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Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), after NAC, is aimed to select patient who should be safely spared of an axillary lymphadenectomy (ALND).GANEA 2 is a French prospective multi institutional trial, aimed to assess SLND after NAC. Objective To assess the risk of relapse for patients without previous axillary node involvement treated with NAC followed with a SLND without a systematic lymphadenectomy. Patients and Method Inclusion: FIGO stage T1-T3 infiltrating breast carcinoma, indication of NAC. Exclusion: inflammatory cancer, local relapse, contra-indication to NAC, NAC interrupted due to progressive disease. Design: indication to plan a NAC, axillary sonography with fine needle cytology before NAC to select patients without lymph node involvement, SLND after NAC. ALND was mandatory in case of SLN involvement (macro or micro-metastasis) or SLND failure. Follow-up was scheduled with a medical visit / 6 months with axillary assessment and a mammography each year. Follow-up results are updated every 6 months. Pathological analysis were carried out according to standard methods and classified according to the last American Joint Committee staging system. Studied parameters were SLND detection rate, pathological results on breast specimen and nodes, rate of relapse (axilla, breast, metastasis), and survival. Results From July 2010 to February 2014, 587 patients were enrolled, from 17 institutions, and experienced breast tumor surgery and a SLND after NAC. Each patient experienced breast surgery. A breast tumour pathological complete response was found in 21.3% (125/587). SLND rate was 97% (570/587), with a median number of 2 sentinel nodes (1-9). Patients with a sentinel detection failure (n=17) experienced a systematic lymphadenectomy, without any involvement (n=13), a micro-metastasis (n=2) and a macro-metastasis (n=2). A total of 140 patients had at least one sentinel node involved: macro-metastasis (n=86), micro-metastasis (n=54). A lymphadenectomy was performed in 128 cases: metastasis free (n=100), macro-metastasis (n=17), micro-metastasis (n=11). A total of 430 patients had a SLN metastasis free (75% ;430/570). A not mandatory lymphadenectomy was performed (n=14): metastasis free (n=11), macro-metastasis (n=2) and micro-metastasis (n=1). 17 patients were lost to follow-up. A total of 399 patients without sentinel node involvement were followed 2.3 years (from 0.5 to 5.6 yrs). At 3 years overall survival was 97.8% [94.9-99.1], disease free survival was 94.8% [91.0-97.1%]. Six patients died. Fifteen patients experienced a relapse: 8 metastasis, 4 homolateral breast, 2 controlateral breast, 1 homolateral axillary relapse. Conclusion This is the most important series of patients followed 2.3 years after SLND without axillary lymphadenectomy after NAC for an advanced breast cancer, showing acceptable results. The current series validate the safety of this conservative strategies avoiding systematic lymphadenectomy to patients without initially involved axillary node treated with NAC. Citation Format: Classe J-M, Loaec C, Alran S, Paillocher N, Tunon-Lara C, Gimbergues P, Faure-Virelizier C, Chauvet M-P, Lasry S, Dupre P-F, Verhaeghe J-L, De Blaye P, Gutowski M, Barranger E, Lecuru F, Lefevre Lacoeuille C, Loussert L, Lambaudie E, Ferron G, Campion L. Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): Follow-up of a prospective multi-institutional cohort [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S2-07.

Two thirds of node-positive breast cancer patients have limited pN1 disease and could benefit from a less extensive axillary lymph node dissection (ALND).172 breast cancers patients requiring an ALND were prospectively enrolled in the Sentibras Protocol of Axillary Reverse Mapping (ARM). Radioisotope was injected in the ipsilateral hand the day before surgery. ALND was standard. Removed lymph nodes were classified into non radioactive nodes and radioactive nodes (ARM nodes). Among ARM nodes, nodes located in the upper outer part of the axilla, above the second intercostal brachial nerve and lateral to the lateral thoracic vein were identified as "zone D ARM nodes". The main objective was: feasibility of identification of the zone D ARM nodes. Secondary objectives were: metastatic involvement and lymphedema rate.100% of patients had ARM nodes identified. The "zone D ARM nodes" were identified in 92% of cases. The rate of metastatic nodes was 60% in the all cohort, 31% in ARM nodes and 9% in zone D ARM nodes. Among those, metastatic rate was 6% in patients undergoing ALND for a positive sentinel node biopsy, 6% in case of primary ALND versus 14% after neo-adjuvant chemotherapy (p 0.05). After 34 months of median follow up, 27% of interviewed patients had a lymphedema.The ARM technique reliably identifies the "zone D ARM nodes". These nodes can also easily be identified using knowledge of axillary anatomy. In selected patients, a selective ALND sparing the zone D ARM nodes could be performed.

Background: The risk for developing breast cancer before the age of 40 is less than 1% and is similar worldwide. Breast cancer in young women is different from that of older women in terms of clinical and pathological characteristics and prognosis. We reviewed the evolution of breast cancer in young women aged < 40 years between 1980 and 2008 in the large database of the René Huguenin Hospital in France. Patients and Methods: Women diagnosed with a first breast cancer were prospectively included in the institution database. The analysis population included all women treated and followed between 1980 and 2008 for new breast cancer. The data were grouped into three periods: 1980-1990 (systematic pre-screening), 1991-2003 (first pilot screening experiences) and 2004-2008 (generalized systematic screening) and per age group comparing women Results: From 1980-2008, there were 20838 new breast cancers diagnosed, including 1431 (6.9%) in women Conclusion: Results of the retrospective analysis of a very large cohort of women less than 40 years diagnosed with breast cancer show that woman Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-19.

