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Of the 800 pesticides used worldwide, about 650 can affect the functioning of the endocrine system: endocrine disrupting pesticides (EDPs). Dietary or environmental exposure to EDPs is a concern, as their presence is currently demonstrated in most biological fluids. Some EDPs are prohibited, classified as carcinogenic, others are "probable" or "possible" carcinogens when there is limited evidence of their tumor effect. The impact of EDPs on breasts is not well known to date. However, since most EDPs have a long half-life and are lipophilic, breasts, composed mainly of adipose tissue, are a suitable site for their concentration. The objective of our review was to analyze the impact of EDPs related to our environmental exposure on breast cancer risk, through an analysis of recent literature, including epidemiological and biological data. Our review showed a positive association between the presence of EDPs and breast cancer, especially among women farmers or EDPs users but also in the general population. Studies on breast tumors have found a higher concentration of EDPs in estrogen-sensitive tumors. As for mortality, studies are contradictory, but confirm the dangerousness of some EDPs. The different series analyzed have several limitations, such as the low number of EDPs evaluated, small numbers and insufficient follow up. The potentiating effect of different EDPs used concomitantly and the window of exposure to these substances are parameters to be assessed., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Breast background parenchymal enhancement (BPE) is an increasingly studied MRI parameter that reflects the microvasculature of normal breast tissue, which has been shown to change during neoadjuvant chemotherapy (NAC) for breast cancer. We aimed at evaluating the BPE in patients undergoing NAC and its prognostic value to predict recurrence. MRI BPE was visually and quantitatively evaluated before and after NAC in a retrospective cohort of 102 women with unilateral biopsy-proven invasive breast cancer. Pre-therapeutic BPE was not predictive of pathological response or recurrence. Quantitative post-therapeutic BPE was significantly decreased compared to pre-therapeutic value. Post-therapeutic quantitative BPE significantly predicted recurrence (HR = 6.38 (0.71, 12.06), p < 0.05).

Metastasis is a major cause of death in cancer patients. The extracellular matrix molecule tenascin-C is a known promoter of metastasis, however the underlying mechanisms are not well understood. To further analyze the impact of tenascin-C on cancer progression we generated MMTV-NeuNT mice that develop spontaneous mammary tumors, on a tenascin-C knockout background. We also developed a syngeneic orthotopic model in which tumor cells derived from a MMTV-NeuNT tumor. Tumor cells were transfected with control shRNA or with shRNA to knockdown tenascin-C expression and, were grafted into the mammary gland of immune competent, wildtype or tenascin-C knockout mice. We show that stromal-derived tenascin-C increases metastasis by reducing apoptosis and inducing the cellular plasticity of cancer cells located in pulmonary blood vessels invasions (BVI), before extravasation. We characterized BVI as organized structures of tightly packed aggregates of proliferating tumor cells with epithelial characteristics, surrounded by Fsp1+ cells, internally located platelets and, a luminal monolayer of endothelial cells. We found extracellular matrix, in particular, tenascin-C, between the stromal cells and the tumor cell cluster. In mice lacking stromal-derived tenascin-C, the organization of pulmonary BVI was significantly affected, revealing novel functions of host-derived tenascin-C in supporting the integrity of the endothelial cell coat, increasing platelet abundance, tumor cell survival, epithelial plasticity, thereby promoting overall lung metastasis. Many effects of tenascin-C observed in BVI including enhancement of cellular plasticity, survival and migration, could be explained by activation of TGF-β signaling. Finally, in several human cancers, we also observed BVI to be surrounded by an endothelial monolayer and to express tenascin-C. Expression of tenascin-C is specific to BVI and is not observed in lymphatic vascular invasions frequent in breast cancer, which lack an endothelial lining. Given that BVI have prognostic significance for many tumor types, such as shorter cancer patient survival, increased metastasis, vessel occlusion, and organ failure, our data revealing a novel mechanism by which stromal tenascin-C promotes metastasis in human cancer, may have potential for diagnosis and therapy., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The