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Unlabelled: The aim of this study was to compare the effectiveness of a hand-held preoperative compact imager (POCI) camera with conventional lymphoscintigraphy using a γ-camera for sentinel lymph node (SLN) detection in breast cancer., Methods: The main objective was to demonstrate the noninferiority of the POCI relative to conventional lymphoscintigraphy and to compare the number of SLNs detected by the 2 imaging devices. Our study, a clinical prospective, double-blind, noninferiority study, planned to include 200 patients with early breast cancer and started in January 2006. A standard SLN protocol (4 periareolar injections of 37 MBq of (99m)Tc-nanocolloids, 2 h before lymphoscintigraphy) was performed preoperatively using a conventional γ-camera and then the POCI camera. Scans were obtained by 2 different nuclear medicine physicians unaware of each other's results. The day after, in the operating room, the surgeon, after receiving the previous results, used the counting probe for surgical SLN biopsy. The number and localization of axillary SLNs obtained by lymphoscintigraphy and the POCI and the duration of the whole procedure were determined., Results: Among the 162 patients included, 138 were evaluable. The POCI detected more SLNs than did lymphoscintigraphy in 50 patients (36%), the same number of in 54 patients (39%), and fewer SLNs in 34 patients (25%), representing 84 (61%) discordant pairs. The noninferiority of preoperative compact imaging of axillary SLNs numbers was found to be statistically significant (95% confidence interval, 30%-52%, P = 0.025) using the McNemar test. The duration of acquisition was shorter using the POCI (<10 min in 84% [n = 117] of patients; mean, 7.5 ± 3.3 min) than lymphoscintigraphy (13% [n = 18] of patients; mean, 15.7 ± 3.4 min), with P < 0.001 using the McNemar test for paired proportions., Conclusion: Preoperative compact imaging using a hand-held camera was able to predict the number and localization of breast cancer SLNs and was not inferior to conventional lymphoscintigraphy in this study. Further studies will determine whether preoperative compact imaging could replace lymphoscintigraphy, especially in surgical centers without an on-site nuclear medicine department.

In breast conserving surgery (BCS), the usefulness to perform systematic cavity shaving is actively debated. Some investigators argued that systematic cavity shaving could avoid surgical re-excision and make diagnosis of unexpected multifocality. Others argued that usefulness of cavity shaving depends on volumes of resection. In this study one hundred patients undergoing BCS with systematic cavity shaving were included. Margins less than 3 mm were considered to be insufficient. We tested clinico-pathological characteristics in order to identify predictive model of cavity margin shaving utility and we sought to determine if cavity margin shaving usefulness depends on volumes of resection. We showed that cavity shaving avoids the need for re-excision in 24% of cases as well as diagnosis of multifocality in 6% of cases. However, the clinical usefulness of cavity shaving was not related to the volumes of resection., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to determine the chemosensitivity of pregnancy-associated breast cancer (PABC) in the neoadjuvant setting by comparing the observed pathological complete response (pCR) rate with the rate predicted by a validated nomogram., Methods: Data from 48 PABC patients who received neoadjuvant chemotherapy (NACT) were collected. To predict the response rate to chemotherapy, we used well-calibrated logistic regression-based nomograms to calculate individual probability of pCR., Results: Observed rates of pCR were concordant with predictions in the whole sample and in the analyzed subgroups. For the whole sample, the area under the receiver-operated curve (AUC) was 0.77 (95% CI 0.66-0.87). The calibration of predicted and observed probabilities was excellent. In the subgroup analyses (NACT initiated during pregnancy or postpartum, NACT with only anthracycline or both anthracycline and taxanes), discriminations assessed by AUC were significantly above 0.5, except for patients treated with anthracycline only. The interpretation was limited by a lack of power., Conclusion: Through the use of nomograms, our study demonstrates that PABC is as chemosensitive as non-PABC and suggests that taxanes should be part of the NACT regimen for PABC. Further studies are warranted to increase the power of the presented data.

Objectives: Multicentricity is not listed as a major prognostic parameter in invasive breast carcinoma, and is not by itself an indication of systemic adjuvant treatment. Furthermore, evaluating the size of these tumors is discussed. The aims of this study are to evaluate prognostic value of multicentricity, and to compare different way for measuring multicentric breast carcinomas., Patients and Methods: Between 2001 and 2008, 1458 patients having breast invasive carcinoma were included in Tenon Hospital, Paris, France; 16% had a multicentric cancer. We have compared impact of multicentricity on lymph node (LN) involvement, and compared 3 ways for measuring these cancers., Results: LN involvement was significantly associated with multicentricity. We found an over-risk of 20% for LN involvement in patients having multicentric cancer, whatever the size of the tumors. Considering the diameter of the largest focus is the best way for measuring these cancers., Discussion and Conclusion: We did not find a subgroup of patients at low risk of LN involvement when having a multicentric breast cancers. These results lead us to extend indications of adjuvant chemotherapies in all multicentric breast cancer. These results should be validated by randomized prospective studies., (Copyright © 2011. Published by Elsevier SAS.)

Purpose: Estrogen receptor-positive (ER+) and -negative (ER) breast cancers are molecularly distinct diseases. We hypothesized that p53 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of cancers., Experimental Design: We developed a 39-gene p53 signature derived from 213 ER+ and a separate 30-gene signature from 38 ER- cancers with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and ER- cancers, respectively., Results: External validation to predict p53 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant metastasis free survival in ER+ cancers in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant tamoxifen therapy (n = 277, HR = 2.43, P < 0.0001) but it was not prognostic in ER- cancers. It was also associated with higher chemotherapy sensitivity in ER+ but not in ER- cancers. The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER-, p53 signature showed no prognostic or predictive values in ER+ cancers but it was associated with better prognosis in ER- cancers. It also had no chemotherapy response predictive value in ER- or ER+ cancers., Conclusions: P53 dysfunction is prognostically most relevant in ER+ cancers and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of breast cancer., (©2011 AACR.)

