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.

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.

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.

[Current situation of breast reconstruction after breast cancer in Reunion Island]. / État des lieux de la reconstruction mammaire après cancer du sein sur l'Île de la Réunion en 2016.

OBJECTIVES: The aim of this study is to describe the current trends of breast reconstruction (BR) and breast oncoplasty (BO) for breast cancer patients in Reunion Island. METHODS: This is a multicenter retrospective descriptive study of all BR and BO surgeries in 2016. We studied the first stage of BR that corresponds to the choice of surgical technique. Patient's age, care center, technique and duration of surgery, complications and their risk factors were reviewed. Patient satisfaction was assessed using the modified BREAST-Q©. RESULTS: In 2016, BR rate over total mastectomy was 47.6% and BO rate was 6.3% over partial mastectomy. Among the 92 patients included, 25 immediate BR were performed (84% in private institution) and 44 delayed BR (67% in public hospital). Although prosthetic techniques were the most used, satisfaction seems to be better with autologous techniques. CONCLUSIONS: The ratio of BR is high in Reunion Island with a wide range of techniques but uneven practice. Conversely, BO's ratio is low and improvement is needed.

Humoral and cellular immunity to RSV in infants, children and adults.

BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory disease throughout life. Here we report differences in naturally acquired immunity with age and presumed exposure. METHODS: A longitudinal, non-interventional, observational study was performed in healthy adults (20 paediatric healthcare workers and 10 non-healthcare workers), children (10 aged 3-6 years) and infants (5 aged 2-4 months and 20 aged 6-12 months). Blood samples were analysed for RSV-neutralising antibody titre, F/Ga/Gb-specific antibody titres, F-specific IgG/IgA memory B-cell frequencies and T-cell production of IFNγ, IL-4, IL-13 and IL-17. RESULTS: Serum G-specific antibody titres were significantly lower in infants and children than adults. However, serum titres of F-specific and RSV-neutralising antibody and IFNγ-producing T-cell frequencies were low or absent in the infants, but comparable between children and adults. Interestingly, F-specific memory IgA B-cells could not be detected in paediatric samples and in samples from non-healthcare workers, but recordable IgA memory B-cells were found in 9/18 paediatric healthcare workers and 2/8 non-healthcare workers at the end of the RSV season. These responses waned 4-6 months later. By contrast, F-specific IgG memory B-cells were detectable in samples from all adults without significant variation across time points. T-cells producing IL-4, IL-13 and IL-17 responses were not detectable in peripheral blood from a subset of volunteers. CONCLUSIONS: Repeated RSV exposure in early life generates immune responses that are inversely related to frequency of severe disease. Induction of F-specific antibody and cellular immune responses through infant vaccination might help to accelerate the development of protective immune responses at an early age. Clinicaltrials.gov reference NCT01563692 and NCT01640652.

Impact of completion axillary lymph node dissection in patients with breast cancer and isolated tumour cells or micrometastases in sentinel nodes.

BACKGROUND: Omission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion. METHODS: A retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts. FINDINGS: Among 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36-4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74-2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46-5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90-2.73). INTERPRETATION: A separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.

Evaluation of sentinel lymph node biopsy after previous breast surgery for breast cancer: GATA study.

AIM: Sentinel lymph node (SLN) biopsy was recently recommended after prior breast tumour surgery and lymphadenectomy is not the gold standard anymore for nodal staging after a lesion's removal. The purpose of our study was to evaluate the good practices of use of SLN biopsy in this context. PATIENTS AND METHODS: From 2006 to 2012, 138 patients having undergone a surgical biopsy without prior diagnosis of an invasive carcinoma with a definitive histological analysis in favour of this diagnosis were included in a prospective observational multicentric study. Each patient had a nodal staging following SLN biopsy with subsequent systematic lymphadenectomy. RESULTS: The detection rate of SLN was 85.5%. The average number of SLNs found was 1.9. The relative detection failure risk rate was multiplied by 4 in the event of an interval of less than 36 days between the SLN biopsy and the previous breast surgery, and by 9 in the event of using a single-tracer detection method. The false negative rate was 6.25%. The prevalence of metastatic axillary node involvement was 11.6%. In 69% of cases only the SLN was metastatic. The post-operative seroma rate was 19.5%. CONCLUSION: Previous conservative breast tumour surgery does not affect the accuracy of the SLN biopsy. A sufficient interval of greater than 36 days between the two operations could allow to improve the SLN detection rate, although further studies are needed to validate this statement. CLINICAL TRIAL REGISTRATION NUMBER: NCT00293865.

[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.

Occult cancer in specimens of reduction mammaplasty aimed at symmetrization. A multicentric study of 2718 patients.

Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%.