purpose of this study is to evaluate patients' satisfaction after immediate breast reconstruction (IBR) according to the surgical technique., Methods: Included patients had an IBR between 2012 and 2017 and finished their reconstruction since a year. Patients were contacted by phone and their satisfaction was evaluated with the Breast Q questionnaire. According to the surgical technique, patients were divided into 5 groups: DIEP, gracilis, Latissimus Dorsi flap, definitive implant and expander implant. Techniques were grouped into two categories: free flaps and prothesis. Nipple reconstruction techniques were also evaluated: toe pulp grafting, nipple sharing and local flap., Results: Nighty-five patients on the 103 who were eligible accepted to answer the questionnaire. Satisfaction with breasts was stastistically higher in the free flap group (72.6/100) than in the prothesis group (62.7/100) (P<0.01). Physical well-being (chest) was better for the free flap group than for the prothesis group (92.2/100 vs. 85.2/100, P=0.02). Nipple reconstructions with nipple sharing and free flap give a better satisfaction for patients than toe pulp grafting (75.3/100 and 73.5/100 vs. 47.8/100, P<0.01)., Conclusion: IBR with free flap give, in a short time, a statistically higher satisfaction for breast than prothesis. Nipple reconstructions with free flap and nipple sharing give a better satisfaction too., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background uPA and PAI-1 are breast cancer biomarkers that evaluate the benefit of chemotherapy (CT) for HER2-negative, estrogen receptor-positive, low or intermediate grade patients. Our objectives were to observe clinical routine use of uPA/PAI-1 and to build a new therapeutic decision tree integrating uPA/PAI-1. Methods We observed the concordance between CT indications proposed by a canonical decision tree representative of French practices (not including uPA/PAI-1) and actual CT prescriptions decided by a medical board which included uPA/PAI-1. We used a method of machine learning for the analysis of concordant and non-concordant CT prescriptions to generate a novel scheme for CT indications. Results We observed a concordance rate of 71% between indications proposed by the canonical decision tree and actual prescriptions. Discrepancies were due to CT contraindications, high tumor grade and uPA/PAI-1 level. Altogether, uPA/PAI-1 were a decisive factor for the final decision in 17% of cases by avoiding CT prescription in two-thirds of cases and inducing CT in other cases. Remarkably, we noted that in routine practice, elevated uPA/PAI-1 levels seem not to be considered as a sufficient indication for CT for N≤3, Ki 67≤30% tumors, but are considered in association with at least one additional marker such as Ki 67>14%, vascular invasion and ER-H score <150. Conclusions This study highlights that in the routine clinical practice uPA/PAI-1 are never used as the sole indication for CT. Combined with other routinely used biomarkers, uPA/PAI-1 present an added value to orientate the therapeutic choice.

Introduction: This study analyzes postoperative course of different immediate breast reconstruction techniques: deep inferior epigastric perforator flap (DIEP), gracilis, latissimus dorsi flap, expander implants and definitive implants., Methods: All women operated on IBR between 2012 and 2017 in the CHU Strasbourg were included in this retrospective study. The main data collected were healing time, complications, surgical revisions and failure rates. These data were compared between the five IBR techniques to find a significant difference. Two groups were distinguished according to the surgical techniques: free flaps and implants. Data of those groups were compared too., Results: One hundred and ninety three patients have had a breast surgical treatment between 2012 and 2017. Among them, 44 had a bilateral IBR (23%). Early and unserious complications, were less frequent in the implants group than in the free flaps group: 8.6% vs. 33.3% (P<0.01) for unilateral reconstructions and 10.9% vs. 38.9% (P<0.01) for bilateral reconstructions. No surgical failures were found in the free flaps group versus 6.2% for definitive implants and 3.6% for expander implants. Healing time was longer for the free flaps group than for the prothesis group: 5.6 weeks vs. 4.2weeks, (P<0.01)., Conclusion: IBR with free flaps is associated with a higher risk for early and unserious complications as healing disorders, which extend the dressings time. However the failure rate is not higher with free flaps., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Oncoplastic surgery is to treat breast tumors with the help of plastic surgery. Efficiency