ADN ploidy was shown to play a role in genomic instability of cancer cells and prognosis. The implication of the centrosome in the cell cycle was also described. Therefore, new prognostic factors could be suggested for a better-tailored therapy. The purpose of this study is to search for correlation between centrosomal abnormality and ADN ploidy in breast cancer. Cell prints were prepared from cell culture of mesothelial ascitis, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Fresh cell prints were also obtained from cases with invasive carcinoma. The centrosome was labelled by an indirect immunofluorescence assay using anti-γ-tubulin antibody and F(ab')(2) FITC before quantification with fluorescence microscopy. ADN ploidy was scored with DNA index obtained by means of flux cytometry. The normal mesothelial cells (94% of cells with only one centrosome) and the diploid cell line MRC5 (68% of cells with two centrosomes) were used as controls. DNA ploidy was found to be correlated with centrosomal abnormality in MCF7 cell line (64% of cells had more than three centrosomes) but not in the 10 cases of invasive ductal carcinoma analysed in this study. The absence of correlation between DNA ploidy and centrosomal abnormality in breast cancer samples may be due to the small numbers of cases, the cell prints or tumorigenesis. Correlation analysis of a larger number of cases and types of breast lesions to numerical and morphological abnormalities of the centrosome are ongoing.

Introduction: Adjuvant treatments are usually decided according to guidelines. However, many individual factors, such as performance status, patient refusal, complex interactions between factors (eg, discrepancies between grade and Ki 67), and complex clinical features (borderline age or tumor size) may introduce discrepancies. The aim of this study was to quantify discrepancies between local guidelines and patient management., Patients and Methods: From 2003 and 2005, 581 consecutive patients underwent surgery for invasive breast cancer. Patient, tumor characteristics, and outcome were recorded. We compared patient characteristics according to whether local guidelines had been followed., Results: In 90% of cases local guidelines were followed. Patients who inadequately did not receive chemotherapy were older (P < .0001), with positive hormonal receptor status (P = .02), and less aggressive tumors (P < .05). Main reasons for not administering chemotherapy were age, patient refusal, and micrometastatic node involvement. Patients from the other discordant group (ie, those who inadequately received chemotherapy), had larger (P = .01) and more aggressive tumors (P < .0001). In these cases, the clinical decision was mainly based on multifocal tumors and limit lower age. For disease-free survival (DFS), we found a significant difference between groups (P = .001). The best overall survival and DFS was found for patients who adequately received no adjuvant treatment. Survival among groups were similar when stratified on treatment modality., Conclusion: The main reasons for discrepancy were age (advanced or lower limit), patient refusal, and multifocal tumors. In this series, deviations from recommendations had no affect on survival and raised the question of new indications for chemotherapy such as multifocal tumors.

The sentinel lymph node (SLN) procedure is now used routinely for the staging of clinically node-negative patients with early breast cancer. Two identification techniques exist: colorimetric and isotopic. These can be used alone or in combination. The combined method is associated with an increased identification rate. However, allergic and adverse reactions to blue dyes have been reported. The objective of this review was to determine the incidence of such events and to discuss alternative approaches. The authors conducted a search of the MEDLINE and EMBASE databases for reports of anaphylactic responses to isosulfan blue dye and patent blue V dye. Allergic reaction to the dyes isosulfan blue and patent blue V is rare and the reported incidence varies between 0.07% and 2.7%. Methylene blue dye appears to be safer, with no cases of allergic events having been reported. However, allergy tests in some patients have proven that there is cross-reactivity between isosulfan blue dye and methylene blue dye. Even though the risk of an anaphylactic response is low, this raises questions about the usefulness of colorimetric detection of SLN and whether alternatives to the use of the isosulfan and patent blue V dyes, such as methylene blue, exist., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Introduction: Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy., Materials and Methods: Our dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype., Results: The interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031) of positive sentinel node biopsy than the ER status by itself (p = 0.016). A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72) and calibration (HL p = 0.28/0.05/0.11) in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated., Discussion: We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.

Multifocality in breast cancer is a frequent phenomenon, whose prevalence may vary between 13 and 75%. The differences in estimation of the prevalence of multifocality across studies may be explained by the differing definitions used for multifocality and multicentricity; this inconsistency makes it difficult to analyze the literature on the subject. The incidence of multifocality is probably often underestimated. Currently, the diagnosis relies on imaging. The performance of mammography is relatively low, but the addition of breast ultrasonography can improve diagnostic sensitivity. Recently, breast magnetic resonance imaging (MRI) has been shown to be more accurate for detecting multifocality compared to conventional imaging. However, this modality is associated with high rates of false-positives that could result in inappropriate disease management. Thus, the use of MRI is not recommended as a first-line technique for diagnosing multifocality. The diagnosis of multifocality is important for breast cancer management, particularly with regards to the choice of surgery. A finding of multifocality may spur a decision to perform a wider excision that will avoid positive margins. Regarding the results of conservative surgery in the presence of multifocality, studies are contradictory, and no international consensus exists. Multifocality may also modify the management of the axillary basin; studies have shown that multifocality is associated to an over-risk of 20% of lymph node invasion. The sentinel node biopsy has been considered as an alternative to complete axillary lymph node dissection by the American Society of Clinical Oncology. The prognostic value of multifocality is still not well known, although some studies have suggested that it is associated with a worst prognosis. Further studies are needed to better assess the impact of multifocality on breast cancer prognosis., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: The therapeutic role of lymphadenectomy on the survival in patients with ovarian cancer is controversial. The aim of this study was to evaluate the survival impact of lymphadenectomy, depending on the disease stage and extent of the surgery., Design: The surveillance, epidemiology, and end results (SEER) registry provided ovarian cancer data from 17 registries., Setting: Surveillance, Epidemiology, and End Results database., Population: The study population comprised 49,783 patients., Methods: Survival was studied according to the number of lymph nodes removed, with stratifications on disease stage and extent of surgery., Main Outcome Measure: The 5-year cause-specific survival rate., Results: The median follow up for patients alive at the last follow-up visit was 39 months. The five-year cause-specific survival rates were 37, 62, and 71% for the groups in which no lymph nodes were examined, in which between one and nine nodes were examined, and in which ten or more nodes were examined, respectively (P< 0.001). Avoiding lymphadenectomy was deleterious in all stages of the disease. It was maximal for International Federation of Gynecology and Obstetrics (FIGO) stage-II patients, but there was no significant interaction between stage and extent of lymphadenectomy. The cause-specific survival was found to significantly increase when more nodes were resected, even if the surgical procedure consisted of debulking surgery or a pelvic exenteration., Conclusion: Our study suggests a beneficial effect of lymphadenectomy in epithelial ovarian tumours, regardless of the stage of disease and extent of surgery. However, potential biases inherent to this retrospective methodology, such as staging migration, defining the extent of residual disease, and the possibility that thorough lymphadenectomy may reflect the quality of cytoreductive surgery, preclude any formal conclusions on the therapeutic role of lymphadenectomy., (© 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.)