BACKGROUND: A prognostic index, the MD Anderson Prognostic Index (MDAPI), has been developed to help refine selection criteria for breast-conserving therapy after neoadjuvant chemotherapy. This score is based on initial nodal status N2/3, residual pathologic tumor size>2cm, a multifocal pattern of residual disease, and lymphovascular space invasion and ranged from 0 to 4. The objective of the current study was to validate the MDAPI for ipsilateral breast tumor recurrence. METHODS: Our study was a single-center retrospective analysis of a large prospectively collected breast cancer database. We identified data from 355 patients who received neoadjuvant chemotherapy and underwent breast-conserving therapy between 2002 and 2010. Predictive factors of ipsilateral breast tumor recurrence and the usefulness of the MDAPI were analyzed. Discrimitaion of models was also calculated. RESULTS: The median follow-up was 65 months, and the 5-year ipsilateral breast tumor recurrence-free survival rate was 90.7%. 5-year IBTR-free survival were 91.3% and 87.4% in MDAPI 0/1 and MDAPI 2+ categories (p = 0.07). (Multivariate analysis demonstrated that MDAPI (p = 0.01), Ki67 (p = 0.0004) and HER2 status (p = 0.0006) were associated significantly with ipsilateral breast tumor recurrence-free survival. Concordance index of the MDAPI was fair (0.6) but adding HER2 and ki67 status in the model improved concordance index : 0.75. CONCLUSIONS: The MDAPI was barely adaptable to the study patients in terms of predicting ipsilateral breast tumor recurrence. Biological factors such as ki67 and HER2 status should be included in the prognostic model. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-21.

Resume Introduction L’apnee du sommeil (SAS) est un syndrome frequent mais souvent ignore. Ce syndrome est de plus en plus decrit comme constituant un facteur de risque dans de nombreuses pathologies cardio-vasculaires, neurologiques et ophtalmologiques. Observation Les observations de trois patients ayant presente une occlusion veineuse retinienne (OVR) et chez qui un SAS a ete diagnostique dans le cadre du bilan etiologique sont rapportees. Un de ces patients ne presentait pas de facteur de risque vasculaire habituel. Discussion Les effets locaux et systemiques nocturnes induits par l’apnee du sommeil pourraient expliquer la survenue et/ou l’aggravation du tableau d’OVR. En effet, les OVR surviennent souvent la nuit a l’occasion de la diminution de la pression arterielle et du ralentissement circulatoire. L’OVR pourrait etre favorise par l’hypoxie induisant une vasodilatation et aggravant le ralentissement circulatoire, par l’augmentation de la pression intrathoracique et intracrânienne qui retentit mecaniquement sur le nerf optique. De plus, les reveils nocturnes repetes provoqueraient des poussees d’hypertension arterielle aggravant les conditions circulatoires. D’autres effets peuvent aussi jouer un role comme l’augmentation de la coagulation par action sur l’agregabilite des plaquettes et sur les facteurs de coagulation, l’hyperactivation du systeme sympathique, l’augmentation du stress oxydatif, de l’inflammation, et l’apparition de dysfonctions endotheliales. Conclusion Ce travail decrit pour la premiere fois l’association d’une OVR et d’un SAS dans une petite serie de patients. Le syndrome d’apnee du sommeil, en agissant sur la microcirculation oculaire, est peut-etre un facteur de risque supplementaire d’occlusion veineuse retinienne et/ou un facteur d’aggravation. Des etudes complementaires seraient utiles pour confirmer le lien entre ces deux affections.

Study objectives Flexible bronchoscopy (FB) is an invasive procedure associated with patient discomfort and frequent nose pain. A simple sedation procedure that does not require the intervention of an anesthetist is of interest. The aim of this prospective, randomized, double-blind study was to assess efficiency of nitrous oxide inhalation on the reduction of FB-induced discomfort in adult patients Design and settings Two hundred six patients were randomized to receive either a prefixed equimolar nitrous oxide/oxygen mixture (N 2 O) or a prefixed equimolar nitrogen and oxygen mixture (control). The primary outcome was stress as assessed by pulse rate and systemic BP during the procedure. Secondary outcomes were self-assessed pain using a visual analog scale (VAS) and patient satisfaction based on a questionnaire. Adverse events were recorded Results A significant increase in BP was observed only in the control group (p = 0.003), while pulse rate values did not differ between the two groups. As assessed by the VAS, pain was lower in the N 2 O group as compared to placebo (p = 0.02). Nose pain and cough were also significantly reduced by N 2 O. Adverse events, mostly anxiety, were reported in 10 patients Conclusion These results indicate that equimolar N 2 O inhalation is efficient in reducing patient discomfort and may be an alternative to general anesthesia