Rehabilitación dental y trastornos temporomandibulares en adolescentes de Puebla, México / Temporomandibular dental rehabilitation and adolescent disorders of Puebla, México

OBJETIVO: determinar el factor de riesgo para desarrollar trastornos temporomandibulares en adolescentes (TTM). METODOLOGIA: cohorte prospectiva realizada en 153 adolescentes, (52,9% mujeres y 47% hombres) libres de TTM. Para diagnosticar los TTM se utilizaron los Criterios Diagnósticos para la Investigación de los TTM (CDI/TTM), para determinar caries se aplicó el índice CPOD. Se formaron dos grupos, el grupo expuesto a rehabilitación dental (74), y el grupo no expuesto (79). Se realizaron seguimientos a las dos semanas, tres y seis meses de la rehabilitación dental. Se utilizó estadística descriptiva y se calculó el riesgo relativo con intervalos de confianza al 95%. Para el grupo de los expuestos, se incluyeron adolescentes libres de TTM en los que fue necesario realizar tratamiento de rehabilitación dental en órganos posteriores con caries en esmalte y dentina en fosas y fisuras. Para el grupo no expuesto, se incluyeron adolescentes pareados por edad y sexo con los expuestos, libres de TTM sin necesidades de rehabilitación dental. RESULTADOS : la incidencia de TTM a los quince días de los expuestos (18,9%) fue superior en contraste con los no expuestos (5,0%). El riesgo relativo de desarrollar TTM en los adolescentes rehabilitados con resina a las dos semanas posteriores a la rehabilitación fue de 2.412 (I.C. 95% 1.001-5,81) veces más que en aquellos que no fueron sometidos a la rehabilitación. CONCLUSION:la rehabilitación dental es un factor de riesgo mínimo para desarrollar TTM a corto plazo (15 días) de realizado el procedimiento, dicho padecimiento inducido por la rehabilitación dental es agudo y auto limitante.

OBJECTIVE: Determine the risk factor involved with developing temporomandibular disorders (TMD) in adolescents. METHODOLOGY: Prospective cohort study carried out on 153 TMD-free adolescents (52.9% women and 47% women). In order to diagnose TMDs the Diagnostic Criteria for Research into TMDs (CDI/TMD), and the CPOD index was used to determine cavities. Two groups were formed: one exposed to dental rehabilitation (74) and one group unexposed (79). Follow-ups were performed two weeks, three months and six months after dental rehabilitation. Descriptive statistics were used and the relative risk was calculated with confidence intervals at 95%. Included in the exposed group were TMDfree adolescents in whom it was necessary to carry out dental rehabilitation treatment on rear teeth with cavities using enamel and dentin to fill in pits and fissures. Included in the unexposed group were adolescents paired with the exposed group based on age and sex, TMD-free and without the need for dental rehabilitation. RESULTS :The incidence of TMD two weeks subsequently in the exposed group (18.9%) was greater in contrast with the unexposed group (5.0%). The relative risk of carrying out TMD on adolescents rehabilitated with resin two weeks after rehabilitation was 2.412 (C.I. 95% 1.001-5.81) times more than in those that did not undergo rehabilitation. CONCLUSION:Dental rehabilitation is a minimum risk factor for carrying out TMD in the short term (two weeks) after the procedure, as this disease induced by rehabilitation is acute and self-limiting.

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 tubular carcinoma of the breast and sentinel lymph node biopsy: a retrospective multi-institutional study of 234 cases.

BACKGROUND: Pure Tubular Carcinoma (PTC) of the breast is a rare histological subtype of invasive breast cancer characterized by a low rate of lymph node involvement. Currently there is no consensus on less surgical axillary node staging according to this histological subtype. METHODS: We performed a retrospective multi-institutional study. Inclusion criteria were PTC, sentinel lymph node detection (SLND) and conservative breast surgery. RESULTS: From January 1999 to December 2006, 234 patients were included in the study from 9 institutions. The median pathological tumor size was 9.59 (1-22) mm. SLN were successfully detected in 98% (229/234) of patients. Among the 234 patients, a macrometastasis was found in 6 cases (2.5%), micrometastasis in 15 cases (6.4%), and isolated cells in 2 cases (0.8%). In the case of patients with SLND macrometastasis, half of them had macrometastasis in the complementary axillary lymphadenectomy, and none in the case of SLN only micrometastasis or isolated cells. Of the 122 patients with a pathological tumor size <10 mm, none had sentinel node macrometastasis. According to a multivariate analysis, pathological tumor size (>10 mm) was the only parameter significatively linked to the risk of lymph node involvement (p = 0.007). CONCLUSION: In a large multi-institutional series with SLND, we have shown that the risk of axillary lymph node involvement in PTC is very low. In the case of PTC <10 mm, we suggest that surgical axillary evaluation, even with SLND, may not be warranted.

The inflammatory breast: management, decision-making algorithms, therapeutic principles.

Inflammatory syndrome is one of the rare emergency breast situations. Its etiology is benign, infectious in most cases. The clinical examination is often self-evident and suggests the diagnosis. But alone it is insufficient, and diagnostic tests are necessary to guide therapy. As essential as it is, mammography's limitations reinforce the benefit of ultrasonography, which in all cases reveals an abscess and has greater sensitivity for detecting a malignant tumor. If the etiology is benign, clinical signs will disappear with medical treatment, with no need for further investigation. While it is legitimate to initiate a trial treatment, it must not delay oncologic management, because of the severity of inflammatory cancer.