Objective: Experimental data have revealed the critical role played by 2-methoxy-estradiol, a metabolite of 17β-estradiol, in the pathophysiology of preeclampsia. We used gas chromatography/mass spectrometry to measure a whole panel of hormonal steroids in the plasma from women during the third trimester of their pregnancy., Study Design: The population study consists of 24 pregnant patients with different outcomes: normal, or complicated by isolated preeclampsia or by severe preeclampsia with Hemolysis Enzyme Liver Low Platelets (HELLP) syndrome., Results: 17β-estradiol was reduced by 50% in isolated preeclampsia, and by 70% in severe preeclampsia with HELLP syndrome (normal: 8.54 ± 0.9 ng/mL; isolated preeclampsia: 4.65 ± 1.0 ng/mL; severe preeclampsia with HELLP syndrome: 2.64 ± 0.4 ng/mL), as is estrone. Downstream, 2-methoxy-estradiol was decreased only in severe preeclampsia with HELLP syndrome. The concentrations of estrone and 17β-estradiol precursors were comparable between groups, suggesting that placental aromatase is deficient in preeclampsia., Conclusion: The gradual decrease of estrogen levels with increasing severity of preeclampsia suggests an impairment of placental steroidogenesis., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Breast cancer is a frequent and heterogeneous disease. The choice of systemic treatments such as chemotherapy is based on predicting factors of response that did not much evolve. Preoperative chemotherapy provides an opportunity to directly assess tumor response to therapy. Predictors based on mathematical models could optimize those treatments. To go on this way, three different concepts have been developed to predict the preoperative chemotherapy complete response. Predictors based on clinical and pathological variables are specific of a tumor. They combine into mathematical models variables that have been previously identified as predicting the preoperative chemotherapy complete response. Predictors based on gene expression profile have been developed from groups of patients who received preoperative chemotherapy. They integrate multigene information to predict the tumor behaviour in front of several cytotoxic agents. Those predictors developed for each type of drug characterize the genetic chemoresistance of a tumor. In the same time, predictors of chemosensitivity developed from cell lines of diverse human cancer appeared. The authors established a genetic profile involved into chemoresistance and extrapolated the drug sensitivity for another type of cancer which was not represented, as breast cancer. All those predictors seem interesting but evolution of patients' characteristics and treatments induces a perpetual reassessment to optimize our predictive abilities., (Copyright 2010. Published by Elsevier SAS.)

PURPOSE Brain metastasis is usually a fatal event in patients with stage IV breast cancer. We hypothesized that its occurrence can be predicted if a clinical nomogram can be developed, thus allowing for selection of enriched patient populations for prevention trials. PATIENTS AND METHODS Electronic medical records of patients with metastatic breast cancer were retrospectively reviewed for the period between January 2000 and February 2007 under a study approved by the institutional review board. A multivariate logistic regression analysis of selected prognostic features was done. A nomogram to predict brain metastasis was constructed and validated in a cohort of 128 patients with brain metastasis treated at the Cross Cancer Institute (Edmonton, Alberta, Canada). Results Of 2,136 patients with breast cancer, 362 developed subsequent brain metastasis. Age, grade, negative status of estrogen receptor and human epidermal growth factor receptor 2, number of metastatic sites (one v > one), and short disease-free survival were significantly and independently associated with subsequent brain metastasis. The nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.68 (95% CI, 0.66 to 0.69) in the training set. The validation set showed a good discrimination with an AUC of 0.74 (95% CI, 0.70 to 0.79). The nomogram was well calibrated, with no significant difference between the predicted and the observed probabilities. CONCLUSION We have developed a robust tool that is able to predict subsequent brain metastasis in patients with breast cancer with nonbrain metastatic disease. Selection of an enriched patient population at high risk for brain metastasis will facilitate the design of trials aiming at its prevention.

Breast cancer (BC) is the most frequently occurring cancer in women; early diagnosis and efficient treatments create higher event-free and overall survival rates. However, the mean age at first pregnancy continues to increase worldwide; the question of pregnancy after BC is thus raised more frequently. Chemotherapy may induce premature ovarian failure, depending largely on the woman's age and the drugs used, as well as the dosage and duration of treatment. It is important that fertility preservation strategies are addressed before chemotherapy. Pregnancy after BC may implicate a potentially higher risk of cancer recurrence, but the available literature provides reassuring data. The delay between cancer treatment and pregnancy should be discussed, depending on the initial stage of the disease. The risk of discontinuing tamoxifen prematurely should be carefully evaluated using standardised tools. The pregnancy outcome may as well be impaired by the history of cancer, leading to an increased likelihood of preterm birth and low birth weight rates. Proper follow-up and prevention should be provided based on the knowledge of these complications. Pregnancy after BC should be possible for most young BC patients in the future. This implies a global care program including multi-disciplinary teams is initiated prior to starting adjuvant treatment and particularly chemotherapy. The patient and her partner should be involved in the various steps of the process, after being properly informed., (Copyright 2009 Elsevier Ltd. All rights reserved.)