Resume Objectif. – La technique du capitonnage de l'aisselle sans drainage semble une alternative valable au drainage aspiratif. Ce capitonnage peut etre musculaire ou aponevrotique. Nous rapportons ici une evaluation du capitonnage musculaire, sans drainage. La presentation de nos resultats sur le capitonnage musculaire a ete egalement l’occasion de faire le point sur les autres alternatives visant a reduire la morbidite du drainage aspiratif. Patientes et methodes. – Un capitonnage musculaire a ete realise de maniere prospective au Centre Rene-Huguenin sur 152 patientes avec huit chirurgiens differents. Le recul est de 3,5 ans. La douleur a ete evaluee de maniere comparative avec 30 patientes operees avec un drainage aspiratif. Resultats. – Cette technique est d’un apprentissage simple. Elle est reproductible, elle simplifie les suites operatoires en permettant toujours une sortie au deuxieme ou troisieme jour postoperatoire sans soins a domicile. Il n’y a aucune augmentation des sequelles tardives. En revanche, les douleurs postoperatoires sont deux fois plus importantes dans les premieres semaines par rapport au drainage aspiratif et le taux de seromes est augmente. Discussion et conclusion. – Malgre la tres bonne efficacite, cette majoration des douleurs nous est apparue comme un obstacle majeur a la diffusion du capitonnage musculaire. Recemment, une modification technique importante realisant un capitonnage aponevrotique a ete publiee. Elle semble avoir une bonne efficacite, avec moins de douleurs que le capitonnage musculaire. Elle est en cours d’evaluation et pourrait devenir une alternative valable au drainage. Les alternatives techniques sont discutees. Les etudes publiees manquent, pour la plupart, de comparaison avec le drainage et ne prennent pas suffisamment en compte le retentissement sur la qualite de vie. Des travaux evaluant mieux cette qualite de vie sont actuellement en cours et devraient permettre, a l’avenir, de faire des choix prenant mieux en compte cette dimension.

The cost of mechanical ventilation (MV) is high. Efforts to reduce this cost, as long as they are not detrimental for the patients, are needed. MV with heat and moisture exchangers (HME) changed every 48 h is safe, efficient, and cost-effective. Preliminary reports suggest that the life span of these filters may be prolonged. We determined prospectively whether a hygroscopic and hydrophobic HME (Hygrobac-Dar; Mallinckrodt) provided safe and efficient heating and humidification of the inspired gases when changed only once a week. Patients who were considered to require mechanical ventilation for more than 48 h were included in the study. HMEs were initially set for 7 d. Efficient airway heating and humidification were assessed by clinical parameters (number of tracheal suctionings and instillations required, peak airway pressures) and hygrometric measurements performed by psychrometry. Resistance was measured from Day 0 to Day 7. Bacterial colonization of circuits and HMEs was studied. A total of 377 days of mechanical ventilation with 60 HMEs was studied. Clinical parameters and hygrometric measurements did not change between Day 0 and Day 7. Mean absolute humidity was 30.3 +/- 1.3 mg H(2)O/L on Day 0 and 30.8 +/- 1.5 mg H(2)O/L on Day 7 (p = 0.7). Endotracheal tube occlusion never occurred. Three HMEs were replaced prematurely because of insufficient absolute humidity. This rare event occurred only in patients with COPD and after the third day of use. In addition, the absolute humidity delivered by the HMEs was significantly lower in patients with COPD than in the rest of the population. Resistance did not change from Day 0 to Day 7 (2.4 +/- 0.3 versus 2.7 +/- 0.3 cm H(2)O/L/s; p = 0.4). Bacterial samples of both circuits and ventilator sides of HMEs were sterile in most cases. We conclude that mechanical ventilation can be safely conducted in non-COPD patients using an HME changed only once a week, leading to substantial cost savings (about $110,000 per year if these findings were applied to the university-affiliated hospitals in Paris).

L’omalizumab (OMZ) a une AMM depuis 2005 dans l’asthme severe allergique avec un allergene perannuel retrouve. Ce travail a pour objectif d’evaluer l’adequation de la prescription de l’OMZ et son efficacite en utilisation courante dans un centre de pneumologie. Patient et methodes Etude retrospective monocentrique. Tous les pts (n = 55) ayant recu de l’OMZ entre 2003 et 2014 ont ete inclus. Les criteres de severite, l’adequation de la prescription par rapport aux recommandations de l’AMM et l’efficacite du traitement ont ete analyses. Resultats Tous les pts avaient un asthme severe (VEMS moyen 61 %, ACT moyen 11,6, Nombre moyen d’EA : 5,44/an). Cinquante-quatre pour cent des patients recevaient une corticotherapie orale, tous avaient des doses elevees de CSI (> 1000 mcg/j). Quatre-vingt-cinq pour cent avaient un allergene perannuel. 10 pts avaient des taux d’IgE ou un poids hors des tables d’AMM : IgE 1500 : n = 3, IgE > 30 et Conclusion La prescription d’OMZ n’etait pas conforme aux recommandations dans 15 % des cas du fait de l’absence d’allergene perannuel identifie et dans 18 % des cas car ils etaient hors des tables de dosage recommande. L’efficacite de 66 % est proche de la litterature, mais 18 % ont presente un EI imposant l’arret du traitement.

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk-benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted.

Background: The major factor influencing the prognosis of cutaneous malignant melanoma (MMs) is the maximum thickness of the tumor as measured by Breslow's method. However, it has been reported that thin melanomas, which should have an excellent prognosis, may have the potential to metastasize, some with an unusually rapid course. Objective: Our purpose was to examine prognostic indicators in relation to unusually rapid aggressive behavior in patients with thin MMs ( Methods: We describe nine cases of thin MM ( Results: The particular aggressiveness of these thin melanomas was reflected by the short disease-free interval (3 years or less) in all nine patients. The recurring thin MM more frequently involved head and neck sites, occurred in male patients, and showed Clark's level III and IV. Conclusion: Our review suggests that the head and neck area is particularly involved by unusually rapidly recurring thin MM. Possible explanations are the specific problems of surgical management and the greater sun exposure of this location.

