Oncologic safety of autologous fat grafting in primary breast reconstruction after mastectomy for cancer.

INTRODUCTION: Autologous fat transfer (AFT) is widely used to improve results of breast reconstructive surgery, but its safety is controversial. Our objective was to evaluate the oncologic safety of AFT in a homogeneous population of patients who underwent a total mastectomy with immediate reconstruction for breast cancer. METHODS: We performed a retrospective cohort study by identifying all patients who underwent immediate breast reconstruction after mastectomy for breast cancer from 2007 to 2015 in our center. A patient group with AFT performed in the 24 months after mastectomy was compared to a control group. RESULTS: Five hundred fifty cases were included, of whom 136 (24.7%) underwent at least one fat graft transfer. Median age was 51 years. Reconstruction was performed in 465 (84.5%) with an implant reconstruction. The median time from mastectomy to AFT was 13.8 months. The median follow up was 55.2 months. A total of 53 events were observed, including 10 (7.4%) in the AFT group and 43 (10.4%) in the control group. There was no difference in 5-year recurrence-free survival (RFS) between the groups. In the subgroup analysis, only lymph node involvement in patients who underwent AFT in the first 24 months after oncologic surgery appeared as a risk factor of recurrence. Among the 104 patients with lymph node involvement, 5-year RFS was 69.2% in patients with lipofilling vs 92.5% in patients without it (p = 0 0.0351). CONCLUSION: Performing early lipofilling in primary breast reconstruction after mastectomy for cancer seems to be oncologically safe. Lymph node involvement increases the risk of recurrence in this population.

French college of gynecologists and obstetricians (CNGOF) recommendations for clinical practice: Place of breast self-examination in screening strategies.

Breast cancer is the most common female cancer in the world. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of formal breast self-examination (BSE) as opposed to breast awareness has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: The Commission of Senology (CS) of the Collège National de Gynécologie et Obstétrique Français (CNGOF) respected and followed the Grading of Recommendations Assessment, Development and Evaluation method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE versus abstention from this examination led to detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from clinical breast examination by practitioners from the age of 25, and from organized screening from 50 to 74 (strong recommendation). In the absence of data on the benefits of BSE in patients aged over 75, for those at high risk and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these categories wish to undergo BSE, information on the benefits and risks observed in the general population must be given, notably that BSE is associated with a higher number of referrals, biopsies, and a reduced quality of life.

[Updated surgical indications and quality and safety indicators in the management of infiltrative breast carcinoma]. / Actualisation des indications chirurgicales et des indicateurs de qualité et sécurité des soins dans la prise en charge des carcinomes mammaires invasifs.

OBJECTIVES: Breast surgery is the cornerstone of breast cancer treatment. Its indications and procedures are constantly evolving. To update best practices, four questions were submitted to the Senology Commission (SC) of the Collège national des gynécologues et obstétriciens français (CNGOF), covering the indications and modalities of tumor surgery: (1) initially, (2) following neoadjuvant systemic treatment, (3) in case of local recurrence, and (4) the quality and safety of care indicators applicable to this surgery. METHODS: The CNGOF SC essentially based its responses on the clinical practice recommendations and guidelines of the French Cancer Institute concerning invasive carcinomas of the breast. Exclusion criteria were carcinoma in situ, sarcoma and axillary surgery. RESULTS: To define the type of breast surgery, knowledge of four parameters is essential: the patient's level of risk, the presence of metastases, the size of the breast tumor and its focality (assessed by the clinical/mammography/ultrasound tripod). (1) In the case of initial management, the 6 indications for mastectomy are patient choice (particularly in case of high risk), contraindication to radiotherapy, inflammatory cancer (T4d), surgery with positive margins (after several surgical intervention), surgery that cannot be performed as a monobloc in the case of tumors with multiple foci, and poor expected aesthetic results. All other situations should be treated conservatively. (2) The same criteria apply after neoadjuvant systemic treatment, with conservative treatment still possible whatever the size (excluding carcinomatous mastitis) and focality of the initial tumor. (3) In case of local recurrence, total mastectomy is the reference treatment, with a second conservative treatment reserved for patients with no risk factors for a second recurrence, and no poor prognostic factors, after validation in a multidisciplinary meeting. (4) Four quality and safety indicators apply to breast surgery: it must be performed after obtaining a histological diagnosis, within less than 6 weeks of mammography, in a single surgery in over 80% of cases, and followed by local radiotherapy in the case of conservative treatment. CONCLUSION: The indications and modalities of breast surgery are evolving rapidly. To improve aesthetic results, oncoplastic techniques, immediate breast reconstruction, and preservation of the skin or nipple-areolar complex need to be further developed and evaluated in the long-term. These developments must necessarily be accompanied in France by a training policy for breast surgeons.

