Background and Importance The compounding of injectable anticancer drugs in hospital pharmacies is in constant growth and requires innovation and development of flexible preparation methods while reducing the risk of exposure to hazardous drugs for healthcare workers. To this purpose, a robotic system implemented inside an isolator, Kiro Isolator® (Grifols, Spain), was designed. Aim and Objectives We report the qualification of the first Kiro Isolator® from a microbiological and preparation robustness point of view. Material and Methods Dose accuracy and precision were assessed for sampling volumes from 1 to 48 mL for three drugs used in our hospital: paclitaxel (viscous solution), vincristine (aqueous solution) and cyclophosphamide (aqueous solution with reconstitution). For each volume tested (1, 5, 10, 20 and 48 mL), five bags of paclitaxel and cyclophosphamide were produced. A volume of 2 mL was tested with vincristine only (n=10 bags). Tests were repeated over three days. All preparations were checked by gravimetric control using the scales of the robot with a weighing tolerance threshold set at 5%. For paclitaxel and cyclophosphamide preparations, an analytical control was performed to confirm the reliability of the robot's gravimetric control using an LC-MS. Deviation from the theoretical concentration was expected to be within +/-15%. Microbiological qualification was carried out by performing Media Fill tests (MFT) over three days. Results Overall, 75 bags of paclitaxel, 75 bags of cyclophosphamide and 30 bags of vincristine were produced. With the exception of the 1 mL volume, accuracy was validated with gravimetric control for all volumes tested. Analytical controls were compliant with the specifications except for three bags (two cyclophosphamide and one paclitaxel). We assume these results are false negatives due to an issue of homogenisation. Excepted the lowest volume of 1 mL, ANOVAs tests showed that for paclitaxel and cyclophosphamide the concentrations were not different from the theoretical concentrations. No growth was observed during a 15-day incubation of the MFT. Conclusion and Relevance Accuracy was validated for sampling volumes from 2 to 48 mL with a reliable gravimetric control. The robot's confinement ensures technician safety and environmental protection without affecting its performance. Since its qualification, nearly 20% of our total production is now carried out with this innovative robot. References and/or Acknowledgements Conflict of Interest No conflict of interest.

ContexteDans le cadre de l’expérimentation Onco’Link Thérapies orales (TO), nous avons mis en place dans notre établissement des consultations thérapeutiques (CT) binômées infirmiers diplômés d’État (IDE) et pharmaciens pour la primo-prescription de TO et le suivi des patients afin de garantir une prise en charge adaptée et suivie.ObjectifsL’objectif est d’évaluer la formation initiale et continue pour élaborer par la suite un support de formation (SF) pour les CT.MéthodeUn questionnaire de 12 questions a été distribué à 5 IDE, 4 pharmaciens et 1 interne réalisant les consultations TO et ayant été formés par leurs pairs, pour la majorité par compagnonnage, observation et en partie théorique. Une formation à la posture éducative est également réalisée. Les questions évaluaient le ressenti des professionnels de santé sur différents aspects de la CT avec des notions sur la maladie (physiopathologie, stratégies thérapeutiques), les traitements abordés en CT (galénique, posologie, effets indésirables [EI], suivi biologique, interactions médicamenteuses [IM], contre-indications [CI], médecines alternatives complémentaires [MAC]), sur les soins de supports (gestion des EI, capacité à adresser vers un autre professionnel de santé). Chaque professionnel pouvait avoir 3 réponses possibles : « très à l’aise », « moyennement à l’aise », « peu à l’aise ». Il renseignait sur le questionnaire sa profession et son ancienneté dans la pratique des CT. Une dernière question permettait de connaître les attentes de chacun sur la formation.RésultatsPour les IDE, la majorité se sentent « peu à l’aise » sur la galénique (3 IDE/5), les mécanismes d’actions (3/5), les CI (3/5), IM (4/5), et sur les MAC (4/5). À l’inverse, elles se sentent très à l’aise sur le suivi biologique (3/5), l’orientation vers d’autres professionnels (4/5), la gestion des EI (3/5). Les pharmaciens quant à eux étaient peu à l’aise sur l’orientation vers d’autres professionnels (3/5), sur les interactions TO et MAC (3/5). À l’inverse, ils se sentent très à l’aise sur les mécanismes d’action (3/5), les IM (3/5), la galénique (2/5). Les attentes pour un projet de formation initiale et continue seraient d’avoir un support théorique et pratique avec un approfondissement sur les MAC. De plus, les IDE souhaiteraient bénéficier d’une formation rapide sur des bases simples de pharmacologie sur les médicaments vus lors des CT.Discussion – conclusionCe questionnaire nous a permis de cibler les besoins des professionnels de santé interrogés. Ainsi, à terme l’objectif serait de mettre en place une formation théorique avec un quizz d’évaluation accompagnée d’une formation pratique et d’une habilitation. Ces formations seraient réalisées en multiprofessionnelles. Cet outil nous permettrait également d’actualiser les connaissances des professionnels de santé et par la suite de les réhabiliter. Avec l’arrivée de nouvelles IDE au sein de notre groupe de CT, nous pourrions également évaluer le SF mis en place.

