Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study.

BACKGROUND: We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors. PATIENTS AND METHODS: We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the Kaplan-Meier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients. RESULTS: LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients [hazard ratio (HR) = 1.345, HR = 1.312, and HR = 1.415, respectively; P < 0.0001], which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with AC-treated luminal A-like tumors. CONCLUSION: The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy.

Real-time precise microfluidic droplets label-sequencing combined in a velocity detection sensor.

Droplets microfluidics is broadening the range of Lab on a Chip solutions that, however, still suffer from the lack of an adequate level of integration of optical detection and sensors. In fact, droplets are currently monitored by imaging techniques, mostly limited by a time-consuming data post-processing and big data storage. This work aims to overcome this weakness, presenting a fully integrated opto-microfluidic platform able to detect, label and characterize droplets without the need for imaging techniques. It consists of optical waveguides arranged in a Mach Zehnder's configuration and a microfluidic circuit both coupled in the same substrate. As a proof of concept, the work demonstrates the performances of this opto-microfluidic platform in performing a complete and simultaneous sequence labelling and identification of each single droplet, in terms of its optical properties, as well as velocity and lengths. Since the sensor is realized in lithium niobate crystals, which is also highly resistant to chemical attack and biocompatible, the future addition of multifunctional stages into the same substrate can be easily envisioned, extending the range of applicability of the final device.

Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort☆.

BACKGROUND: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm. PATIENTS AND METHODS: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status. RESULTS: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS. CONCLUSION: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0.

Solitonic waveguide reflection at an electric interface.

A refractive index interface is dynamically induced in a bulk photorefractive material by biasing two adjacent regions with different electric fields, thus building up an electric wall. Effects of this interface on reflection, refraction and breathing of bright photorefractive solitons and their associated waveguides are numerically and experimentally studied as a function of the induced purely electric field gradient. Reflection and refraction efficiency depends on the amplitude and sign of the applied voltages that affect both the self-confining beam and the signals propagating inside the waveguide. Experimental tests are performed in nominally undoped lithium niobate samples.

Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study.

PURPOSE: GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone. RESULTS: From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3-17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed. CONCLUSION: In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

Actividad física y hábito tabáquico en estudiantes adolescentes / Physical activity and smoking habit in adolescent students

El objetivo de este estudio fue detectar en qué medida afecta la actividad física y el hábito tabáquico en estudiantes de Enseñanza Secundaria. Se estudiaron 168 adolescentes no fumadores y fumadores recién iniciados. Se midieron peso, talla, presión arterial, frecuencia cardíaca, actividad física, fuerza, flexibilidad y resistencia y una prueba espirométrica. Tanto en chicas y chicos fumadores, se evidenciaron peores resultados en la mayoría de los parámetros espirométricos (FEV1, FEF25-75%, FVC) y un envejecimiento prematuro del pulmón, más acentuado en chicas. La actividad físico-deportiva moderada se asocia a adolescentes que menos fuman y tienen más facilidad para abandonar el hábito tabáquico (AU)

The aim of the study was to detect how physical education and smoking habits affect secondary school students, 168 non smokers and newly initiated were studied. Weight, height, heart rate, blood pressure, physical activity, strength, flexibility and endurance, and spirometric tests were analyzed. In both, female and male smokers, obtained worse results in the mayority of spirometric parameters (FEV1, FEF25-75%, FVC) and premature lung ageing, more pointed in females. Moderate physical-sporting activity is associated to adolescents who smoke less and quit smoking more easily (AU)

Nipple sparing mastectomy for breast cancer is associated with high patient satisfaction and safe oncological outcomes.

BACKGROUND: The preservation of the nipple areolar complex (NAC) for cancer treatment is still a matter of debate because of suspected increase of local recurrence and surgery-specific complications. The aim of the study was to investigate both the relapse risk associated with nipple sparing mastectomy (NSM) for breast cancer and women's satisfaction with preservation of the NAC. METHODS: We included retrospectively all patients who had skin-sparing mastectomy (SSM) or NSM from 2007 to 2012 for breast cancer or ductal carcinoma in situ (DCIS). We compared NSM and SSM group for oncological and surgical outcomes. Patients' satisfaction and quality of life has been evaluated by a specifically designed questionnaire. RESULTS: We included 63NSM (41.5%) and 89SM (58.5%). Eighty-nine (58.6%) patients had DCIS, and the other had small invasive disease. Median follow-up was 42 (IQR: 18-58) months. Local recurrence rate was 1.7% (n=1) in the NSM group and 0% in the SSM group without recurrence in the preserved nipple. After NSM, one patient had complete NAC necrosis, and three patients suffered partial necrosis. Satisfaction with the NAC was higher in the NSM group compared to the SSM group with delayed reconstruction of the nipple (75% vs. 59%, P=0.14). Patients with NSM required less psychological support before (P=0.028) and immediately after surgery (P=0.14) than patients in the SSM group. CONCLUSION: NSM can successfully and safely be performed for pre-invasive and small invasive breast cancer. Besides esthetic aspects, preserving the nipple may ease the acceptance of these radical form of surgery.