[Place of breast self-examination in screening strategies. French College of Gynecologists and Obstetricians (CNGOF) recommendations for clinical practice]. / Recommandations pour la pratique clinique du CNGOF. Place de l'auto-examen des seins dans les stratégies de dépistage.

OBJECTIVES: Breast cancer is the most common female cancer in the world. In France, over 60,000 new cases are currently diagnosed, and 12,000 deaths are attributed to it annually. Numerous studies have shown that the risk of metastatic disease increases with tumor volume. In this context, it is useful to assess whether the regular practice of breast self-examination (BSE) has an impact on the number of cancers diagnosed, their stage, the treatments used and mortality. DESIGN: the CNGOF's Commission de Sénologie (CS), composed by 17 experts and 3 invited members, drew up these recommendations. No funding was provided for the development of these recommendations. The CS respected and followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method to assess the quality of the evidence on which the recommendations were based. METHODS: The CS studied 16 questions concerning BSE, individualizing four groups of women (general population, women aged over 75, high-risk women, and women previously treated for breast cancer). For each situation, it was determined whether the practice of BSE compared with abstention from this examination led to the detection of more breast cancers and/or recurrences and/or reduced treatment and/or increased survival. RESULTS: BSE should not be recommended for women in the general population, who otherwise benefit from a clinical breast examination (by the attending physician or gynecologist) from the age of 25, and from organized screening from 50 to 74 (strong recommendation). However, in the absence of data on the role of BSE in patients aged over 75, those at high risk of breast cancer and those previously treated for breast cancer, the CS was unable to issue recommendations. Thus, if women in these latter categories wish to undergo BSE, they must be given rigorous training in the technique, and information on the benefits and risks observed in the general population. Finally, the CS invites all women who detect a change or abnormality in their breasts to consult a healthcare professional without delay. CONCLUSION: BSE is not recommended for women in the general population. No recommendation can be established for women aged over 75, those at high risk of breast cancer and those previously treated for breast cancer.

The stake of informing patients of the risk of hypofertility after chemotherapy for breast cancer.

Introduction: Too few women with invasive breast cancer are informed of the risk of hypofertility after chemotherapy. However, this risk can be prevented by offering gamete preservation by a specialized team. We believe that if more women were informed about gamete preservation, more of them would accept it. Objectives: The primary objective is to describe each step of the oncofertility care pathway from provision of information to gamete preservation. The secondary objective is to estimate the impact of not receiving information by determining the proportion of women who would have undergone gamete preservation if they had been informed. Method: 575 women aged 18-40 years treated with chemotherapy for breast cancer between 2012 and 2017 in the Ouest-Occitanie region (~3 million inhabitants) were included. We first constructed a multivariate predictive model to determine the parameters influencing the uptake of the offer of gamete preservation among women who were informed and then applied it to the population of uninformed women. Results: Only 39% of women were informed of the risks of hypofertility related to chemotherapy and 11% ultimately received gamete preservation. If all had been informed of the risk, our model predicted an increase in gamete preservation of 15.35% in the youngest women (<30 years), 22.88% in women aged between 30 and 35 years and zero in those aged ≥36 years. We did not find any association with the European Deprivation Index (EDI). Conclusion: Oncologists should be aware of the need to inform patients aged ≤ 35 years about gamete preservation. If all received such information, the impact in terms of gamete preservation would likely be major.

A novel 3D culture model for human primary mammary adipocytes to study their metabolic crosstalk with breast cancer in lean and obese conditions.

Obesity is a negative prognosis factor for breast cancer. Yet, the biological mechanisms underlying this effect are still largely unknown. An emerging hypothesis is that the transfer of free fatty acids (FFA) between adipocytes and tumor cells might be altered under obese conditions, contributing to tumor progression. Currently there is a paucity of models to study human mammary adipocytes (M-Ads)-cancer crosstalk. As for other types of isolated white adipocytes, herein, we showed that human M-Ads die within 2-3 days by necrosis when grown in 2D. As an alternative, M-Ads were grown in a fibrin matrix, a 3D model that preserve their distribution, integrity and metabolic function for up to 5 days at physiological glucose concentrations (5 mM). Higher glucose concentrations frequently used in in vitro models promote lipogenesis during M-Ads culture, impairing their lipolytic function. Using transwell inserts, the matrix embedded adipocytes were cocultured with breast cancer cells. FFA transfer between M-Ads and cancer cells was observed, and this event was amplified by obesity. Together these data show that our 3D model is a new tool for studying the effect of M-Ads on tumor cells and beyond with all the components of the tumor microenvironment including the immune cells.