ASCENT demonstrated the efficacy of Sacituzumab govitecan (SG) in patients (pts) with metastatic triple-negative breast cancer (mTNBC), and led to EMA approval in November 2021. We set up an ambispective bicentric cohort study to assess the real-world effectiveness and safety of SG in pts with mTNBC. This study included pts treated through the French Early Access Program from May 2021 to January 2023. Pts provided written consent for their clinical data to be reported. The cohort included 103 pts with a median age of 55 years [26-89]; 7/74 pts (9%) had BRCA1/BRCA2 germline mutation, 15 pts (15%) de novo metastatic disease and 32 pts (31%) brain metastases. Pts had previously received a median of 2 lines [1-10] of treatment in advanced setting, 29 pts (28%) and 6 pts (6%) had previously received anti-PD-1/PD-L1 and PARP inhibitors respectively. After a median follow-up of 9.6 months, median progression-free survival (PFS) and overall survival (OS) were 4.0 months (95%CI[3.4-5.3]) and 9.2 months (95%CI[7.2-NR]) respectively. The objective response rate (ORR) was 30% (2 pts achieved a complete response). Among pts with brain metastases, median PFS was 3.7 months (95%CI[2.6-6.2]) and OS 6.7 months (95%CI[6.3-NR]). Of 103 treated pts, 78 pts (76%) discontinued SG due to progressive disease (73 pts, 94%), toxicity (1 pt, 1%), physical deterioration (3 pts, 4%) or the patient's request (1 pt, 1%). Twenty-five pts (24%) were on treatment at data cut-off. The median duration of treatment was 3 months, corresponding to 6 cycles of SG. Dose reductions were required in 19 pts (18%) within a median of 2 cycles [2-11], due to gastrointestinal toxicity (6 pts), hematological toxicity (8 pts), liver enzyme elevation (1 pt), febrile neutropenia (3 pts), and physical deterioration (1 pt). There was no related death to SG. Our real-world data in mTNBC pts are consistent with results of the ASCENT trial in terms of ORR and safety, but observed PFS and OS are numerically shorter, including pts with brain metastases.

Background and Importance Excessive waiting time is one of the main causes of patient dissatisfaction in oncologic daily care unit (DCU). Lean management, dose banding, advanced prescription and automatisation are usually used in our hospital to improve patient care pathway. In our adult DCU (>26 000 patients/years), patients have to wait for their treatment less than an hour. Aim and Objectives The aim of this work is to reassess the time of availability in this DCU and to identify the factors influencing this time. Material and Methods It is an ambispective monocentric study in which human factors (n=2), equipment factors (n=7), organisational factors (n=4), productivity factors (n=16) and time-related factors (n=6) were recorded randomly between September 2021 and April 2022 (i.e. 15 days studied). Data were also extracted from CHIMIO® software and from our institutional 'LEAN tool' for real-time monitoring of patients in oncologic DCU, in order to calculate time between the prescription of the day and the dispensation of the treatment. Results The average number of patients and preparations manufactured per day were respectively 105 (+/-7) and 146 (+/-12); 52% of these preparations prepared the day before. The average number of preparations not prescribed in advance is 49 [18-62] (34%) for an average number of 31 patients [14-43] (30%). The average time to availability was 54 min (+/- 16) with a median of 60 min. On average, 12 [0-24] patients per day waited more than an hour after the prescription with a maximum waiting time of 360 min. Four days (27%) were identified with an average dispensing time greater than 60 min. During these critical days, a percentage of anticipated preparations less than 50%, with a high number of prescriptions (>30 patients) and particularly before 9:45 a.m. or between 12:00 and 14:00 p.m. were observed. We noticed also a higher productivity ([174-214] preparations), the lack of coordination (2 of 4 days), or additional productions (analgesic syringe preparations). Conclusion and Relevance Main impacting factors seem to be human factors and productivity. Time to availability became an essential quality indicator of our compounding anti-cancer unit. This study showed that our working procedures are efficient for a majority of patients, but not for all. References and/or Acknowledgements Conflict of Interest No conflict of interest

