRI examination revealed additional lesions in 13.8% of patients, 69% of these lesions were malignant. MRI changed the surgical plan in 15 patients (8.6%), and the rate of mastectomy increased by 6.9%., Conclusions: MRI estimates BC tumor size more accurately than US or MMG, but a significant overestimation exists. Complementary MRI examination improved the concordance for tumor size between BIT and final pathology in 16.7%. MRI did not alter surgical planning for most patients and allowed more appropriate treatment for 8% of them., (© 2018 Wiley Periodicals, Inc.)

The aim of this study was to characterize the inflammatory infiltrate of the lymphoepithelioma-like carcinoma, a variant of squamous cell carcinoma clinically associated with a good prognosis. Immunohistochemistry was used to characterize 3 cases of lymphoepithelioma-like carcinoma in the uterine cervix, diagnosed over a period of 3 yr. The patients were between 30 and 50 yr old. Their cervical smears had shown atypical squamous cells of unknown significance or high-grade squamous intraepithelial lesions, and the initial cervical biopsy showed high-grade cervical intraepithelial neoplasia (CIN3) or squamous cell carcinoma. All patients underwent a Wertheim operation, 2 of which were preceded by a cervicectomy. Microscopically, all tumors were characterized by poorly defined sheets of undifferentiated squamous cells with a syncytial pattern and a dense background of infiltrating lymphocytes. Immunohistochemical analysis revealed that the lymphocytes were predominantly CD3 and CD8 T cells. The tumor lobules contained isolated CD8 T cells, whereas CD4 T cells and CD20 B cells surrounded the tumor lobules. CD56 NK cells and CD79 B cells were scattered in the tumor tissue. An in situ hybridization staining for Epstein-Barr encoding region was negative but all cases were immunohistochemically positive for P16. Follow-up varied between 2 mo and 2.7 yr. All 3 patients were disease free. Lymphoepithelioma-like carcinoma of the uterine cervix is a variant of squamous cell carcinoma, known for its better prognosis. The good prognosis of this tumor is potentially explained by the high levels of infiltrating CD8 T cells.

Background: Response to neoadjuvant chemotherapy (NACT), particularly pathologic complete response (pCR), is an independent predictor of favorable clinical outcome in breast cancer (BC). The accuracy of residual disease measurement and reporting is of critical importance in treatment planning and prognosis for these patients. Currently, gross pathological evaluation of the residual tumor bed is the greatest determinant for accurate reporting of NACT response. Fluorescence imaging (FI) is a new technology that is being evaluated for use in the detection of tumors in different oncological conditions., Objective: The aim of this study was to evaluate whether indocyanine green fluorescence imaging (ICG-FI) is able to detect residual breast tumor tissue after NACT in breast surgical operative specimens., Methods: Patients who underwent NACT for BC and were admitted for breast surgery were selected for participation in this study. Free ICG (0.25 mg/kg) was injected intraoperatively. Tumor-to-background fluorescence ratio (TBFR) was calculated on ex vivo samples from the surgical specimen., Results: One hundred and seventy-two samples from nine breast surgical specimens were evaluated for their fluorescence intensity. Among them, 52 were malignant (30.2%) and 120 were benign (69.8%). The mean TBFR was 3.3 (SD 1.68) in malignant samples and 1.9 (SD 0.97) in benign samples (p = 0.0002). With a TBFR cut-off value of 1.3, the sensitivity, specificity, negative predictive value, false negative rate, and false positive rate of ICG-FI to predict residual tumoral disease in breast surgical samples post-NACT were 94.2%, 31.7%, 92.7%, 5.8%, and 68.3%, respectively. If we restricted our analysis to only patients who achieved pCR, the negative predictive value for ICG-FI was 100%., Conclusions: These first observations indicate that ex vivo ICG-FI is sensitive but not sufficiently specific to discriminate between benign breast tissue and malignant residual tissue. Nevertheless, its negative predictive value seems sufficiently accurate to exclude the presence of residual breast tumor tissue on the operative specimen of patients treated by NACT, representing a potential tool to assist pathologists in the assessment of breast surgical specimens., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: No intraoperative imaging techniques exist for detecting tumor nodules or tumor scar tissues in patients treated with upfront or interval cytoreductive surgery (CS) after neoadjuvant chemotherapy (NAC). The aims of this study were to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of peritoneal metastases (PM) and evaluate whether it can be used to detect remnant tumor cells in scar tissue., Methods: Patients with PM from ovarian cancer admitted for CS were included. ICG, at 0.25 mg per kg of patient weight, was injected intraoperatively after explorative laparotomy before CS., Results: A total of 108 peritoneal lesions, including 25 scars, were imaged in 20 patients. Seventy-three were malignant (67.6%) and 35 benign (32.4%). The mean Tumor to Background Ratio (ex vivo) was 1.8 (SD 1.3) in malignant and 1.0 (SD 0.79) in benign nodules (P = 0.007). Of 25 post-NAC scars, the mean Tumor to Background Ratio (TBR) (in vivo) was 2.06 (SD 1.15) in malignant and 1.21 (SD 0.50) in benign nodules (P = 0.26). The positive predictive value of ICG-FI to detect tumor cells in scars was 57.1%., Conclusions: ICG-FI is accurate to demonstrate PM in ovarian cancer but unable to discriminate between benign and malignant post-NAC., (© 2017 Wiley Periodicals, Inc.)