Access to information and oncofertility consultation for young women with breast cancer: a population-based study.

Non-menopausal women with breast cancer treated with chemotherapy are at intermediate risk of post-treatment amenorrhea and decreased fertility. Although they should receive appropriate information, studies until now show that this is inadequate. We investigated the proportion of women who received information about this risk during the pre-treatment consultation, and those who received an oncofertility consultation to preserve their gametes. We also analysed the medical and non-medical factors influencing the transmission of information to patients and their uptake of oncofertility consultations. We included women aged 18-40 years treated with chemotherapy for breast cancer between 2012 and 2017 in the Midi-Pyrénées region (ca. 3 million inhabitants), France. Studied variables were included in a multilevel model. Among the 575 women, 41% of the women received information and 28% received an oncofertility consultation. These two steps on the care pathway were significantly influenced by the type of care structure, the woman's age, her parity at the time of diagnosis, and the metastatic status of the cancer. Female oncologist gender was significantly associated with higher transmission rate. We found no association between neoadjuvant chemotherapy status, level of deprivation (EDI), triple-negative status, marital status, and first-degree family history of cancer and information transmission or uptake of oncofertility consultation. Our study shows that not enough women are informed and have recourse to an oncofertility consultation. Despite a legal obligation, the health care system does not offer the necessary conditions for access to oncofertility care.

Delayed Hypersensitivity Reaction to Titanium-coated Polypropylene Mesh in Breast Reconstruction.

Breast implant reconstructions increasingly incorporate meshes like the synthetic nonresorbable titanium-coated polypropylene mesh commercialized as Tiloop (Pfm medical). We report the case of a 48-year-old woman, with a medical history of nickel allergy, who presented with an extensive erythematous eruption, a periprosthetic reaction, and an axillary node reaction, 18 months after a unilateral prophylactic mastectomy. We excluded infectious, sarcoidosis and carcinomatosis. The patient's medical history, the clinical evolution, and the particularly fast and complete healing after removal of the mesh were suggestive of an unusual allergic reaction to the titanium in the titanium-coated polypropylene mesh. Titanium allergies are very rare events, predominantly described in the dental and orthopedic fields. We also discussed the hypothesis of a tardive red breast syndrome related to a synthetic mesh, also mediated by immunological response as described recently in another case report.

[Non-genetic indications for risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Indications des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: To determine the value of performing a risk-reducting mastectomy (RRM) in the absence of a deleterious variant of a breast cancer susceptibility gene, in 4 clinical situations at risk of breast cancer. DESIGN: The CNGOF Commission of Senology, composed of 26 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The Commission of Senology adhered to the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The Commission of Senology considered 8 questions on 4 topics, focusing on histological, familial (no identified genetic abnormality), radiological (of unrecognized cancer), and radiation (history of Hodgkin's disease) risk. For each situation, it was determined whether performing RRM compared with surveillance would decrease the risk of developing breast cancer and/or increase survival. RESULTS: The Commission of Senology synthesis and application of the GRADE method resulted in 11 recommendations, 6 with a high level of evidence (GRADE 1±) and 5 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the Commission of Senology members on recommendations to improve practice for performing or not performing RRM in the clinical setting.

Small Private Online Course in Teaching Oncology-Feedback After 1 Year: What Lessons?

In response to the complexity of medical care in oncology, 2 years ago, we designed a new teaching method (SPOC, Small Private Online Course) to improve cancer treatment and its management by emphasizing the community-hospital interface. The educational objective of this study was to evaluate after 1 year if the interest for this teaching remained constant over the long term to meet both educational and financial requirements. We designed a questionnaire including 18 questions grouped in 3 main parts describing the profile of the participants, his/her own experience, and the current utilization of the SPOC. Of 1574 participants of the 2 first sessions, 182 (11.5%) completed the questionnaire after 1 year. The majority of respondents were between the ages of 31 and 60 and belonged to a paramedical group (47.81%). After 1 year, 84.6% participants were satisfied or very satisfied with the content of the SPOC, 83.6% would recommended it, and 67% would be interested in using an updated SPOC again. Only 4.9% kept some contacts with other participants and 4.9% with teachers. 31.3% considered that the SPOC had a medium impact on their professional activity, 33.5% a lot, and 2.7% completely whereas 24.7% considered that it had little impact. The evaluation at 1 year showed that this digital learning method had a global positive impact on the professional practice of the participants. This study highlighted the empowerment of participants after this kind of teaching, but the network between participants was not enhanced.