Background To evaluate whether predictive factors of axillary lymph node metastasis in female breast cancer (BC) are similar in male BC. Patients and methods From January 1994 to May 2011, we recorded 80 non-metastatic male BC treated at Institut Curie (IC). We analysed the calibration and discrimination performance of two nomograms [IC, Memorian Sloan-Kettering Cancer Center (MSKCC)] originally designed to predict axillary lymph node metastases in female BC. Results About 55% and 24% of the tumours were pT1 and pT4, respectively. Nearly 46% demonstrated axillary lymph node metastasis. About 99% were oestrogen receptor positive and 94% HER2 negative. Lymph node status was the only significant prognostic factor of overall survival (P = 0.012). The area under curve (AUC) of IC and MSKCC nomograms were 0.66 (95% CI 0.54–0.79) and 0.64 (95% CI 0.52–0.76), respectively. The calibration of these two models was inadequate. Conclusions Multi-variate models designed to predict axillary lymph node metastases for female BC were not effective in our male BC series. Our results may be explained by (i) small sample size (ii) different biological determinants influencing axillary metastasis in male BC compared with female BC.

Our objective was to assess the global cost of the sentinel lymph node detection [axillary sentinel lymph node detection (ASLND)] compared with standard axillary lymphadenectomy [axillary lymph node dissection (ALND)] for early breast cancer patients.We conducted a prospective, multi-institutional, observational, cost comparative analysis. Cost calculations were realized with the micro-costing method from the diagnosis until 1 month after the last surgery.Eight hundred and thirty nine patients were included in the ASLND group and 146 in the ALND group. The cost generated for a patient with an ASLND, with one preoperative scintigraphy, a combined method for sentinel node detection, an intraoperative pathological analysis without lymphadenectomy, was lower than the cost generated for a patient with lymphadenectomy [€ 2947 (σ = 580) versus € 3331 (σ = 902); P = 0.0001].ASLND, involving expensive techniques, was finally less expensive than ALND. The length of hospital stay was the cost driver of these procedures. The current observational study points the heterogeneous practices for this validated and largely diffused technique. Several technical choices have an impact on the cost of ASLND, as intraoperative analysis allowing to reduce rehospitalization rate for secondary lymphadenectomy or preoperative scintigraphy, suggesting possible savings on hospital resources.

Obstructive sleep apnea syndrome (OSAS) is a very common disease and has recently been increasingly incriminated in the initiation and progression of numerous cardiovascular, neurologic, and ophthalmologic diseases. In ophthalmologic practice, it may be related to glaucoma, nonarteritic anterior ischemic optic neuropathy, visual field defects, papilledema, central serous chorioretinopathy, and floppy eyelid syndrome. Because of personal observations, we investigated its link with retinal vein occlusion (RVO).We report the observations on three patients who presented with retinal vein occlusion and who were investigated positively for OSAS, including patients with no conventional vascular risk factors.The local and systemic effects of OSAS could explain, in some patients, the occurrence and/or the aggravation of RVO. The first-stage effects of OSAS are nocturnal hypoxemia, hypercapnia, intrathoracic pressure changes, arousals, and sleep fragmentation. RVO could be a consequence of a slow-down of blood flow circulation secondary to hypoxemia and elevated nocturnal intracranial pressure. The arousals cause an additional acute increase in arterial blood pressure. Ancillary effects include increased platelet aggregability, increased sympathic activation, oxidative stress, vascular endothelial dysfunction, inflammation, and metabolic dysregulation.This short series for the first time reports RVO patients presenting with OSAS. This suggests that OSAS, by acting on retinal microcirculation, could be an additional risk factor for the occurrence or the aggravation of RVO. Further studies are needed to confirm this possible relationship.

Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), performed after NAC, must select patient who should be spared of an axillary lymph node dissection (ALND). The application of SLND for staging the axilla after NAC for patient who initially had a proven axillary lymph node involvement remains controversial because of a low detection rate (DR) and a high false negative rate (FNR). Objective The aim of GANEA 2 trial was to assess the DR and the FNR of SLND after NAC in the particular case of patients with a proven axillary lymph node involvement. Patients and Method GANEA 2 was validated by scientific and ethical national boards. Inclusion criteria: FIGO stage T2-T3 infiltrating breast carcinoma, indication of NAC, surgery (radical or conservative) after NAC and signed consent form, Exclusion criteria: inflammatory cancer, local relapse, previous surgical removal of the tumour, mental disorder, pregnancy or no contraceptive method, contra-indication to NAC, NAC interrupted due to progressive disease. Design: Diagnosis and indication to plan a NAC, control of inclusion and exclusion criteria, consent form signature, axillary sonography with fine needle cytology before NAC to select patients with a proven lymph node involvement. After NAC patients underwent both SLND, with the combined technique Blue dye and radiolabeled colloid, and complementary ALND. Pathological procedure: Pathological analysis, of sentinel and non sentinel nodes, carried out according to standard methods and classified according the last American Joint Committee staging system and Sataloff classification. Studied parameters were detection rate, false negative rate and Sataloff grading on tumor and lymph nodes. We evaluated particularly the likelihood that the FNR in patients with one or more SLN examined was greater than 10%. Patients with no lymph node involvement before NAC underwent only a SLND with an ALND only in the case of SLN macro-metastasis with a rigorous follow up. They are not part of this abstract. Results From July 2010, to February 2014, 242 patients from 19 institutions were enrolled, with a proven axillary lymph node involvement before NAC. After NAC, 1/3 had metastasis free axillary lymph node (80/142). Detection rate was 83.1% (201/242). Half of the patients with a detection failure had an involved ALND. The false negative rate was 14.2% in the whole series but 24.5% in the case of only 1 SLN resected, and 8% in case of more than 1 SLN resected. In case of involved SLN, half of the patients had involved ALND. Considering the node Sataloff scoring, 18 of the 20 false negative cases were grade C or D (n=15 grade C, metastatic disease and therapeutic effect; n = 3 grade D, metastasis and no therapeutic effect). Conclusion Among patients treated by NAC for a large operable breast cancer with proven involved lymph node before NAC, who had only 1 SLN examined, the false negative rate was 24.5%. SLND with the combined technique, provides a FNR of less than 10% only in the case of 2 or more SLN resected. Citation Format: Jean-Marc Classe, Loic Campion, Severine Alran, Christine Tunon de Lara, Pierre Francois Dupre, Christelle Faure, Nicolas Paillocher, Serge Lasry, Marie Pierre Chauvet, Gilles Houvenaeghel, Marian Gutowski, Pascaline De Blaye, Charlotte Ngo, Emmanuel Barranger, Jean Luc Veraeghe, Celine Lefebvre, Jean Francois Rodier, Virginie Bordes, Helene Charitansky, Gwenael Ferron, Pierre Gimbergues. Sentinel node surgery after neoadjuvant chemotherapy in patient with axillary node involvement: The French GANEA 2 prospective multi-institutional trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-01.