High risk may be defined as either an absolute risk greater than 20 % or a relative risk greater than 4. Concerning breast and ovarian cancer, high risk patients include carriers of a constitutive deleterious mutation of BRCA1 or BRCA2 genes, patients with a significant family history of breast or ovarian cancer, and patients who have been diagnosed a benign breast lesion with a high risk of degeneration, i.e. atypical hyperplasia. Following up such patients relies on specific strategies. A center including a large panel of physicians involved in the various modalities for patients' management (geneticians, radiologists, gynecologists, plastic surgeons, pathologists, endocrinologists, psychologists, medical oncologists) has been created at Tenon Hospital with this purpose. The collaboration of these different specialists with the referent physician of the patient allows for the definition and the implementation of a patient-centered follow-up continuously updated to take into account the different periods of a woman's life, according to best practices recommendations and the evolving state-of-the art., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Background: The objective of this study was to describe the characteristics and survival outcomes of patients with breast cancer who had ovarian metastases., Methods: Data from 29 women who underwent surgery were reviewed retrospectively (from 1998 to 2007). Patient characteristics, tumor characteristics, and treatment data were collected. Pelvic extent of disease was documented using a system analogous to the International Federation of Gynecology and Obstetrics classification for ovarian cancer. Global survival, disease-free intervals, and the distribution to other metastatic sites over time were studied. Outcomes were compared between the group who underwent macroscopic resection of lesions and the group who did not undergo resection., Results: The data indicated a predominance of premenopausal and hormone receptor-positive status and a greater prevalence of lobular infiltrating carcinoma, bilateral breast cancer, and predisposing genetic factors compared with the global population with breast cancer. Ovarian disease was diagnosed at a median of 5 years after breast cancer. Seventy-five percent of patients were asymptomatic, and advanced-stage pelvic extent or extra-abdominal metastases were observed in 41.5% of patients. The median survival was 3 years, and the median follow-up was 2 years. Survival improved significantly when optimal debulking surgery was performed., Conclusions: Breast cancers may be associated with ovarian metastases. The current results indicated that surgical resection tends to increase survival, which may be long; however, larger series would be needed to confirm other prognostic factors. The high rates of hormone receptor-positive tumors and premenopausal patients led the authors to suggest that the surgical option should consist of at least bilateral oophorectomy, even when the contralateral ovary appears to be normal.

Background: Large-core needle biopsy of the breast (LCNB) and vacuum-assisted breast biopsy (VABB) are widely used as alternatives to open surgical biopsy (OSB) for initial diagnosis of mammographic abnormalities. Between 18% and 80% of cases in which such specimens show atypical lobular hyperplasia (ALH) or atypical ductal hyperplasia (ADH) are found to be malignant at surgery., Design: From 1999 to 2005, 68 women with mammographic abnormalities were sampled by stereotactic VABB and presented atypical epithelial hyperplasia. Immunohistochemical staining with anti-cytokeratin 5/6 and anti-E-cadherin antibodies was performed. All women underwent a lumpectomy. Clinical, radiological or histological factors predictive of the risk of finding malignancy at surgery were sought., Results: VABB initially showed 28 cases of ADH, 32 cases of ALH, one case of flat epithelial atypia, five cases of mixed atypia, and two cases of Lobular Carcinoma In Situ (LCIS). After slide review with immunohistochemical staining, two cases of ADH were reclassified as simple hyperplasia and two cases of ALH were reclassified as mixed atypia. Seven lesions (10.3%) that appeared to be benign on VABB were found to be malignant on OSB (Ductal Carcinoma In Situ (DCIS) in six cases and invasive ductal carcinoma in one case). ADH was the only predictive factor of malignancy on OSB (p=0.04 versus ALH)., Conclusion: ADH diagnosed by vacuum-assisted breast biopsy frequently corresponds to cancer on open surgical biopsy. Surgical excision of all breast lesions containing atypical hyperplasia on percutaneous biopsy can be recommended., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Background: Lymph node status is an important prognostic factor and a criterion for adjuvant therapy in uterine cancers. While detection of micrometastases by ultrastaging techniques is correlated to prognosis in several other cancers, this remains a matter of debate for uterine cancers. The objective of this review on sentinel nodes (SN) in uterine cancers was to determine the contribution of ultrastaging to detect micrometastases., Methods: Review of the English literature on SN procedure in cervical and endometrial cancers and histological techniques including hematoxylin and eosin (H&E) staining, serial sectioning, immunohistochemistry (IHC) and molecular techniques to detect micrometastases., Results: In both cervical and endometrial cancers, H&E and IHC appeared insufficient to detect micrometastases. In cervical cancer, using H&E, serial sectioning and IHC, the rate of macrometastases varied between 7.1% and 36.3% with a mean value of 25.8%. The percentage of women with micrometastases ranged from 0% and 47.4% with a mean value of 28.3%. In endometrial cancer, the rate of macrometastases varied from 0% to 22%. Using H&E, serial sectioning and IHC, the rate of micrometastases varied from 0% to 15% with a mean value of 5.8%. In both cervical and endometrial cancers, data on the contribution of molecular techniques to detect micrometastases are insufficient to clarify their role in SN ultrastaging., Conclusion: In uterine cancers, H&E, serial sectioning and IHC appears the best histological combined technique to detect micrometastases. Although accumulating data have proved the relation between the risk of recurrence and the presence of micrometastases, their clinical implications on indications for adjuvant therapy has to be clarified.

Objective. To study incidence of abnormal hysteroscopic findings according to age. Methods. We retrospectively studied 557 consecutive office hysteroscopies in patients referred for incapacity to conceive lasting at least 1 year or prior to in vitro fertilization. Rates of abnormal findings were reviewed according to age. Results. In 219 cases, hysteroscopy showed an abnormality and more than a third of our population had abnormal findings that could be related to infertility. Rates of abnormal findings ranged from 30% at 30 years to more than 60% after 42 years. Risk of abnormal finding was multiplied by a factor of 1.5 every 5 years. Conclusion. Our data are an additional argument to propose office hysteroscopy as part of first-line exams in infertile woman, regardless of age.