[Hodgkin's disease and breast cancer: for which patients is there an association? A series from Institut Bergonié]. / Maladie de Hodgkin et cancer du sein: une association pour quelles patientes ? À propos d'une série de l'institut Bergonié

OBJECTIVE: Breast cancer is the most frequent secondary tumor for women treated for Hodgkin's disease. It is important to study the risk factors associated to be able to adapt the monitoring of these women. PATIENTS AND METHODS: This is a retrospective study from Institut Bergonié, a comprehensive French Cancer Center, concerning the women treated for Hodgkin's disease and having developed a breast cancer. RESULTS: Among 328 women treated for Hodgkin's disease between January 1968 and December 1994, 20 patients developed 25 breast cancers. The average age of the patients during the irradiation was 24 years and the average period of occurrence of the cancer was 19 years. An irradiation of the chest wall and an under-diaphragmatic irradiation in doses of 40Gy are risk factors for the occurrence of breast cancer. A young age, less than 30, in the treatment of Hodgkin's disease tend to be significant. DISCUSSION AND CONCLUSION: This population of women with a high risk of breast cancer thus has to benefit from an appropriate monitoring program, which is what we suggest setting up in the Institut Bergonié.

Tryptophan hydroxylase(2) gene polymorphisms predict brain serotonin synthesis in the orbitofrontal cortex in humans.

Brain regional serotonin synthesis can be estimated in vivo using positron emission tomography (PET) and α-[((11))C]methyl-L-tryptophan ((11)C-AMT) trapping (K*) as a proxy. Recently, we reported evidence of lower normalized (11)C-AMT trapping in the orbitofrontal cortex (OBFC) of subjects meeting the criteria for an impulsive and/or aggressive behavioral phenotype. In this study, we examined whether part of the variance in OBFC serotonin synthesis is related to polymorphisms of the gene that encodes for the indoleamine's rate-limiting enzyme in the brain, tryptophan hydroxylase-2 (TPH(2)). In all, 46 healthy controls had PET (11)C-AMT scans and were genotyped for 11 single-nucleotide polymorphisms (SNPs) distributed across the TPH(2) gene and its 5' upstream region. Several TPH(2) SNPs were associated with lower normalized blood-to-brain clearance of (11)C-AMT in the OBFC. Dose-effect relationships were found for two variants (rs6582071 and rs4641527, respectively, located in the 5' upstream region and intron 1) that have previously been associated with suicide. Associations in the OBFC remained statistically significant in a mixed larger sample of patients and controls. These results suggest that in humans, genetic factors might partly account for variations in serotonin synthesis in the OBFC.

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.

Phase III randomized equivalence trial of early breast cancer treatments with or without axillary clearance in post-menopausal patients results after 5 years of follow-up.

BACKGROUND: Axillary lymph node clearance (ALNC) improves locoregional control and provides prognostic information for early breast cancer treatment, but effects on survival are controversial. This multicentre, randomized pragmatic equivalence trial compares outcomes for post-menopausal early invasive breast cancer patients after locoregional treatment with ALNC and adjuvant therapies to outcomes after locoregional treatment without ALNC and adjuvant therapies. METHODS: From 1995-2005, women aged ≥ 50 years with early breast cancer (tumor ≤ 10 mm) and clinically-negative axillary nodes were randomized to receive treatment with ALNC (Ax) or without (no-Ax). Adjuvant therapies were prescribed according to hormonal receptor status and individual histological results. The primary endpoint was overall survival (OS); secondary endpoints were event-free survival (EFS) and functional outcomes. The trial was terminated due to lack of equivalence and low accrual after first interim analyses. TRIAL REGISTRATION: NCT00210236. RESULTS: Of 625 patients, 297 no-Ax and 310 Ax patients were maintained for final per-protocol analyses. OS and EFS at five years were not equivalent (Ax vs. no-Ax: 98% vs. 94% and 96% vs. 90% respectively). Recurrence was higher for no-Ax, particularly in the first five years after surgery. Axillary nodes were positive for 14% Ax patients but only 2% no-Ax patients experienced axillary node recurrence. Functional impairments were greater after ALNC. CONCLUSION: Our results fail to demonstrate equivalence of outcomes when ALNC is omitted from post-menopausal early breast cancer patient treatment. However the low locoregional recurrence rates warrant further examination over a longer duration, in particular to consider whether these would impact on survival.

Ductal carcinoma in situ of the breast in younger women: a subgroup of patients at high risk.

BACKGROUND: After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS. METHODS: From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy. RESULTS: 37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype (p = 0.004), histological size more than 10 mm (p = 0.011), necrosis (p = 0.022) and positive margin status (p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%. CONCLUSION: High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free.

[Ductal carcinoma in situ of the breast (DCIS). Histopathological features and treatment modalities: analysis of 1,289 cases]. / Carcinomes canalaires in situ (CCIS). Caractéristiques histopathologiques et traitement : analyse de 1 289 cas.

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.