Transvaginal minimally invasive approach: An update on safety from an anatomical, anatomopathological and clinical point of view.

INTRODUCTION: The aim of this work was to analyze the transvaginal approach in minimally invasive surgery in terms of anatomical, histopathological and functional characteristics, to show the safety of this surgical approach. METHODS: Anatomical study was first conducted by dissection on fresh cadavers of adult women in order to measure the distance between the vaginal incision and the ureters, rectum and hypogastric nerves. In parallel, an anatomopathological study detailed and compared the macroscopic and histological characteristics of the anterior and posterior surfaces of vaginal samples obtained from cadavers and patients in the context of a hysterectomy for benign pathology. Finally, patients who underwent a transvaginal approach nephrectomy or transplantation were retrospectively enrolled for a clinical examination and an evaluation of their sexuality. RESULTS: The anatomical study conducted on seventeen cadavers showed that the posterior vaginal fornix was remote from the major structures of the pelvis such as rectum, ureters, hypogastric plexus, which allowed a safe incision. Mechanical tests further demonstrated that the posterior vaginal fornix was more extensible than the anterior and histological features showed no major vascular or nervous structures. Ten patients were included in the retrospective clinical study. Long-term follow up showed no negative impact on the texture of the vagina or satisfaction from sexual intercourse. CONCLUSIONS: Anatomical, histological and functional data supported that transvaginal approach by posterior vagina fornix incision is a minimally invasive surgery that can be performed safely and effectively by a skilled surgeon in cases with a specific surgical indication for this approach.

Patients' satisfaction following laparoscopic cornuectomy for removal of hysteroscopic sterilization devices.

OBJECTIVES: To evaluate patients' satisfaction and evolution of pre-operative symptoms at 6 months following laparoscopic cornuectomy for hysteroscopic sterilization implants removal. MATERIAL AND METHODS: Retrospective study including all patients undergoing laparoscopic cornuectomy for implants removal in a tertiary care setting from January 2017 to October 2018. All women suffered from persistent and treatment-resistant gynecologic and non-gynecologic complaints since sterilization procedure. Patents' satisfaction was evaluated with the PGI-I questionnaire at 2 and 6 months following surgery. RESULTS: Overall, 104 patients were enrolled. Main symptoms comprised asthenia (n = 80), chronic pelvic pain (n = 80), arthralgia (n = 70), abnormal uterine bleeding (n = 42) and headache (n = 40). Cornuectomy was feasible in all cases and led to complete devices removal in 101 women. Mean length of stay was 1.8 days, while outpatient management was feasible in 45.2 % of cases. One grade 3 complication occurred along the study period (hemoperitoneum requiring reoperation). Surgery was associated with a significant decrease in symptom occurrence, except for alopecia and weight loss. Patients' satisfaction was high: 91 % at 2 months and 97.6 % at 6 months reported an improvement in their health status compared to baseline situation. Satisfaction regarding each symptom was consistent with overall assessment, with most patients reporting significant improvement at both 2 and 6 months. CONCLUSION: Laparoscopic cornuectomy is feasible and associated with high mid-term satisfaction in patients suffering from adverse effects attributed to hysteroscopic sterilization implants.

Prognostic value of lymphovascular space invasion in early-stage cervical cancer.