Purpose: Three models have been developed to predict four or more involved axillary lymph nodes (ALNs) in patients with breast cancer with one to three involved sentinel lymph nodes (SLNs). Two scores were developed by Chagpar et al (Louisville scores excluding or including method of detection), and a nomogram was developed by Katz et al. The purpose of our investigation was to compare these models in a prospective, multicenter study., Patients and Methods: Our study involved a cohort of 536 patients having one to three involved SLNs who underwent ALN dissection. We evaluated the area under the receiver operating characteristic curve (AUC), calibration (for the Katz nomogram only), false-negative (FN) rate, and clinical utility of the three models. Results were compared with the optimal logistic regression (OLR) model that was developed from the validation cohort., Results: Among the 536 patients, 57 patients (10.6%) had > or = four involved ALNs. The AUC for the Katz nomogram was 0.84 (95% CI, 0.81 to 0.86). The Louisville score excluding method of detection was 0.75 (95% CI, 0.72 to 0.78). The Louisville score including method of detection was 0.77 (95% CI, 0.74 to 0.79). The FN rates were 2.5% (eight of 321 patients), 1.8% (two of 109 patients), and 0% (zero of 27 patients) for the Katz nomogram and the Louisville scores excluding and including method of detection, respectively. The Katz nomogram was well calibrated. Optimism-corrected bootstrap estimate AUC of the OLR model was 0.86. Using this result as a reasonable target for an external model, the performance of the Katz nomogram was remarkable., Conclusion: We validated the three models for their use in clinical practice. The Katz nomogram outperformed the two other models.

Objective: The aim of our study is to compare the Mammotome and Vacora methods of stereotactic directional vacuum-assisted biopsy in terms of pain and complications., Materials and Methods: From June 2001 to May 2005, 1114 consecutive patients underwent directional stereotactic vacuum-assisted breast biopsy (DVAB) for nonpalpable mammographically detected breast lesions (BI-RADS 3, 4 or 5). Respectively 967 and 147 patients underwent the Mammotome and Vacora procedures. Pain was evaluated with a visual analog scale. Immediate and late complications were recorded., Results: The mean+/-S.D. (range) pain scores in the Mammotome and Vacora groups were 1.7+/-1.8 (0-9) and 2.9+/-2.3 (0-10), respectively (p<0.001). Patient age and operator experience were the main determinants of pain. Immediate complications were significantly more frequent in the Mammotome group (p=0.003), and so were late hematomas (p=0.04). Moderate and severe complications occurred exclusively in the Mammotome group., Conclusion: The Mammotome technique is associated with a higher risk of immediate and late complications, while the Vacora technique is associated with more frequent severe pain. Patient age was the major factor influencing pain. Further prospective studies are needed to clarify factors incriminated in pain or complications after DVAB procedures.

Specialized cell types exploit endosomal trafficking to deliver protein cargoes to cell type-specific lysosome-related organelles (LROs), but how endosomes are specified for this function is not known. In this study, we show that the clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral recycling endosomal subdomains in melanocytes required for cargo delivery to maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of recycling endosomes redistributes to pericentriolar clusters, resulting in sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and consequent inhibition of melanin synthesis and melanosome maturation. Immunocytochemistry, live cell imaging, and electron tomography reveal AP-1- and KIF13A-dependent dynamic close appositions and continuities between peripheral endosomal tubules and melanosomes. Our results reveal that LRO protein sorting is coupled to cell type-specific positioning of endosomes that facilitate endosome-LRO contacts and are required for organelle maturation.

Fetal CD34+ cells enter the maternal circulation during pregnancy and may persist for decades. These cells are usually depicted as hematopoietic stem/progenitor cells. Our objective was to further determine the phenotype of fetal chimeric CD34+ cells in placental maternal blood from the intervillous space (IVS). Human healthy term placentas were analyzed (n=9). All fetuses were male. CD34+ cells were identified in the IVS and further characterized as fetal or maternal using X and Y chromosome fluorescence in situ hybridization. The phenotype of fetal cells was further analyzed using anti-CD117 (c-kit), anti-CD133, anti-CD31, anti-von Willebrand factor (vWF), anti-vimentin, anti-CD45 and anti-cytokeratin (CK) antibodies. We used preeclamptic placentas of male (n=3) and healthy placentas of female fetuses (n=3) as controls. As expected fetal cells were easily identified in the IVS and significantly increased in cases of preeclampsia. Most CD34+ cells in the IVS were of fetal origin (90%) and were not surrounded by CK staining further showing that they were not in fetal trophoblastic villi. Similarly, about 40% of CD31+ and 6% of vimentin+ cells in the IVS were fetal in origin. No CD117+ or CD133+ fetal cells were found in the IVS of examined placentas. Besides, all the CD34+ cells identified in the IVS were co-labeled with vWF or CD31, suggesting their endothelial origin. These results suggest that most CD34+ cells in maternal placental blood at term are fetal in origin from endothelial and not hematopoietic lineages.

Background: Patent blue is a commonly used agent in the detection of sentinel nodes (SN) in solid cancer. Similar to any drug, it is possible to have an allergic reaction during surgery. Anaphylactic reactions to patent blue have been rarely reported especially in cervical cancer., Case: We reported here a rare case of anaphylactic shock due to patent blue in response to injection of patent blue for SN mapping in a woman with cervical cancer. We presented our management of the shock, our diagnostic process of the allergen and the treatment of the cervix cancer after the anaphylactic reaction., Conclusion: Surgeons and anesthetists must be aware of the potential allergic of patent blue during the SN procedure.

Objectives: The use of sentinel node biopsy (SNB) has replaced axillary lymph node dissection (ALND) as the new standard of care in early unifocal breast cancer. In multifocal breast cancer, this procedure remains controversial. The real problem is when a multifocal tumor is discovered during or after the surgery, with a SNB negative which has been already done. Should we do an additional ALND or not?, Patients and Methods: We performed a retrospective study of 43 multifocal breast cancer patients who underwent SNB., Results: The mean histological primary tumor size was 16.8 mm (range, 1-52 mm). The mean number of SN removed was 2.07 (range, 1 to 5). Sixteen (34.1%) of the 43 patients had at least one positive SN. Twenty-seven patients had subsequent axillary dissection. Negative predictive value of SN procedure was 100% (95% confidence interval: 87.1-100%) with a FN rate of 0%. Moreover, not any patient has developed axillary recurrence with a mean follow-up of 20.8 months (1-77)., Discussion and Conclusion: Our data are not powerful enough to validate the SNB in multifocal breast tumor discovered after an initial surgery. However, the FN rate of 0% is encouraging and prospective studies with a systematic ALND can help surgeons to respond to the question.