Voltage-induced waveguides in lithium niobate films on silicon substrates.

Electrically tunable channel waveguides have been fabricated by domain inversion of a LiNbO3 thin film bonded to a silicon wafer. The electro-optic effect is used to induce the waveguides and to alter its guiding properties. A low amplitude electric signal can tune the voltage-induced structure from an efficient waveguide to an antiguide giving a waveguide transmission that varies over more than 25 dB. The frequency response of the components is given.

Low drive voltage electro-optic Bragg deflector using a periodically poled lithium niobate planar waveguide.

An electro-optic Bragg light deflector is demonstrated in a thinned, periodically poled lithium niobate planar waveguide confined between two silica layers on a silicon substrate. More than 97% of diffraction efficiency is obtained with an operating wavelength of 633 nm for the two orthogonal light polarizations with a drive voltage of about 5 V. The temporal electric drift and the response time of the component are also studied.

[Lobular invasive breast cancer prognostic factors: About 940 patients]. / Facteurs pronostiques des carcinomes lobulaires infiltrants du sein : à propos de 940 cas.

OBJECTIVES: To assess the prognostic factors of T1 and T2 infiltrating lobular breast cancers, and to investigate predictive factors of axillary lymph node involvement. METHODS: This is a retrospective multicentric study, conducted from 1999 to 2008, among 13 french centers. All data concerning patients with breast cancer who underwent a primary surgical treatment including a sentinel lymph node procedure have been collected (tumors was stage T1 or T2). Patients underwent partial or radical mastectomy. Axillary lymph node dissection was done systematically (at the time of sentinel procedure evaluation), or in case of sentinel lymph node involvement. Among all the 8100 patients, 940 cases of lobular infiltrating tumors were extracted. Univariate analysis was done to identify significant prognosis factors, and then a Cox regression was applied. Analysis interested factors that improved disease free survival, overall survival and factors that influenced the chemotherapy indication. Different factors that may be related with lymph node involvement have been tested with univariate than multivariate analysis, to highlight predictive factors of axillary involvement. RESULTS: Median age was 60 years (27-89). Most of patients had tumours with a size superior to 10mm (n=676, 72%), with a minority of high SBR grade (n=38, 4%), and a majority of positive hormonal status (n = 880, 93, 6%). The median duration of follow-up was 59 months (1-131). Factors significantly associated with decreased disease free survival was histological grade 3 (hazard ratio [HR]: 3,85, IC 1,21-12,21), tumour size superior to 2cm (HR: 2,85, IC: 1,43-5,68) and macrometastatic lymph node status (HR: 3,11, IC: 1,47-6,58). Concerning overall survival, multivariate analysis demonstrated a significant impact of age less than 50 years (HR: 5,2, IC: 1,39-19,49), histological grade 3 (HR: 5,03, IC: 1,19-21,25), tumour size superior to 2cm (HR: 2,53, IC: 1,13-5,69). Analysis concerning macrometastatic lymph node status nearly reached significance (HR: 2,43, IC: 0,99-5,93). There was no detectable effect of chemotherapy regarding disease free survival (odds ratio [OR] 0,8, IC: 0,35-1,80) and overall survival (OR: 0,72, IC: 0,28-1,82). Disease free survival was similar between no axillary invasion (pN0) and isolated tumor cells (pNi+), or micrometastatic lymph nodes (pNmic). There were no difference neither between one or more than one macromatastatic lymph node. But disease free survival was statistically worse for pN1 compared to other lymph node status (pN0, pNi+ or pNmic). Factors associated with lymph node involvement after logistic regression was: age from 51 to 65 years (OR: 2,1, IC 1,45-3,04), age inferior to 50 years (OR 3,2, IC: 2,05-5,03), Tumour size superior to 2cm (OR 4,4, IC: 3,2-6,14), SBR grading 2 (OR 1,9, IC: 1,30-2,90) and SBR grade 3 (OR 3,5, IC: 1,61-7,75). CONCLUSION: The analysis of this series of 940 T1 and T2 lobular invasive breast carcinomas offers several information: factors associated with axillary lymph node involvement are age under 65 years, tumor size greater than 20mm, and a SBR grade 2 or 3. The same factors were significantly associated with the OS and DFS. The macrometastatic lymph node involvement has a significant impact on DFS and OS, which is not true for isolated cells and micrometastases, which seem to have the same prognosis as pN0.