L’évolution des traitements anticancéreux s’est accélérée ces dernières années avec l’essor des thérapies orales. Les patients en bénéficiant doivent alors acquérir une certaine autonomie, particulièrement dans la gestion des effets indésirables (EI). En 2018, notre unité transversale d’éducation thérapeutique du patient (UTEP) a permis la mise à disposition d’un outil d’éducation thérapeutique du patient (ETP) sous la forme d’un jeu de société. Ce dernier permet d’accompagner les patients sous traitement anticancéreux oral, les aidants et les professionnels de santé. L’objectif de notre projet était de réunir et d’organiser les données nécessaires à l’élaboration d’un nouvel outil pédagogique sur les traitements oraux du cancer et leurs EI qui serait hébergé sur une plateforme virtuelle. Ce projet est coordonné par l’UTEP et le département de Pharmacie. Dans un premier temps, un référencement de toutes les thérapies orales anticancéreuses a été réalisé. Puis, nous avons répertorié les effets indésirables (très) fréquents pour chaque médicament, les grades de toxicité vulgarisés associés et les conduites à tenir en fonction de chaque EI. Toutes ces données, répertoriées sur un tableur Excel®, ont ensuite été validées par un oncologue. La virtualisation de l’outil pédagogique est réalisée directement via une application pré-existante et développée en interne au sein de l’établissement. Nous avons comptabilisé 91 thérapies orales et 175 EI classés eux-mêmes par systèmes. Pour chacun de ces EI, répertoriés via le site Observatoire du MEdicament, des Dispositifs médicaux et de l’Innovation Thérapeutique (OMéDIT) Haute Normandie, les grades de toxicité 1,2 et 3 vulgarisés ont été ajoutés, et les prises en charge répertoriées sous forme de questions « Vrai-Faux » multiples. L’outil pédagogique, sous forme de jeu en ligne, est disponible en version accès libre via Internet sur ordinateur et smartphone. L’outil sera directement alimenté à partir de la base de données préalablement construite. Cet outil permettra au patient utilisateur de mobiliser son savoir sur les EI des traitements puis de faire le lien entre sa thérapie et les EI associés. Le pharmacien clinicien, garant de la sécurité d’emploi des médicaments et de leurs effets indésirables associés, intervient habituellement à cette étape afin d’en vérifier la conformité. Le patient pourra ainsi acquérir les compétences nécessaires pour agir ou réagir en conséquence et devenir acteur de sa prise en charge. L’hébergement sur une plateforme virtuelle permet à la fois une diffusion facilitée, une mise à jour optimisée, et de répondre au contexte sanitaire de la COVID1-9. Néanmoins son utilisation est alors limitée aux patients disposant à minima d’un accès Internet et adeptes de ce type de format. L’outil pédagogique développé constitue ainsi un support supplémentaire pour les séances d’ETP, les consultations médicales, et les entretiens pharmaceutiques.