Purpose: Several models have been developed to predict nonsentinel lymph node (non-SN) status in patients with breast cancer with sentinel lymph node (SN) metastasis. The purpose of our investigation was to compare available models in a prospective, multicenter study., Patients and Methods: In a cohort of 561 positive-SN patients who underwent axillary lymph node dissection, we evaluated the areas under the receiver operating characteristic curves (AUCs), calibration, rates of false negatives (FN), and number of patients in the group at low risk for non-SN calculated from nine models. We also evaluated these parameters in the subgroup of patients with micrometastasis or isolated tumor cells (ITC) in the SN., Results: At least one non-SN was metastatic in 147 patients (26.2%). Only two of nine models had an AUC greater than 0.75. Three models were well calibrated. Two models yielded an FN rate less than 5%. Three models were able to assign more than a third of patients in the low-risk group. Overall, the Memorial Sloan-Kettering Cancer Center nomogram and Tenon score outperform other methods for all patients, including the subgroup of patients with only SN micrometastases or ITC., Conclusion: Our study suggests that all models do not perform equally, especially for the subgroup of patients with only micrometastasis or ITC in the SN. We point out available evaluation methods to assess their performance and provide guidance for clinical practice.

Background: The aims of this retrospective study were to evaluate laparoscopic triage of patients with advanced ovarian cancer towards primary surgery or neoadjuvant chemotherapy, and to analyze outcome according to the treatment., Methods: Between January 2001 and December 2006, 55 patients with stage III - IV ovarian cancer underwent diagnostic laparoscopy. Primary surgery was performed when complete cytoreduction was considered feasible, while the other patients received neoadjuvant chemotherapy (platinum-based combination with taxanes) and interval surgery. All the patients received adjuvant chemotherapy., Results: Patients treated with neoadjuvant chemotherapy (n = 29) had a higher mean body mass index (P = 0.048), higher serum CA 125 levels (P = 0.026), and more metastases (P = 0.045) than patients treated with primary surgery (n = 26). In patients treated with primary surgery, complete cytoreduction and a residual tumour size

Objective: The aim of this study is to evaluate the accuracy and the safety of stereotactic vacuum-assisted breast biopsy with a 10-gauge hand-held portable system., Materials and Methods: Retrospective data review of 288 consecutive breast lesions that underwent stereotactic 10-gauge hand-held portable vacuum-assisted biopsy from October 2004 through March 2006, was performed. The mean number of core specimens and the percentage of complete radiological removal of the target lesion were analysed. ADH and DCIS under-estimation were evaluated, as were the immediate and delayed complications due to the procedure., Results: The mean number of core specimens obtained per procedure was 9 (range 4-24). Complete radiological excision of the target lesion was achieved in 31.6% (91 of 288) with 91% of these lesions smaller than 10mm (mean size 7 mm; range 4-20mm). Under-estimation of ADH and DCIS was 18.2% (2 of 11) and 19.2% (9 of 47), respectively. There was no false negative result within a 3-year follow-up (from 2005 till date). Complications were mild and consisted of immediate bleeding and delayed haematomas., Conclusion: Breast biopsy using 10-gauge vacuum system is an accurate and safe technique for sampling non-palpable breast lesions.

Objective: This study was to determine the long-term outcomes of arterial pelvic embolization for intractable postpartum hemorrhage and particularly its effect on menses, fertility, and outcomes of subsequent pregnancies., Study Design: Fifty-six consecutive patients who underwent emergency pelvic arterial embolization for severe postpartum hemorrhage between April 1995 and July 2005 were included in the study. Patients were contacted to obtain information about menses and fertility after pelvic arterial embolization., Results: Thirty-four women (61.8%) were successfully contacted. One patient had a hysterectomy. Thirty women (91%) reported regular menses. Thirteen women (38.3%) had a total of 20 spontaneous pregnancies. Eight pregnancies ended during the first trimester. The 12 other pregnancies (60%) were all normal and all patients delivered vaginally healthy babies with normal weight for gestational age., Conclusion: The current study suggests that fertility is not adversely affected by arterial pelvic embolization for intractable postpartum hemorrhage and that women can conceive after the procedure with normal pregnancy outcomes.

Sentinel lymph node biopsy (SLNB) has become an alternative to axillary lymph node dissection (ALND) despite the limited recidive long-term results. SLNB can not only reduce ALND morbidity but also provide ultrastadification with serial sectionning and immunohistochemistry analysis which increase the sensitivity of detection of sentinel node (SN) metastasis. Micrometastasis or isolated tumor cells are frequently discovered. However, their diagnostic and pronostic values are still subject to controversy. Most of large randomized trials have determined that double detection (colorimetric and isotopic) improved SN identification rate and decreased false negative rate; and that periareolar injection was equally effective, even superior than peritumoral injection with the major advantage of its simplicity in non palpable tumors. One of the unsolved problems of SLNB is to determine if its indications may be extended to larger tumors, to node sampling before or after neoadjuvant chemotherapy, or after previous lumpectomy or breast surgery, in case of palpable axillary node, and in case of multifocal tumor. Another challenge is to determine if complementary ALND in case of SLND metastasis is necessary, because 40 to 70% of non sentinel nodes (NSN) are tumor-free. Several predictive models (nomograms, scores, partitioning recursive models) have been developed to predict non-SN status in SN-positive patients. These models must be validated in independent cohorts to enable their use in routine.

If the benefit of adjuvant chemotherapy may be determined at the level of a population, to determine the real chemosensitivity of a tumor at the individual level is impossible. The concept of neoadjuvant chemotherapy in patients with localized breast cancer is interesting because it helps to know the chemosensitivity of a tumor "in vivo". It is possible to use a single criterion to predict the effectiveness of targeted therapies. The chemotherapy is not a targeted therapy, and to determine a biological predictive marker of the response has been impossible so far. The development of mathematical models and use of molecular biology may help to predict chemosensitivity. Initial results are promising. The validation of published works is necessary, but applications are numerous.