In Belgium, breast cancer is the most frequent women's cancer accounting for to 35.3 % of the cases. In 2013, 10,778 newly diagnosed breast cancers have been reported in Belgium. Breast cancer has a relatively good prognosis with a 5 year overall survival of 88 %. Survival will be different regarding the subtype and stage at diagnosis. The review of the literature and the guidelines from ESMO and ASCO regarding the follow-up of patients with early breast cancer will be used as references. International guidelines recommend clinical visits (frequencies depending of the subtypes of breast cancer) with an annual mammography associated with an echography. MRI Imaging should be performed in " at risk " patients. A more extensive exploration should be proceede when a relapse is suspected during follow up. Indeed, studies have shown that intensive follow- up with several additional exams detect more recurrences without any impact on overall survival and lead to anxiety. The follow-up of patients treated for breast cancer has several objectives : - Detect a local recurrence or a second tumor ; - Diagnosis of a distant relapse ; - Detect side effects of treatment ; - Psycho-social impact of the disease and improve the quality of life.

There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes. Flow cytometric analysis of fresh tissue homogenates from untreated primary tumors show that PD-1 is principally expressed on CD4 + or CD8 + T cells and CTLA-4 is expressed on CD4 + T cells. The global proportion of PD-L1 + , PD-L2 + , LAG3 + , and TIM3 + tumor-infiltrating lymphocytes (TIL) was low and detectable in only a small number of tumors. Immunohistochemically staining fixed tissues from the same tumors was employed to score TIL and tertiary lymphoid structures (TLS). PD-L1 + , PD-L2 + , LAG3 + , and TIM3 + cells were detected in some TLS in a pattern that resembles secondary lymphoid organs. This observation suggests that TLS are important sites of immune activation and regulation, particularly in tumors with extensive baseline immune infiltration. Significantly improved overall survival was correlated with PD-1 expression in the HER2-enriched and PD-L1 or CTLA-4 expression in basal-like BC. PD-1 and CTLA-4 proteins were most frequently detected on TIL, which supports the correlations observed between their gene expression and improved long-term outcome in basal-like and HER2-enriched BC. PD-L1 expression by tumor or immune cells is uncommon in BC. Overall, the data presented here distinguish PD-1 as a marker of T cell activity in both the T and B cell areas of BC associated TLS. We found that immune checkpoint molecule expression parallels the extent of TIL and TLS, although there is a noteworthy amount of heterogeneity between tumors even within the same molecular subtype. These data indicate that assessing the levels of immune checkpoint molecule expression in an individual patient has important implications for the success of therapeutically targeting them in BC.