OBJECTIVE: Few prognostic factors likely to influence therapeutic management of early-stage cervical cancer are currently recognized. The objective of this study was to determine the prognostic value of lymphovascular space invasion (LVSI) in overall survival of patients with early-stage cervical cancer. METHODS: This is a retrospective study of patients treated for early-stage cervical cancer between January 1996 and December 2013 at Toulouse University Hospital and the Cancer Center Claudius Regaud Institute. Patients were included if they had FIGO 2018 stage IA1, IA2, IB1/2, or IIA1 cervical cancer. All patients had to have had surgery (conization, radical hysterectomy, or radical trachelectomy). The presence of LVSI was evaluated in the initial anatomic pathology reports of the excised tissue. The presence of LVSI was defined by the presence of epithelial tumor cells in the lumen of vessels, lined by endothelial cells. If the data were missing, the slides were reviewed by an expert pathologist. Comparative analyses of patient populations with and without LVSI invasion were performed, as well as analyses of overall and disease-free survival. RESULTS: A total of 158 patients were included in the analysis. Seventy-two (45.6%) patients had LVSI. More patients with LVSI received external radiotherapy in addition to standard treatment than patients without LVSI (53% vs 14%, p<0.0001). The overall survival of patients with LVSI (89.8%) was similar to that of patients without LVSI (91.5%) (p=0.39). For patients without lymph node involvement but with LVSI, disease-free survival at 5 years tended to be higher among those treated with external radiotherapy in addition to standard treatments (92.6% vs 79.8%, difference not tested due to the small number of events). CONCLUSION: Patients with early-stage cervical cancer with LVSI received external radiotherapy more often, and therefore had an overall survival at 5 years identical to patients without LVSI.

Estrogen Receptors and Endometriosis.

Endometriosis is a frequent and chronic inflammatory disease with impacts on reproduction, health and quality of life. This disorder is highly estrogen-dependent and the purpose of hormonal treatments is to decrease the endogenous ovarian production of estrogens. High estrogen production is a consistently observed endocrine feature of endometriosis. mRNA and protein levels of estrogen receptors (ER) are different between a normal healthy endometrium and ectopic/eutopic endometrial lesions: endometriotic stromal cells express extraordinarily higher ERß and significantly lower ERα levels compared with endometrial stromal cells. Aberrant epigenetic regulation such as DNA methylation in endometriotic cells is associated with the pathogenesis and development of endometriosis. Although there is a large body of data regarding ERs in endometriosis, our understanding of the roles of ERα and ERß in the pathogenesis of endometriosis remains incomplete. The goal of this review is to provide an overview of the links between endometriosis, ERs and the recent advances of treatment strategies based on ERs modulation. We will also attempt to summarize the current understanding of the molecular and cellular mechanisms of action of ERs and how this could pave the way to new therapeutic strategies.

Body Mass Index as a Major Risk Factor for Severe Breast Cancer-Related Lymphedema.

Background: A few studies have examined the characteristics of severe breast cancer-related lymphedema (BCRL). This study aims at analyzing the factors associated with severe lymphedema (LE) across a specific population of patients with BCRL. Methods and Results: Seventy-four patients with BCRL were included and cared for in the Lymphology Unit of Toulouse University Hospital between 2015 and 2016. Characteristics of patients and factors related to severe BCRL were retrospectively assessed. The median age at time of LE was 56 years (30-82). Thirty-five patients (47.3%) had a mastectomy and 72 (97.3%) an axillary lymphadenectomy. Among patients treated with radiation therapy (n = 72), 76.3% received lymphatic nodes irradiation. Fifty-five patients (74.3%) received chemotherapy and 52 (70.3%) a hormonal suppression therapy. A high proportion of patients had severe (>400 mL, 64.9%) and premature LE, with a median time of 13 months since onset of surgery (0.1-400.2). Weight gain between surgery and LE management was more prevalent in obese patients (p = 0.0164). Body mass index (BMI) at BCRL diagnosis was the only risk factor associated with severe LE (p = 0.0132). There was no significant association between LE severity and treatments received for breast cancer. Conclusions: Our study did not show any influence of tumor characteristics and cancer-related treatments on the severity of BCRL. Only BMI at BCRL diagnosis appears as a factor related to severe LE. These results highlight the importance of an education care unit promoting personalized nutritional lifestyle and encouraging physical activity early in the management of breast cancer.

Added-Value of Endometrial Biopsy in the Diagnostic and Therapeutic Strategy for Pelvic Actinomycosis.

The particularity of pelvic actinomycosis lies in the difficulty of establishing the diagnosis prior to treatment. The objective of this retrospective bicentric study was to evaluate the pertinence and efficacy of the different diagnostic tools used pre- and post-treatment in a cohort of patients with pelvic actinomycosis. The following data were collected: clinical, paraclinical, type of treatment, and the outcome and pertinence of the two diagnostic methods, bacteriological or histopathological, were evaluated. Twenty-seven women were included, with a pre-treatment diagnosis proposed for 66.7% (n = 18) of them. The diagnosis was established in 13.6% (n = 3) of cases through bacteriological samples, and in 93.8% (n = 15) of cases through histopathological samples, with endometrial biopsy positive in 100% of cases. The treatment was surgical with antibiotics for 55.6% (n = 15) of patients, medical with antibiotic therapy for 40.7% (n = 11) of patients, and surgical without antibiotics for one patient. All patients achieved recovery without recurrence, with a median follow-up of 96 days (4-4339 days). Our study suggested an excellent performance of histopathological analysis, and in particular endometrial biopsy, in the diagnosis of pelvic actinomycosis. This tool allowed early diagnosis and, in some cases, the use of antibiotic therapy alone, making it possible to avoid surgery.