We compared the impact of neoadjuvant chemotherapy on pathologic response and outcome in operable invasive lobular breast carcinoma (ILC) and invasive ductal breast carcinoma (IDC).We extracted from our database all patients with pure invasive lobular (n=118, 14%) or pure invasive ductal carcinomas (n=742, 86%). Their treatment included neoadjuvant chemotherapy, adapted surgery, radiotherapy and adjuvant hormonal treatment.Compared with IDC, ILC presented with larger tumors (T3: 38.1% versus 21.4%, P=0.0007), more N0 nodes status (55.9% versus 43.3%, P=0.01), less inflammatory tumors (5.9% versus 11.8%, P=0.01), more hormone receptor positivity (65.5% versus 38.8%), lower histological grade (P0.0001). Final surgery was a mastectomy in 70% of patients with ILC (34% were reoperated after initial partial mastectomy) and in 52% of IDC after 8% of reoperation (P=0.006). A pathological complete response (pCR) was achieved in 1% of ILC and 9% of IDC (P=0.002). The outcome at 60 months was significantly better for ILC, but histologic type was not an independent factor for survival in multivariate analysis.ILC appeared less responsive to chemotherapy but presented a better outcome than IDC. While new information on biological features of ILC is needed, we consider that neoadjuvant endocrine therapy in hormone receptor-positive ILC may be a more adapted approach than neoadjuvant chemotherapy.

Axillary padding without drainage appeared to be a valuable alternative technique to vacuum drainage. The technique employs local muscles or the axillary aponeurosis for padding. We report here the clinical evaluation of muscular padding without drainage. The analysis of these results prompted us to also do a literature search for other alternatives aimed at reducing morbidity due to vacuum drainage.Muscular padding was prospectively performed by 8 different surgeons on a total of 152 patients at the Centre Rene-Huguenin (Saint-Cloud, France). Follow-up has attained 3.5 years. A comparative assessment of pain was conducted in 30 patients operated on with vacuum drainage.This technique is easy to learn and reproducible. It facilitates post-operative follow-up, always allowing discharge at the 2nd or 3rd post-operative day without any home nursing. The late sequels are not increased. In contrast, pain was twice more intense during the first post-operative weeks compared with vacuum drainage, and the seroma rate was also increased.Despite good efficacy, this worsening of pain is a major obstacle to the routine use of muscular padding. A technical improvement has been published very recently where the axillary aponeurosis was used to pad the axilla. It seems to be equally efficient but less painful than muscular padding. This technique is under clinical evaluation and could appear as a valuable option to vacuum drainage. Other alternatives are discussed. Most studies lack a direct comparison with vacuum drainage and a satisfactory evaluation of quality of life is also omitted. New studies with quality of life scales are ongoing. They should allow us to choose options that take this aspect into account in the future.

Tamoxifen has been used for two decades as adjuvant therapy for breast cancer. It is also now being used to try and prevent this disease in women at high risk. A series of 89 patients who developed endometrial cancer on adjuvant has been identified from nine French cancer institutes. Although there was a high frequency of superficial, generally well-differentiated forms, some patients did have aggressive disease with a relatively poor outcome and there were 10 deaths from endometrial carcinoma. These data support gynaecological surveillance of women receiving tamoxifen therapy.

Among the proteases involved in the tumor invasion process, components of the plasminogen activator system (plasminogen activator type-urokinase uPA, its membrane receptor uPAR and its two inhibitors PAI-1 and PAI-2) appear to define high risk patients in primary breast cancer. As individual analysis of each component of the plasminogen activator system does not reflect the complex interactions between the different components, we studied the prognostic impact of a dissemination risk index combining the four variables. We found that this index was the most powerful prognostic factor, particularly in node-negative patients.

Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk-benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted.

The major factor influencing the prognosis of cutaneous malignant melanoma (MMs) is the maximum thickness of the tumor as measured by Breslow's method. However, it has been reported that thin melanomas, which should have an excellent prognosis, may have the potential to metastasize, some with an unusually rapid course.Our purpose was to examine prognostic indicators in relation to unusually rapid aggressive behavior in patients with thin MMs (0.76mm).We describe nine cases of thin MM (.76mm) that exhibited a recurrence or metastasis during a follow-up period ranging from 3 to 10 years, among computerized records of 1118 MMs treated in a multicenter epidemiologic study. The data obtained from these nine cases were compared with nonrecurring thin MM (149 cases) of the same cohort.The particular aggressiveness of these thin melanomas was reflected by the short disease-free interval (3 years or less) in all ine patients. The recurring thin MM more frequently involved head and neck sites, occurred in male patients, and showed Clark's level III and IV.Our review suggests that the head and neck area is particularly involved by unusually rapidly recurring thin MM. Possible explanations are the specific problems of surgical management and the greater sun exposure of this location.