Purpose. - The tolerance of the concurrent use of radiotherapy, pertuzumab and trastuzumab is unknown. The purpose of this study was to evaluate the toxicity of this association in patients treated for HER2 positive metastatic and/or locally recurrent unrespectable breast cancer. Material and methods. - A retrospective study was performed in our institution for all consecutive patients treated with concurrent irradiation, pertuzumab and trastuzumab. The radiotherapy was performed while pertuzumab and trastuzumab were administrated as a maintenance treatment at the dose of 420 mg (total dose) and 6 mg/kg respectively every 3 weeks without chemotherapy. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Left ventricular ejection fraction (LVEF) was measured at baseline and then every 3-4 months. Results. - We studied 77 patients. treated in between 2013 and 2019 with median follow-up of 38 months (range 0-264 months). Median age was 53 years (33-86). There were 50 patients (64.9%) with metastatic and 27 patients (35.1%) with recurrent disease. All patients received docetaxel followed by P-T as first line treatment and they received 34 cycles (10-85) of pertuzumab and trastuzumab. All patients experienced partial or complete response according to RECIST criteria. Irradiation volumes were whole breast (41 patients, 53.2%) and chest wall (29 patients, 37.7%) at a dose of 50 Gy with a median duration of 39 days. Radiotherapy of lymph nodes was performed in 53 patients (68.8%) as following: supraclavicular-infraclavicular and axillary lymph nodes in 52 patients (67.5%), and internal mammary nodes in 31 patients (40.3%). For 20 patients. (26.0%) radiotherapy was palliative: bone irradiation (12 patients, 15.6%), whole-brain radiotherapy (2 patients, 2.6%), cerebral metastasis irradiation (6 patients). As early toxicity we observed: radio dermatitis as following: 36 patients (46.8%) presented grade I, 17 patients (22.1%) presented grade II, and 3 patients (3.9%) presented grade III. One patient (1.3%) presented grade II esophagitis. One patient (1.3%) presented asymptomatic decrease of LVEF during treatment and 6 patients (7.7%) presented a decrease of LVEF. There was no radiation-induced pneumonitis. As late toxicity, we observed 1 (1.3%) case of grade I and 1 (1.3%) with grade II telangiectasia. There was 1 case (1.3%) of grade III cardiac toxicity, 8 months after the concurrent treatment. Conclusion. - The concurrent use of radiotherapy, pertuzumab and trastuzumab is feasible with good tolerance. Larger prospective data with longer follow-up is needed to confirm these results. (C) 2021 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

La tolérance de l’association d’une radiothérapie concomitante à un traitement par pertuzumab et trastuzumab est encore inconnue. L’objectif était d’évaluer la tolérance de cette association chez des patientes prises en charge pour un cancer du sein localement évolué ou métastatique surexprimant le récepteur du facteur de croissance épidermique, HER2. Il s’agit d’un étude retrospective menée à l’institut Curie chez toutes les patientes recevant un traitement concomitant par pertuzumab, trastuzumab et irradiation. La radiothérapie a été délivré pendant un traitement par maintenance par pertuzumab et trastuzumab à respectivement 420 mg (dose totale) et 6 mg/kg toutes les trois semaines sans chimiothérapie. L’évaluation de la toxicité a été faite selon les Common Terminology Criteria for Adverse Events version 4.0 du National Cancer Institute. La fraction d’éjection ventriculaire gauche a été évaluée dans le bilan préthérapeutique et puis tous les 3 ou 4 mois. Nous avons étudié les dossiers de 77 patientes prises en charge entre octobre 2013 et décembre 2019 avec un suivi médian de 38 mois (extrêmes : 0-246 mois). L’âge médian était de 53 ans (extrêmes : 36-86 ans). Il y avait 50 cancers métastatiques au moment du diagnostic (soit 64,9 %) et 27 en récidive (soit 35,1 %). Toutes les patientes ont reçu comme première ligne thérapeutique une chimiothérapie à base de docétaxel suivie par pertuzumab et trastuzumab, avec un nombre de cycle médian de 34 (extrêmes : 10-85). Toutes les patientes avaient une réponse partielle ou complète selon les critères Response Evaluation Criteria In Solid Tumours (RECIST). Les volumes de radiothérapie étaient le sein (41 patientes, soit 53,2 %) et la paroi thoracique (29 patientes, soit 37,7 %) à la dose de 50 Gy, avec une durée médiane de traitement de 39 jours. Une irradiation des aires ganglionnaire régionales a été délivrée chez 53 patientes (soit 68,8 %) comme suit : irradiation sus/sous claviculaire axillaire chez 52 patientes (soit 67,5 %) et mammaire interne chez 31 patientes (soit 40,3 %). Pour 20 patientes, la radiothérapie était à visée palliative : osseuse (12 patientes, soit 15,6 %), de l’encéphale in toto (deux patientes, soit 2,6 %), de nodules métastatiques cérébraux (six patientes, soit 7,8 %). Comme toxicité aiguë nous avons observé : une radioépithéliite de grade 1 chez 36 patientes (soit 46,8 %), de grade 2 chez 17 (soit 22,1 %) et de grade 3 chez trois (soit 3,9 %). Une patiente a souffert d’ une œsophagite de grade 2 et une avait une baisse asymptomatique de la fraction d’éjection ventriculaire gauche en cours de chimiothérapie par pertuzumab, trastuzumab et radiothérapie. Comme toxicité tardive, nous avons observé des télangiectasies chez deux patientes, de grade 1 (soit 1,3 %) et de grade 2 (soit 1,3 %) ; un cas de cardiotoxicité de grade 3 est survenu 8 mois après la fin de la radiothérapie. Le traitement concomitant par pertuzumab, trastuzumab et irradiation semble avec un bon profil de tolérance, une étude prospective plus large avec un suivi plus longue reste cependant nécessaire pour confirmer ces résultats.