Characteristics and clinical outcome of T1 breast cancer: a multicenter retrospective cohort study.

BACKGROUND: A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST). PATIENTS AND METHODS: Retrospective analysis of all patients with T1 BC, who underwent surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized. RESULTS: Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11-15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors. CONCLUSION: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.

Pure flat epithelial atypia: is there a place for routine surgery?

PURPOSE: To determine whether it is appropriate to routinely undertake surgery if flat epithelial atypia (FEA) or pure flat epithelial atypia (pFEA) is found on large-core biopsy. PATIENTS AND METHODS: Between 2005 and 2010, 1678 large-core biopsy procedures were carried out, which led to 136 FEA sites being identified, 63 of which across 59 patients were pFEA (four patients had two sites of pFEA each). Forty-eight patients underwent further surgical excision, equating to 52 excised sites of pFEA. RESULTS: Of the 52 operated sites, there were 20 benign lesions (38%), 26 borderline lesions (56%), and three ductal carcinomas in situ (6%). The rate of histologic underestimation was put at 3.8%. Of the three cases that were underestimated, one was discarded because the definitive histology was not representative of the site from which microcalcifications had initially been taken. The other two cases that were underestimated were found in patients with an increased individual risk of breast cancer. CONCLUSION: In patients with no personal or first-degree family history of breast cancer, after complete or subtotal excision under radiology of the radiological lesion, and while excluding images fitting BI-RADS 5, annual monitoring may be offered as an alternative to surgical excision in view of the absence of underestimation found in our study.

Cost comparison of axillary sentinel lymph node detection and axillary lymphadenectomy in early breast cancer. A national study based on a prospective multi-institutional series of 985 patients 'on behalf of the Group of Surgeons from the French Unicancer Federation'.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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]. CONCLUSION: 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.

[Intraoperative molecular assessment of sentinel nodes in the breast cancer using the Gene Search BLN Assay technique: our experience about 126 patients]. / Évaluation de l'analyse peropératoire des ganglions "sentinelle" par biologie moléculaire (technique Gene Search BLN Assay) dans le cancer du sein: à propos de 126 patientes.

INTRODUCTION: Intraoperative molecular assay Gene Search BLN Assay (BLN) detects sentinel lymph node (SLN) metastasis in breast cancer. Our objective was to compare BLN to the definitive conventional histologic methods and to experiment the management of BLN in routine. MATERIAL AND METHODS: Each SLN was cut into alternate slabs. Half slabs were analysed with the intraoperative BLN molecular method, and the other slabs with the definitive histologic method. RESULTS: Two hundred and thirty four SLN have been analysed (124 patients). Thirty-five SLN had metastasis for 29 patients (23.4%). BLN correctly identified 28 patients. Two cases of discordance between BLN and standard method were found, probably explained by a sample bias. The sensibility of BLN is 96.4%, the sensitivity is 99%, the predictive positive value is 96.4%, the predictive negative value is 99% and the concordance is 98.4%. The surgery time increases and there is a need to adapt the theatre organization accordingly. CONCLUSION: The Gene Search BLN Assay gives a great interest for the patient, the surgeon and the pathologist because it increases the quality of the intraoperative analysis by comparison with the intraoperative conventional histology.

[Radiotherapy and combined therapy in breast cancer: standards and innovations in the adjuvant setting]. / Radiothérapie et associations thérapeutiques dans le cancer du sein: actualités et innovations en situation adjuvante.

Due to the significant advances in the diagnosis and treatment of breast cancer seen in the last decades, increased survival rates and better outcomes of patients are being observed. The role of radiotherapy remains pivotal in the treatment of early breast cancer. In the adjuvant setting, whole breast irradiation remains the standard of care using a relatively well standardized radiation technique. The recent technology advances and 3D conformal radiotherapy allow for better volumes definition resulting to increased organ at risk--sparing and therefore treatment optimization. Sophisticated techniques and emerging options (such as accelerated partial breast irradiation) are not routinely used yet outside of a clinical trial. Moreover, new drugs and targeted therapies have recently been introduced to the clinical practice for treatment individualization according to the specific tumours' prognosis and/or prediction of the drugs' efficacy based on new biological tools. Regarding the synergistic effect of these molecules with ionizing radiation, rigorous prospective evaluation of combined therapy is important to ensure improved long-term benefit/risk ratio. In this review, the significant advances of radiotherapy and combined therapy in the new era of breast cancer management will be discussed.