The MR Breast Imaging Reporting and Data System (BI-RADS) lexicon of the American College of Radiology (ACR) includes a new lesion category defined as non-masslike enhancement. The purpose of this paper is to review the definition of this new entity, illustrate the main imaging features described in the BI-RADS lexicon and to propose a diagnostic approach based on data from the literature in order to achieve diagnosis and optimal patient management.

Pregnancy results in the transfer of stem cells from the fetus to the maternal circulation. These cells are able to migrate and differentiate within various damaged maternal tissues. We recently showed the presence of fetal-derived cells in human breast carcinomas during pregnancy. In this study, we aimed to reproduce these results in a murine model of "pregnancy-associated" breast carcinoma. We bred virgin MMTV-H-Ras transgenic female mice with male mice transgenic for luciferase under the control of the VEGFR2 promoter. Tumors that developed during or following gestation were analyzed and their nuclear grade classified. Fetal cells were detected by Y chromosome Fluorescence in situ hybridization FISH in 9/9 of breast carcinomas but only in 2 liver controls from the same animals. The number of fetal cells was 20 and 4.9 per million maternal cells in these tissues, respectively (p < 0.05). High grade tumors had significantly more fetal cells (p < 0.05). In vivo imaging of the luciferase signal under control of the VEGFR2 promoter as well as von Willebrand staining did not reveal an endothelial phenotype of fetal cells. Sixty two percent of the fetal cells expressed cytokeratins but were not tumoral. In conclusion, fetal cells-expressing cytokeratin-are always present in murine breast carcinomas associated with gestation. Interestingly, high-grade tumors contain more fetal cells.

In breast cancer, nine models have been developed to predict non SN status in patients with SN metastasis. Four models are nomograms: the Memorial Sloan-Kettering Cancer Center nomogram (MSKCC nomogram), the nomogram of Degnim et al. (Mayo nomogram), the nomogram of Pal et al. (Cambridge nomogram), and the nomogram of Kohrt et al. (Stanford nomogram). Three models are scoring systems: the Tenon score, the score from the M.D. Anderson Cancer Center (MDA score), and the score of Saidi et al. Finally, two are recursive partitioning tools developed by Kohrt et al. Before being used in routine, these models have to be validated in independent populations based on discrimination and calibration. However, the main issue is their clinical utility based not only on the low false negative rate but also its potential to discriminate patients with a low risk of non SN involvement. Several institutions have tested the MSKCC nomogram, with AUC ranging from 0.58 to 0.86. It was not validated by four studies which did not recommend its use even in patients with micrometastasis.The external validation of the Tenon score confirmed its relevance with an AUC of 0.82.

Background: Axillary lymph node dissection (ALND) is the standard treatment for patients with sentinel node (SN) metastasis, but most of these patients have negative non-sentinel nodes (non-SN). We have developed a scoring system (the Tenon score) to help identify a subgroup of patients who have a low risk of having non-SN metastases and who may thus forgo ALND. Here we validated the Tenon score in an independent cohort of SN-positive patients., Patients and Methods: We tested the accuracy of the Tenon score for predicting non-SN status in a prospective multicenter study of 226 SN-positive breast cancer patients. We calculated the false-negative rate, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). Receiver operating characteristics (ROC) curves were constructed and the areas under the curve (AUC) were calculated as a measure of discriminatory capacity., Results: At least one non-SN was positive in 63 patients (27.9%). One hundred and twenty (53.1%) of the 226 patients had a Tenon score of 3.5 or less. Among these 120 patients, five had at least one positive non-SN. With a score cut-off of 3.5, the negative predictive value was 95.8% and the false-negative rate was 4.2%. Overall, the Tenon score accurately predicted non-SN status, with an AUC of 0.82 (95% confidence interval, 0.77-0.88)., Conclusion: In this multicenter study of an independent patient population, the Tenon score was accurate and reproducible for predicting non-SN status in breast cancer patients. The simplicity and reliability of the variables on which the Tenon score is based may be an advantage over other scoring systems.

Background: To evaluate the feasibility of a laparoscopic sentinel node (SN) procedure based on combined method in patients with endometrial cancer., Methods: Thirty-three patients (median age 66.1 years) with endometrial cancer of apparent stage I or stage II underwent a laparoscopic SN procedure based on combined radiocolloid and patent blue injected pericervically. After the SN procedure, all the patients underwent laparoscopic bilateral pelvic lymphadenectomy., Results: SNs were identified in only 27 patients (81.8%). The mean number of SNs was 2.5 per patient (range 1-5). Only 18 patients (54.5%) had an identified bilateral SN. The most common site of the SNs was the medial external iliac region (67.6%). Fourteen SNs (19.7%) from 8 patients (24.2%) were found to be metastatic at the final histological assessment. No false-negative SN results were observed., Conclusions: A SN procedure based on a combined detection and laparoscopic approach is feasible in patients with early endometrial cancer. However, because of a low rate of bilateral and global SN detections and problems of injection site using pericervical injection of radiocolloid and blue dye, alternative methods should be explored. Pericervical injections should be avoided.