Background: To evaluate whether predictive factors of axillary lymph node metastasis in female breast cancer (BC) are similar in male BC. Patients and methods: From January 1994 to May 2011, we recorded 80 non-metastatic male BC treated at Institut Curie. We analysed the calibration and discrimination performance of two nomograms (Institut Curie (IC), Memorian Sloan-Kettering Cancer Center (MSKCC)) originally designed to predict axillary lymph node metastases in female BC. Results: 55% and 24% of the tumours were pT1 and pT4 respectively. 46% demonstrated axillary lymph node metastasis. 99% were estrogen receptor positive and 94% HER2 negative. Lymph node status was the only significant prognostic factor of overall survival (p = 0.012). The area under curve (AUC) of IC and MSKCC nomograms were 0.66 (95%CI, 0.54–0.79) and 0.64 (95% CI, 0.52–0.76) respectively. The calibration of these two models was inadequate (Table 1). Conclusion: Multivariate models designed to predict axillary lymph node metastases for female BC weren't effective in our male BC series. Our results may be explained by a) small sample size b) different biological determinants influencing axillary metastasis in male BC compared to female BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-19.

The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk [RR]: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.

There has been growing interest in intraductal carcinomas of the breast (DCIS) over the last ten years mainly because of their increasing frequency and their difficult diagnosis. Their natural history is often surprising. For the time being, it is impossible to establish which proportion of DCIS might turn into an infiltrating carcinoma, and which factors are predictive for such a risk. These uncertainties are responsible for many controversies about their treatment. Based on a critical review of the latest publications, this paper deals with the possibilities of conservative treatment, challenging the remarkable results of total mastectomy (nearly 100% survival at 10 years). The risk of conservative treatment depends on the frequency of local recurrence, and on the potential vital risk of such recurrences, knowing that half of these recurrences will develop in an invasive, and no longer in situ, pattern. Randomized trials are being conducted on this question; they will not give an answer before the year 2000. In the mean time, conservative treatment seems to be reasonable for small low grade histologic lesions widely excised by surgery, and with rigorous possibilities of follow-up. The operation is followed by external irradiation. In case of recurrence, mastectomy has to be. It is not impossible that, performed under these conditions, a slight increase in mortality might follow such a strategy, thus heavily balancing the benefits of conserving the breast. Besides, surgical excision alone should only be performed as part of randomized trials, or for infra-centimetric lesions discovered by histology after resection of supposed benign lesions.

To evaluate the possible involvement of obstructive sleep apnea (OSA) in retinal vein occlusion (RVO).From the medical records of 63 consecutive patients with RVO, 30 patients with 2 of the 3 following risk factors for OSA were selected for further screening from February 1, 2008, through March 31, 2009: associated cardiovascular disease, snoring, or daytime sleepiness.Of the 30 selected patients, 23 (77%) had OSA. If all 33 of the unscreened patients did not have OSA, the OSA prevalence would have been 37%. Among the patients with OSA, the mean apnea-hypopnea index (AHI) was 21; OSA was mild (AHI15) in 13 patients, moderate in 5 patients (AHI 15-30), and severe (AHI30) in 5 patients. The AHI was correlated with body mass index (P = .02).We found a higher than expected prevalence of OSA in a series of patients with RVO. Our findings suggest that OSA could be an additional risk factor that plays an important role in the pathogenesis of RVO or at least that it is a frequently associated condition that could be a triggering factor. This association may explain why most patients discover visual loss on awakening. It is too early to assess whether OSA treatment could improve visual outcome of RVO, but it seems vital to recognize OSA in RVO for the general health of the patient.

e11539 Background: The increased use of neoadjuvant chemotherapy (CT) in breast cancer (BC) management has raised new questions regarding the optimal locoregional treatment. The aim of this retrospective study was to compare the outcomes of BC patients (pts) with pathological N0 status (pN0) following primary CT and conservative surgery who received breast radiotherapy with or without lymph node irradiation. Methods: Between 1990 and 2004, 1054 patients received preoperative CT for locally advanced BC. Data from 248 pts (23.5%) with clinical N0 (164 pts) or N1-N2 (84 pts) lymph node status at diagnosis and pN0 status after primary CT were studied. Among them, 93 pts (37.5%) received breast irradiation alone and 155 pts (62.5%) underwent locoregional irradiation. Outcome was assessed in relation to lymph node recurrence, disease-free survival (DFS) and overall survival (OS). Results: Both groups were comparable in terms of baseline characteristics. With a median follow-up of 88 months, 3 pts experienced nodal recurrence in the breast irradiation alone group compared with 2 pts in the locoregional irradiation group (p>.05). Among the 164 N0 pN0 pts, the 5-year DFS and OS rates were respectively 84% and 89% vs 84% and 95%, according to whether they received (n=87) or not (n=77) lymph node irradiation(p>.05). Among the 84 N1-N2 pN0 pts, same outcome values did not show any significant difference according to group of treatment: 72% and 88% in 68 pts treated with locoregional irradiation vs 81% and 81% in 16 pts treated with breast irradiation alone (p>.05). Conclusions: Our results suggest that breast irradiation alone is not associated with a higher risk of regional recurrence in locally advanced BC pts with pN0 status after neoadjuvant chemotherapy. Whether this allows the omission of lymph node irradiation for such strategy should be addressed prospectively. No significant financial relationships to disclose.