18F-FDG PET/CT Identifies Predictors of Survival in Patients with Locally Advanced Cervical Carcinoma and Paraaortic Lymph Node Involvement to Allow Intensification of Treatment.

Our objective was to use 18F-FDG PET/CT to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and paraaortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynecologic oncology reviewed all 18F-FDG PET/CT scans. Metabolic parameters including SUVmax, metabolic tumor volume, and total lesion glycolysis (TLG) were determined for the primary tumor, pelvic lymph nodes, and PALNs. Associations between these parameters and overall survival (OS) were assessed with the Cox proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% confidence interval, 40.8-68.0). When adjusted for age, stage, and histology, pelvic lymph node TLG, PALN TLG, and PALN SUVmax were significantly associated with OS (P < 0.005). Conclusion:18F-FDG PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed.

Paclitaxel induces lymphatic endothelial cells autophagy to promote metastasis.

Cytotoxic therapy for breast cancer inhibits the growth of primary tumors, but promotes metastasis to the sentinel lymph nodes through the lymphatic system. However, the effect of first-line chemotherapy on the lymphatic endothelium has been poorly investigated. In this study, we determined that paclitaxel, the anti-cancer drug approved for the treatment of metastatic or locally advanced breast cancer, induces lymphatic endothelial cell (LEC) autophagy to increase metastases. While paclitaxel treatment was largely efficacious in inhibiting LEC adhesion, it had no effect on cell survival. Paclitaxel inhibited LEC migration and branch point formation by inducing an autophagy mechanism independent of Akt phosphorylation. In vivo, paclitaxel mediated a higher permeability of lymphatic endothelium to tumor cells and this effect was reversed by chloroquine, an autophagy-lysosome inhibitor. Despite a strong effect on reducing tumor size, paclitaxel significantly increased metastasis to the sentinel lymph nodes. This effect was restricted to a lymphatic dissemination, as chemotherapy did not affect the blood endothelium. Taken together, our findings suggest that the lymphatic system resists to chemotherapy through an autophagy mechanism to promote malignant progression and metastatic lesions. This study paves the way for new combinative therapies aimed at reducing the number of metastases.

Endermology treatment for breast cancer related lymphedema (ELOCS): Protocol for a phase II randomized controlled trial.

OBJECTIVES: Secondary lymphedema is a serious and debilitating condition, which may cause a range of cutaneous, infectious and joint complications with major psychological and social consequences. There is no curative treatment available. Initial symptomatic treatment includes Intensive Decongestive Treatment (IDT), which involves the use of multi-layered compression bandages, along with manual lymph drainage, physical exercise and skin care. IDT leads to an average decrease in limb volume of 20-40%, when compared to the contralateral limb. A better reduction may be obtained through the use of new adjuvant techniques, of which endermology is an example. The aim of this phase II study is to validate an IDT protocol combining endermology with standard of care in breast cancer related lymphedema. STUDY DESIGN: A standardised care protocol was proposed by the University Hospital of Toulouse's Lymphology team for the treatment of upper limb lymphedema after breast cancer surgery using Cellu M6 (LPG) Endermologie over 30 min. Every patient benefitted from IDT over 5 consecutive days, within the multidisciplinary Lymphology unit. Patients were randomised into three arms as follows: Arm 1: IDT for 5 days with bandages + manual lymphatic drainage. Arm 2: IDT with bandages + manual lymphatic drainage + Cellu M6 for 5 days. Arm 3: bandages + Cellu M6 for 5 days. During the study, patients will be followed-up for a period of 6 months. Use of LPG's Cellu M6 in combination with IDT may improve upper limb volume reduction compared with standard of care. By improving breast cancer related lymphedema, we expect to minimise further fluid build-up and to improve skin care, thus reducing the number of consultations and hospital admissions caused by this condition. The results of the present research protocol are expected to promote evidence supporting the use of endermology in the field of lymphology.