Abstract Background The NEOSPHERE trial suggested that pertuzumab (P) added to a combination of docetaxel and trastuzumab (T) as a neoadjuvant therapy in HER2 positive breast cancer (HER2+ BC) patients (pts) significantly enhances pathological complete response (pCR) rates. Here, we report our institution experience, focusing on stage III tumors. Methods We reviewed clinical and pathological response (residual cancer burden, RCB) in 355 HER2+ BC treated between 2010 and 2017 with neoadjuvant chemotherapy combined with T (n = 291) or TP (n = 64). Results were adjusted according to clinical stage, hormone receptors (HR) status, and chemotherapy regimen. In a subset of 157 pts matched on clinical TNM stage and HR expression (T, n = 98; TP, n = 59), a baseline pathological biomarker analysis was performed to assess TILs, PTEN, FOXP3 and PD-L1 expression. Results Among 355 patients, tumor clinical stages were T3 -T4 for 40% vs. 72% of T and TP pts (p  Conclusions This retrospective study did not suggest any benefit of neoadjuvant TP dual HER2 blockade regarding pathological response for stage III HER2+ BC. Baseline pathological expressions of PTEN, FOXP3, TILs, PD-L1 did not correlate with pathological response. Legal entity responsible for the study Institut Curie. Funding Institut Curie. Disclosure All authors have declared no conflicts of interest.

Abstract This abstract was withdrawn by the authors.

BackgroundHER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2.Patients and methodsWhole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation.ResultsHER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis.DiscussionThis is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.

Background Pomalidomide is a new oral antineoplastic that has a similar structure to thalidomide. It provides a last line in the treatment of multiple myeloma (MM), after thalidomide, bortezomib and lenalidomide. Purpose To estimate the tolerance and efficiency of pomalidomide after a period of one year of use under the status of Temporary Use Authorisation (TUA), and on a cohort of patients with MM who have relapsed. Materials and methods The analysis was conducted retrospectively from August 2012 to September 2013. The therapeutic use protocol provided by the manufacturer requires that the level of polymorphonuclear neutrophils (PMN) and platelets should be monitored. On one hand, biological tolerance was estimated from the patient’s complete blood count (CBC) (1/month), and on the other hand, clinical tolerance was estimated from the clinical and therapeutic data existing in the medical files. Efficiency was calculated from the rate of complete Ig on serum protein electrophoresis (SPE) or incomplete Ig i.e. free light chains (FLC) measured by immunofixation. Results Five patients, 2 men/3 women (P1, P2, P3, P4, P5) were treated with pomalidomide on 6th and even 8th line treatment. 3/5 patients presented MM with complete immunoglobulins (Ig) and 2/5 had MM with FLC. The initial dose of pomalidomide complied with the recommended regimen (4 mg/day for 21 days/28) associated with an antithrombotic. In terms of biological tolerance, 5/5 patients presented neutropenia (2 grade III/3 grade IV) and thrombocytopenia (3 grade 0/2 grade IV) during the first month. 4/5 patients again developed neutropenia (3 grade III/1 grade IV) and 3/5 patients thrombocytopenia (1 grade I/2 grade II) during the second month of treatment. In terms of clinical tolerance, adverse effects identified were: neuropathy of lower limbs grade III, paresthesias grade I, faintness, dizziness, episodes of daytime sweating, bronchospasm, coughs, intermittent diarrhoea, infections, peeling. In terms of efficiency, the SPE of 3/5 patients shows a decrease in the amount of complete Ig (P1: 49.2 to 4.7 g/l, P2: 16.4 to 4.8 g/l, P3: 42.4 to 35.7 g/l) within one year. The FLC rate decreased for P4 (1204 to 670 mg/l) and increased for P5 (850 to 1600 mg/l) within one year too. All in all, P1 and P4 have been able to continue treatment, P2 has benefited from an allograft of hematopoietic stem cells (HSCs), P3 has died and P5 is in remission. Conclusions 5/5 patients presented at least one serious adverse effect during the treatment. Adjusting the dose improves haematological tolerance but the Ig or FLC levels deteriorate, hence the need to increase the posology under cover of G-CSF. Pomalidomide demonstrated its efficiency and obtained its Marketing Authorisation (MA) in August, 2013 for use in 3rd-line treatment. No conflict of interest.