Introduction L’apnee du sommeil (SAS) est un syndrome frequent mais souvent ignore alors qu’il est lie a une morbidite et une mortalite accrue. Ce syndrome est de plus en plus decrit comme constituant un facteur de risque dans de nombreuses pathologies cardio-vasculaires, neurologiques et ophtalmologiques. Materiels et Methodes Etude prospective de 30 patients presentant une occlusion veineuse retinienne chez qui a ete recherche un syndrome d’apnee du sommeil par polygraphie ventilatoire nocturne. Resultats L’âge moyen etait de 56 ans. 76 % (23 sur 30) presentaient un syndrome d’apnee du sommeil defini par un index apnee-hypopnee superieur a 5 par heure. Chez les patients positifs, cet index etait en moyenne de 21,95 par heure (min 7/h ; max 74/heure), le nombre moyen d’hypopnees etait de 12/heure, la moyenne de la SpO2 minimale etait de 77,3 %. Discussion Dans cette serie, la prevalence du SAS est tres superieure a celle de la population generale (proche de 5 %), laissant supposer un lien entre les effets locaux et systemiques nocturnes induits par l’apnee du sommeil et la survenue du tableau d’OVR. En effet les OVR surviennent souvent la nuit a l’occasion du ralentissement circulatoire nocturne et sont ressenties le matin au reveil. L’OVR pourrait alors etre favorisee par l’hypoxie induisant une vasodilatation et aggravant le ralentissement circulatoire, et par l’augmentation de la pression intra-thoracique et intracrânienne qui retentit mecaniquement sur le nerf optique. De plus les reveils nocturnes repetes provoqueraient des poussees d’HTA aggravant des conditions circulatoires deja perturbees. D’autres effets peuvent agir comme l’augmentation de la coagulation par action sur l’agregabilite des plaquettes et sur les facteurs de coagulation, l’hyper activation du systeme sympathique, l’augmentation du stress oxydatif, de l’inflammation et l’apparition de dysfonctions endotheliales. Conclusion Ce travail decrit pour la premiere fois une association forte entre la presence d’une OVR et d’un SAS sur une serie de patients. Le syndrome d’apnee du sommeil pourrait probablement etre un facteur de risque supplementaire d’occlusion veineuse retinienne. Il serait probablement utile de rechercher systematiquement un SAS dans le bilan des OVR, d’autant qu’il existe des traitements efficaces de cette affection.

Forty-five patients who had primary cancer of the breast had a laparotomy when a second cancer appeared in the ovaries. There were no other peritoneal metastases to suggest that it was disseminated breast cancer. Twenty-eight had primary ovarian cancer and 17 metastases from breast cancer. The study comparing the two groups shows that: there are few clinical or paraclinical features that make it possible to arrive at a differential diagnosis; ovarian metastases occurring in patients who have primary breast cancer carry a more serious prognosis; if the cancer is a primary ovarian cancer (and not a secondary) the chances of survival are less poor; in primary ovarian cancer the results justify our attitude for carrying out surgery; screening systematically for ovarian involvement by using CA 125 or by routine ultrasound does not seem to us to be effective.

Four hundred and fifteen women, treated in our institution from 1961 to 1987 for operable carcinoma of the cervix stage I or II, had a radical hysterectomy with pelvic node dissection. Radiotherapy was associated with this surgery in most cases: 90% of the patients received endocavitary radiation, and 30% external radiotherapy, either pre- or post-operatively, in the case of bad prognostic factors. Median follow up was 7 years; overall survival was 77% at 10 years; the rate of local failure is low (36 cases/415 = 8.7%). Multifactorial analysis, using the Cox model, assessed the following independent prognostic factors, significant for the risk of local recurrence (size of the tumor, N +/- , FIGO stage) and for the risk of metastases and death (parametrium invasion, stage, tumor size). Post-operative mortality was 1.2%. Early surgical iatrogeny was easily treated with no long-term sequela, whereas severe complications, due to the association with pelvic irradiation, occurred in 24 out of 124 patients, leading to 7 "illegitimate" deaths.

Usually, the SBR histoprognostic grading is not considered appropriate for lobular invasive carcinoma. We previously demonstrated improved prognostic value of a modified SBR grading (MSBR) for invasive ductal carcinoma (IDC), specially when node negative. We did a multivariate analysis of 291 patients with operable, invasive, lobular breast carcinoma, to assess the prognostic value of the SBR/MSBR grading. We applied this MSBR to the studied population. The Cox multivariate analysis showed that the nodal status, clinical tumor size and MSBR were the three most important prognostic factors for DFS, and nodal metastasis, MSBR and progesterone receptor (PR) status for MFS. Indeed, we concluded that SBR grading is relevant for lobular invasive carcinoma, MSBR being more accurate, mainly because it discriminates grade II SBR patients. This result was not surprising as the pattern of ILC implicated a higher proportion of grade II SBR patients (78%), than IDC (55%).