Objective: The purpose of this study was to investigate the risk of carcinoma in patients with a diagnosis of papilloma of the breast made on ultrasound large core biopsy or stereotactic vacuum-assisted biopsies., Material and Methods: This retrospective database review (2000-2007) included 130 patients with a papilloma diagnosed on preoperative biopsies or excisional surgery specimen. The mean patient age was 52 years (range, 20-80 years). The examinations included mammography and ultrasonography in all 130 patients. The final surgical histology was compared to preoperative biopsy diagnosis, and then factors associated with underestimation of malignancy were evaluated in univariate and multivariate analyses., Results: The preoperative histology was available for 63 patients. Benign papilloma had been identified by ductography in 34 patients and by preoperative biopsy in 48 patients. Mammography showed microcalcifications in 25 cases and nipple discharge was present in 59 patients. Malignancy was found on final histology in 8% of patients with initial diagnosis of benign papilloma. In this study group, age of more than 50 years, presence of nipple discharge and microcalcifications were found to be significantly related to the risk of malignancy (p=0.001, 0.05 and 0.02, respectively)., Conclusion: Since benign papilloma can be associated to malignancy at excisional biopsy, we still recommend surgical excision for papilloma especially when associated to identified risk factors of malignancy.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in tumorigenesis, but little is known of their expression according to mucinous or serous type. This study aimed to evaluate the immunohistochemical expression of MMP-2, -7, -9, MT1-MMP, TIMP-1 and -2 in these tumors. A tissue microarray was set up including 99 serous (25 benign, 27 borderline, 47 malignant) and 79 mucinous (25 benign, 44 borderline, 10 malignant) ovarian tumors. Immunostaining results were scored by using the HSCORE and assessed by univariate, unsupervised hierarchical clustering and multidimensional scaling analyses. Epithelial expression of MMP-2, -7, -9, MT1-MMP, TIMP-2, but not TIMP-1, was higher in serous than mucinous tumors. Stromal expression of MMP-7 was higher in serous tumors. Alterations in MT1-MMP, MMP-7 and -9 were found in malignant serous tumors, while benign and borderline tumors shared similar expressions. By unsupervised hierarchical clustering analysis, mucinous and serous tumors were better differentiated by epithelial than stromal MMP and TIMP immunolabelling. By multidimensional scaling analysis, the expressions of MMPs and TIMPs were scattered in serous tumors and homogeneous for mucinous tumors. In conclusion, our results support the differential expression in MMPs and TIMPs of ovarian tumors according to serous or mucinous histology.

Background: Occult invasive disease could be found at definitive histology in patients initially diagnosed with large ductal carcinoma in situ (DCIS). Sentinel lymph node (SLN) biopsy is a reliable and minimally invasive procedure providing axillary information and avoiding a second operation in this particular group of patients. The aim of our study was to assess the value of SLN biopsy in patients with large DCIS who are at highest risk for being upstaged to invasive carcinoma., Patients and Methods: The study included 195 patients diagnosed with DCIS upon initial core biopsy and undergoing SLN biopsy. Many features were correlated with the presence of unsuspected invasive disease and positive SLN biopsy using univariate and multivariate analyses., Results: Of the 110 patients with pure DCIS, seven patients (6%) had a metastatic lymph node; 31 patients (16%) were found to have invasive disease upon final histology. Univariate analysis of predictors of unsuspected invasive carcinoma showed that patients having a preoperative biopsy that indicated DCIS with microinvasion (DCISM) or large DCIS were at a higher risk of invasive carcinoma after histological examination of the operative specimen. Of the 31 patients who were upstaged to invasive carcinoma at final histology, seven patients (22%) had a positive SLN biopsy. The analysis of predictors of positive SLN in our study shows that diffuse DCIS requiring mastectomy is the main risk factor for SLN metastasis., Conclusion: There are no real predictive factors for invasive disease in patients with an initial diagnosis of DCIS or DCISM. Our study supports the value of SLN biopsy in patients with a preoperative DCISM biopsy or patients with a large pure DCIS biopsy requiring mastectomy.

Background: The relevance of laparoscopy-based score in identifying patients with advanced ovarian cancer for optimal cytoreductive surgery has been evaluated., Methods: 55 patients with stage III-IV ovarian cancer, having undergone both laparoscopy and laparotomy for cytoreductive surgery, were retrospectively analyzed. Seven parameters were assessed: omental cake, peritoneal carcinosis, diaphragmatic carcinosis, mesenteric retraction, bowel infiltration, stomach infiltration, liver metastases. Each parameter was assigned 2 points if present and 0 if not (Fagotti score). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were calculated for each parameter. Receiver Operating Characteristic (ROC) curve analysis was used to predict the surgical outcome., Results: A laparoscopy-based score of >or=8 was associated with suboptimal cytoreduction with sensitivity, specificity, PPV, NPV, and accuracy of 46%, 89%, 89%, 44%, and 60% respectively. ROC curve analysis gave an Area Under the Curve (AUC) of 0.74. A modified score was set up by selecting 4 of the 7 parameters which satisfied the inclusion criteria in our population: diaphragmatic carcinosis, mesenteric retraction, stomach infiltration, liver metastases. Thirteen patients (12%) had a modified score of >or=4 and 42 patients (88%) had a score of <4 with an optimal cytoreduction rate of 0% and 43% respectively (P=0.002). A modified score of >or=4 was associated with suboptimal cytoreduction with sensitivity, specificity, PPV, NPV, and accuracy of 35%, 100%, 100%, 43%, and 56% respectively. ROC curve analysis gave an AUC of 0.68., Conclusion: This simplified laparoscopy-based score was at least as accurate as the Fagotti score to predict resectability.

Objective: The objective of the study was to study factors influencing the use and accuracy of frozen section diagnosis (FSD) of ovarian tumors., Study Design: Surgery was performed in 414 patients with epithelial ovarian tumors between 2001 and 2006. Factors were identified by univariate and multivariate analysis., Results: FSD was requested in 274 patients: 152 benign, 55 borderline, and 67 malignant tumors. Age 50 years or older, tumor size 10 cm or greater, and preoperative evidence of malignancy were associated with FSD request. The sensitivity and specificity of FSD for benign, borderline, and malignant tumors were 97% and 81%, 62% and 96%, and 88% and 99%, respectively. The histologic type (mucinous), tumor size (less than 10 cm), the borderline component (less than 10%), and the pathologist's experience predicted misdiagnosis of borderline tumors. Spread outside the ovary was the only significant predictor of accurate FSD of malignant tumors., Conclusion: FSD is less accurate for borderline than benign and malignant ovarian tumors. The pathologist's experience is a major determinant of diagnostic accuracy.

After a pregnancy, there is a transitory increase in the risk of breast cancer. During the pregnancy, the number of mammary epithelial cells increases massively. This increase seems partly due to the expansion of stem cells and proliferating intermediate cells. This proliferation of epithelial cells is accompanied by angiogenesis and by recruitment of stromal cells, as well as changes of the extracellular matrix. During any pregnancy, there is cell trafficking between mother and foetus. Hematopoietic or mesenchymal foetal stem cells are transferred in maternal circulation and could be used by the tumor as support cells and take part in the tumoral development. The study of the mechanisms of this specific oncogenesis may help to develop chemoprevention strategies.