of breast-conserving treatments (BCT) compared to mastectomies is equivalent. BCT is better accepted but can cause breast deformity, thus further operations. Oncoplastic surgery aims at conserving an acceptable shape to the breast. It ranges from simple remodeling to more complex techniques modifying the width of the breast. According to the quadrant to treat (inner upper, outer upper, inner lower, outer lower, union of quadrants, tumors of the nipple-areola complex, tumors of the inframammary fold), according to the proximity of the tumor to the nipple, and to the size of the breast and tumor, various techniques are displayed. Few touch ups are necessary. Symmetry is managed during the initial operation or after., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Breast reconstruction is an integral part of breast cancer treatment. It must be systematically mentioned when the disease is announced and proposed at an optimal time during cancer management. In case of ductal carcinoma in situ, reconstruction should be proposed at the same time as mastectomy, which generally preserves the skin. The conservation of the nipple-areolar complex should be further evaluated. In the case of invasive breast carcinoma, breast reconstruction is generally proposed at a distance from the oncological time, except for patients requiring neither chemotherapy nor postoperative radiotherapy for whom reconstruction can be immediate. Finally, in the case of prophylactic synchronous contralateral mastectomy, reconstruction should never delay the overall management of breast cancer., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: About 5% of breast cancers are linked to an inherited predisposition, the two most known susceptibility genes being BRCA1 and BRCA2. Recently, new susceptibility genes, including PALB2, have been identified. The risk of breast cancer associated with a deleterious mutation of PALB2, the age of onset of these cancers, their prognosis and associated cancers have so far been the subject of controversy. Our objective was to clarify these different questions from an updated review of the literature., Methods: The analyzed articles were taken from the PUBMED database between January 2008 and December 2015. The keywords used were "breast cancer" and "PALB2"., Results: Women with PALB2 mutations have a higher risk than the general population of developing breast cancer. The relative risk is significant, varying according to the different studies between 3,4 (IC 95%: 2,4-5,9) and 9,47 (IC 95%: 5,72-14,39). The different mutations as well as environmental and geographical factors should be taking into account when interpreting these results. There is currently no proven link between a PALB2 mutation and the occurrence of ovarian or pancreas cancer., Conclusion: PALB2 must be considered as a high-penetrance breast cancer predisposing gene. Women with a PALB2 mutation face an increased risk of triple negative breast cancer and higher risk of death from breast cancer., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: Ovarian tissue cryopreservation is a modern technique of fertility preservation, useful before using ovariotoxic therapies in the treatment of breast cancer. The aim of our literature review was to study ovarian cryopreservation experiences for women with breast cancer, to identify guidelines, constraints and results in the oncological and obstetrical fields., Methods: We searched articles through the PubMed/Medline database, including all French and English references from January 2000 to October 2017. The combination of key words "breast cancer" and "ovarian tissue cryopreservation" allowed us to select 50 articles. We kept 18 publications which matched our subject., Results: Sixteen cases of ovarian transplants among patients treated for breast cancer were published with 14 pregnancies, 11 births and 3 failures. Two cases of breast recurrences were published after ovarian grafting. However, the hindsight in this technique is limited, with a first transplant published in 2004 and only a low number of cases., Perspectives: A national census and comprehensive gathering of data among the patients treated for breast cancer using ovarian tissue cryopreservation would make it possible to better evaluate the occurrence of pregnancies and the carcinological risk of this technique., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Membrane contact sites are cellular structures that mediate interorganelle exchange and communication. The two major tether proteins of the endoplasmic reticulum (ER), VAP-A and VAP-B, interact with proteins from other organelles that possess a small VAP-interacting motif, named FFAT [two phenylalanines (FF) in an acidic track (AT)]. In this study, using an unbiased proteomic approach, we identify a novel ER tether named motile sperm domain-containing protein 2 (MOSPD2). We show that MOSPD2 possesses a Major Sperm Protein (MSP) domain which binds FFAT motifs and consequently allows membrane tethering in vitro MOSPD2 is an ER-anchored protein, and it interacts with several FFAT-containing tether proteins from endosomes, mitochondria, or Golgi. Consequently, MOSPD2 and these organelle-bound proteins mediate the formation of contact sites between the ER and endosomes, mitochondria, or Golgi. Thus, we characterized here MOSPD2, a novel tethering component related to VAP proteins, bridging the ER with a variety of distinct organelles., (© 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Introduction: The objective of our study was to evaluate the risk of cancer after prophylactic nipple-sparing mastectomy (PNSM)., Material and Methods: The PubMed database was consulted using the following key-words: "nipple-sparing mastectomy", "prophylactic", "locoregional recurrence", "oncological risk". Articles published between January 1995 and December 2016 were searched., Results: Out of the 270 articles found, 19 were included. Overall, 15 studies were retrospective, 2 prospective, 2 prospective and retrospective and 3 were multicentric. All told, they involved 3890 patients corresponding to 6786 mastectomies, among which the total number of prophylactic nipple-sparing mastectomies was 3716. Average age of the patients was 44.4years and average follow-up was 38.4months (8-168months); 29.4% of them had a BRCA 1 or 2 mutation; 85 and 15% underwent prosthetic and autologous reconstructions, respectively. Average cancer rates exterior to and within the nipple areolar complex (NAC) were 0.2 and 0.004%, respectively. The overall average rate of histological pre-malignant lesions in the nipple areolar complex was 1.5%. The overall complication rate was 20.5%, and necrosis rates of the nipple areolar complex and the skin were 8.1 and 7.1%, respectively., Conclusion: In prophylactic breast surgery, conservation of the nipple areolar complex does not seem to increase the risk of cancer development. However, short follow-up time and the different methodologies applied in the different studies presently preclude generalization of the technique., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The objective of this review was to determine whether there is an association between hyperthyroidism and the risk of developing a breast cancer from the analysis of data in the literature., Method: The analyzed articles were extracted from the PUBMED database from 2002 to 2017 using the following keywords "hyperthyroidism AND breast cancer" and "thyroid AND breast cancer"., Results: A total of 22 studies were selected, including 8 cohort studies, 12 case-control studies and 2 meta-analyzes. Of these 22 studies, 15 have established a significant epidemiological or biological link between hyperthyroidism and breast cancer. Five of them were particularly interested in Graves' disease, and four demonstrated a positive association between this disease and the onset of breast cancer, especially within three years from the thyropathy diagnosis. These different studies also highlighted the increased risk of breast cancer seen in overweight or postmenopausal women. Contradictions persist over the types of mammary cancers observed and their prognosis., Conclusion: This review reveals that women with hyperthyroidism appear to have a moderately high risk of breast cancer (RR<2). These data are corroborated by solid physiopathological hypotheses. Regardless of the type of thyropathy responsible for hyperthyroidism, care should be taken to ensure that these patients receive a clinical examination of the breasts on an annual basis and mammographic screening every 2 years from the age of 50 years., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Triple negative breast cancers have the highest relapse risk and the least favourable prognosis of all breast cancer subtypes, leading to an escalation of chemotherapy, substantially during recent years. Secretory carcinoma of the breast is a rare triple negative neoplasm, first described in children but more often presenting in adults. We report a case of a 70-years-old woman, initially diagnosed on the biopsy with a triple negative infiltrating Not Otherwise Specified (NOS) carcinoma of the breast, before it was later correctly identified as a secretory carcinoma, notably because of an abundant intra and extracellular secretory material. This new diagnosis, confirmed by fluorescence in-situ hybridization analysis showing ETS variant 6 (ETV6) gene rearrangement, allowed the