When a locoregional recurrence of a cervical carcinoma occurs, the last hope from a curative surgical enterprise may be a pelvic exenteration. This procedure remains exceptional. Technically, it combines several standard resections of a number of pelvic organs, such as hysterectomy or colpectomy, partial or total cystectomy, perineectomy, bowel resections, lymphadenectomy.… But its specific application to each of these pelvectomies depends on the optimal process accorded to each particular patient, thereby strongly contrasting with the very codified treatment of initial disease. Using data from a historical series of 30 cases and the material from recent literature, we will try to define the reasonable frontiers to be maintained while undertaking the association of necessarily wide resections along with ambitious functional repairs (such as urinary and digestive continuity, conservation of sphyncteral control, vaginal replacement, filling of large pelvic losses…). The goal is a far from prohibitive 5 year-survival, from 15% globally to 50% in some rigorously selected series. Some mediocre results emphasize the need for evaluation of pejorative criteria, such as age, lateropelvic or upper urinary extensions, lymph node metastasis, or a short delay between initial treatment and relapse. Nevertheless, and however dramatic these conditions may turn out to be, some palliative indications can still be discussed: indeed, the outcome of a well-done exenteration may be considered less intolerable than unavoidable mechanical complications due to the cancerous propagation in itself.

1 Full reduction of the disulfide bridges of pure 19 S sheep thyroglobulin has been obtained by 2-mercaptoethanol in 0.1 M Tris-acetate pH 8.6 containing 8 M urea followed by alkylation (iodoacetate or iodoacetamide) of the thiol groups formed. 2 The S-carboxymethylderivative is soluble only in the presence of concentrated urea or guanidine hydrochloride. Dissolved in the presence of 5 M or 6 M guanidine at pH 7.0 or 8.6 it sediments in the ultracentrifuge as a single homogeneous boundary. 3 In 5 M or 6 M guanidine at 20° and 25° the sedimentation constants extrapolated to zero concentration are: s°20, guan 6 M= 1.2 S; s°25, guan 5 M= 2.0 S. The values for the diffusion constant and for the intrinsic viscosity are: D°25, guan 5 M= 3.4; 100 [η]20, guan 6 M= 85; 100 [η]25, guan 5 M= 78. 4 Using these values, 0.705 for v and the values of s/D determined by equilibrium or approach-to-equilibrium sedimentation, the following molecular weight have been calculated: M1= 80 × 103 or 85 × 103 (equilibrium sedimentation), M2= 81 × 103 (approach-to-equilibrium in 0.017 M SDS at pH 8.6), M3= 70 × 103 (Svedberg equation). The molecular weight computed from the values of s and [η] in 5M and 6M guanidine were 160 × 103 and 114 × 103 respectively. 5 By gel filtration on Sephadex G-200 in 0.1 M Tris-acetate pH 8.6 containing 0.017 M sodium dodecylsulphate, the S-carboxymethyl derivative of thyroglobulin is more retarded than γ-globulin 7 S and serumalbumin. After correction for protein-bound sodium dodecylsulphate the apparent molecular weight calculated for S-carboxymethyl thyroglobulin by gel filtration agrees fairly well with the molecular weight (80 × 103) computed from the hydrodynamic properties. A similar value has been obtained by gel filtration on Sephadex G-200 in Tris-acetate 0.1 M pH 8.6 containing 5 M guanidine. 6 The discrepancy between the values of the molecular weight computed from the measurements of s and [η] on the one hand and by the measurement of s/D or s and D on the other hand is discussed in relation to data in the literature. 7 It is concluded that the 12 S subunit of thyroglobulin is most probably constituted by two different peptide chains (A = B = 80 × 103) in a proportion which remains to be determined.

The records of 203 Cutaneous Malignant Melanomas treated at the Centre René Huguenin in Saint-Cloud from october, 1959 to december, 1978 were reviewed. The histologic data were reexamined and 155 cases were retained. Previously classified according to the histologic type and the invasion level of Clark, they were evaluated according to the thickness of the tumor by the ocular micrometer in 100 ths of a millimeter, as was done by Breslow. Other histologic data were collected for each case. Clinical and therapeutic informations and carcinologic events were gathered together. From this research, 155 cases were proved significant in accordance with Multifactorial Statistic Analysis. This study pointed out significant facts: 1) The thickness of the tumor is the utmost important factor, i.e. correlative with survival rate, recurrence and metastasis. 2) Starting with a short number of histologic and clinical variables it seems possible to draw a profile of a patient with cutaneous malignant melanoma and to obtain a precise prognosis and so prepare complementary treatment.

The records of 203 patients with cutaneous malignant melanoma treated at the Centre René Huguenin, Saint-Cloud, from october, 1959 to december, 1978 were reviewed. Histological data from 155 patients were retained after re-examination. The melanomas, which had previously been classified according to Clark's system of histological type and degree of invasiveness, were re-evaluated according to the thickness, were re-evaluated according to the thickness of the tumour as measured by Breslow's ocular micrometric method. Other histological data, as well as clinical and therapeutic data, were gathered together. One hundred and fifty cases were found to be suitable for standard single and multifactorial analysis, and 96 records contained sufficient information to be analyzed by the new "similarly aggregation" method developed by IBM. Two significant results emerged from the study: the thickness of the tumor is the single most important prognostic factor, as it correlates with the incidence of recurrences, metastases and deaths; by using a small number of clinical and histological variables, it seems possible to draw a profile of every new patient, to classify him in a well-determined prognostic category and, consequently, to institute a complementary treatment when needed.

The case of a 35-year-old primigravida with a 21-week intrauterine gestation and concurrent dysgerminoma of the ovary (stage Ic) is presented. A total hysterectomy with bilateral salpingo-oophorectomy was performed, followed by postoperative chemotherapy using cisplatin, bleomycin and vinblastine. The patient has done well since treatment, and is without evidence of recurrent disease 19 months later. Both radiation and chemotherapy are highly effective treatment modalities for dysgerminoma. For those patients with disease presenting in stages Ib, Ic, II and III who wish to maintain fertility, unilateral oophorectomy followed by combination chemotherapy may be curative and spare ovarian function.