The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC. Tumor and normal breast tissues were analyzed using both flow cytometry and immunohistochemistry. TIL density distribution is a continuum with 25% of tumors identified as TIL-negative at a TIL density equivalent to normal breast tissues. TIL-positive tumors (75%) were equally divided into TIL-intermediate and TIL-high. Tumors had higher mean frequencies of CD4 + T cells and CD19 + B cells and a lower mean frequency of CD8 + T cells compare with normal tissues, increasing the CD4 + /CD8 + T-cell ratio. Tertiary lymphoid structures (TLS), principally located in the peri-tumoral stroma, were detected in 60% of tumors and correlated with higher TIL infiltration. PD-1 and PD-L1 expression were also associated with higher TIL densities and TLS. TIL density, TLS and PD-L1 expression were correlated with more aggressive tumor characteristics, including higher proliferation and hormone receptor negativity. Our findings reveal an important relationship between PD-1/PD-L1 expression, increased CD4 + T and B-cell infiltration, TIL density and TLS, suggesting that evaluating not only the extent but also the nature and location of the immune infiltrate should be considered when evaluating antitumor immunity and the potential for benefit from immunotherapies.

Purpose: Totally implantable vascular access devices (TIVADs) are widely used to administer chemotherapy to cancer patients. While great progress has been made with respect to breast surgical reconstruction to take into account both aesthetics and patients' perceptions of body integrity, these aspects have not been considered with regard to the impact of TIVAD. In order to address this practice gap, we have adapted our TIVAD implantation technique to improve cosmetic results. The aim of this study was to assess breast cancer patients' comfort level and aesthetic satisfaction with regard to TIVAD insertion., Methods: Patients with breast cancer admitted for chemotherapy at an outpatient clinic completed a previously validated survey evaluating three main domains: symptoms (pain, discomfort) related to the TIVAD itself in daily activity, information received before and during the surgical procedure, and cosmetic aspects regarding the port insertion site (scar, port, and catheter location)., Results: Between September 2010 and June 2011, 232 patients were evaluated. Cosmetic satisfaction with scar location was high (93.3 %). Information given to patients before and during the procedure had a major impact on both symptom perception in daily activity and on cosmetic satisfaction., Conclusions: Obtaining a more aesthetic scar by placing the TIVAD in the deltopectoral groove contributed to a high rate of cosmetic satisfaction. Furthermore, the relevance of information given to patients before and/or during surgery had a major impact on symptom perception. Therefore, we suggest including a pre-operative information session in the care pathway.

Background: EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel., Methods: HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks followed by surgery. Primary endpoint was percent (%) reduction in Magnetic Resonance Imaging (MRI) estimated Gadolinium (Gd) enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR) defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated., Results: Fifteen out of 20 scheduled patients were included: Six patients with estrogen receptor (ER)-negative/HER2-negative and 9 with ER-positive/HER2-negative BC. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to EndoTAG-1 were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively, and required permanent discontinuation of the EndoTAG-1. Moreover, two additional patients stopped EndoTAG-1 plus paclitaxel after 8 and 9 weeks due to clinical disease progression. Two patients had grade 3 increases in transaminases and 1 patient grade 4 neutropenia. pCR was achieved in 5 of the 6 ER-/HER2- and in none of the 9 ER+/HER2- BC patients. The mean % reduction in MRI estimated tumor volume at the end of EndoTAG-1 plus paclitaxel treatment was 81% (95% CI, 66% to 96%, p<0.001) for the 15 patients that underwent surgery; 96% for patients with pCR and 73% for patients with no pCR (p = 0.04)., Conclusions: The EndoTAG-1 and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2- patients. Further studies are warranted with need of premedication optimization., Trial Registration: ClinicalTrials.gov NCT01537536.