Background: The SHIVA trial is a multicentric randomised proof-of-concept phase II trial comparing molecularly targeted therapy based on tumour molecular profiling vs conventional therapy in patients with any type of refractory cancer. Results of the feasibility study on the first 100 enrolled patients are presented.Methods: Adult patients with any type of metastatic cancer who failed standard therapy were eligible for the study. The molecular profile was performed on a mandatory biopsy, and included mutations and gene copy number alteration analyses using high-throughput technologies, as well as the determination of oestrogen, progesterone, and androgen receptors by immunohistochemistry (IHC).Results: Biopsy was safely performed in 95 of the first 100 included patients. Median time between the biopsy and the therapeutic decision taken during a weekly molecular biology board was 26 days. Mutations, gene copy number alterations, and IHC analyses were successful in 63 (66%), 65 (68%), and 87 (92%) patients, respectively. A druggable molecular abnormality was present in 38 patients (40%).Conclusions: The establishment of a comprehensive tumour molecular profile was safe, feasible, and compatible with clinical practice in refractory cancer patients.

Using several complementary analytical methods, we demonstrated that the monoclonal antibody Trastuzumab (Tz), diluted in 0.9% sodium chloride can be stored in polyolefin infusion bags at 4°C or room temperature up to 6 months with no evidence of chemical or physical instability. No aggregation of Tz was observed and its three dimensional structure remains unaltered. Thus, the practical use of diluted Tz can be safely extended to optimize the workload of centralized preparation units and to minimize costs.

BACKGROUND:Although recent experimental data strongly suggest that platinum-based chemotherapy (PBCT) could improve the outcome of triple-negative breast cancer (TNBC), clinical data are lacking. Here, the authors reviewed clinical outcome in patients with metastatic TNBC treated with PBCT.PATIENTS AND METHODS:We conducted a retrospective analysis of all patients (N=143) treated for metastatic breast cancer with PBCT between 2000 and 2008, at Institut Curie, Paris, France. Ninety-three of them (63.7%) had TNBC. One-hundred twenty patients received cisplatin (CDDP). The main combination used was CDDP-ifosfamide, in 101 patients (70.2%).RESULTS:Median follow-up was 44 months. For the overall population (N=143), median overall survival (OS) and median progression-free survival (PFS) were 11 and 5 months, respectively. Objective response rate was 33.3% in the TNBC group versus 22% in non-TNBC, P=0.1. We observed no difference of OS, PFS and response duration. Other prognostic factors for poor OS were visceral metastasis sites (P<0.001). One patient died from sepsis during aplasia, 15 had to switch from CDDP to carboplatin because of CDDP-related toxicity.CONCLUSIONS:Metastatic TNBC patients treated with PBCT tended to have a higher response rate, without a significant improvement of PFS or OS, compared with other subtypes. Toxicity was acceptable. Longer observation and further analysis are warranted.

Several data support a central role for angiogenesis in breast cancer growth and metastasis. Observational studies have demonstrated that microvascular density (MVD) is a prognostic factor in invasive breast cancer, whereas others reached the opposite conclusion. Vascular endothelial growth factor is the most important angiogenic factor with proven significance in breast cancer, as it has been assessed in both experimental and clinical studies. Triple-negative breast cancer (TNBC) is a type of breast cancer which lacks estrogen, progesterone, and HER-2/neu receptors. MVD in both basal-like and TNBC is significantly higher than in non–basal-like and non-TNBC. In breast cancer and other malignancies, the development of agents that inhibit tumor angiogenesis has been an active area of investigation. In TNBC, clinical trials combining targeted agents and chemotherapy have failed to show substantial survival improvement. There is evidence that patients with TNBC may have a greater probability of obtaining some kind of clinical efficacy benefit from bevacizumab-based therapy.