de-escalation of chemotherapy therapy. Four years later, the patient is free of recurrences., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Aim: Retrospective studies have suggested a protective effect of regional anesthesia against recurrence after cancer surgery. But confirmation of the in vivo antitumor effects is lacking. We examined the in vitro antitumor effects of lidocaine on various breast cancer cell lines and then assessed these properties in vivo at clinically relevant concentrations., Materials and Methods: In vitro experiments: normal breast epithelial cells (NBEC) MCF-10A and three tumor breast epithelial cells (TBEC) lines (MCF-7 luminal A, MDA-MB-231 triple-negative and SKBr3 HER2 positive) were exposed to increasing concentrations of lidocaine. Cell viability, migration and anchorage-independent growth were assessed by MTT, wound healing, and soft-agar growth assays. In vivo experiments: 6-week-old severe combined immunodeficient mice were injected intraperitoneally with MDA-MB-231 cells and were treated with intraperitoneal lidocaine or phosphate-buffered saline. The mice were euthanized when they reached experimental endpoints or sacrificed to determine peritoneal carcinomatosis index and global tumor volumes., Results: Lidocaine reduced the viability of all the cell lines, inhibited migration of TBEC compared to the NBEC, and compromised the anchorage-independent growth of the triple-negative cells. Intraperitoneal lidocaine improved survival of mice with MDA-MB-231 peritoneal carcinomatosis using doses that are consistent with the current clinical settings for analgesia., Conclusion: In agreement with the notion that local anesthesia may be beneficial for cancer therapy, lidocaine has a protective effect against breast cancer cells in experimental studies. However, the beneficial impact of local anesthetics on breast cancer needs to be strengthened by additional preclinical and clinical trials., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we examined clinical, histological, and biological characteristics and mortality of breast cancer in elderly women along with their changes with advancing age., Methods: We reviewed 63 original articles published between 2006 and 2016 concerning women over 70 years with breast cancer., Results: Compared to patients 70-79 years, patients aged 80 and over had larger tumor size with fewer T1 (42.9% vs 57.7%, p < 0.01) and more T2 lesions (43.5% vs 33.0%, p < 0.01). Lymph nodes and distant metastases were more frequent, with more N + (49.5% vs 44.0%, p < 0.01) and more M1 (8.0% vs 5.9%, p < 0.01). Infiltrating mucinous carcinomas were more frequent (4.3% vs 3.7%, p < 0.01). Tumors had lower grades, with more grade 1 (23.2% vs 19.8%, p = 0.01) and fewer grade 3 (21.5% vs 25.5%, p < 0.01), and were more hormone-sensitive: PR was more often expressed (72.6% vs 67.3%, p < 0.01). Lympho-vascular invasion was less frequent in the 80 years and over (22.9% vs 29.7%, p = 0.01). Breast cancer-specific mortality was higher both at 5 years (25.8% vs 17.2%, p < 0.01) and 10 years (32.7% vs 26.6%, p < 0.01)., Conclusion: Clinico-pathological characteristics, increased incidence, and mortality associated with aging can be explained on one hand by biological changes of the breast such as increased estrogen sensitivity, epithelial cell alterations, immune senescence, and tumor microenvironment modifications. However, sociologic factors such as increased life expectancy, under-treatment, late diagnosis, and insufficient individual screening, are also involved.

Background: The aim of this study was the evaluation of breast MRI in determining the size and focality of invasive non-metastatic breast cancers., Methods: The prospective, single-centre study conducted in 2015 compared preoperative MRI with histological analysis of mastectomy., Results: One hundred one mastectomies from 98 patients were extensively analysed. The rates of false-positive and false-negative MRI were 2 and 4% respectively. The sensitivity of breast MRI was 84.7% for the detection of all invasive foci, 69% for single foci and 65.7% for multiple foci. In the evaluation of tumour size, the Spearman rank correlation coefficient r between the sizes obtained by MRI and histology was 0.62. The MRI-based prediction of a complete response to neoadjuvant chemotherapy was 75%., Discussion: MRI exhibits high sensitivity in the detection of invasive breast cancers. False positives were linked to the inflammatory nature of the tumour bed. False negatives were associated with small or low-grade tumours and their retro-areolar location. The size of T1 tumours was overestimated by an average of 7%, but MRI was the most efficient procedure. The sensitivity of MRI for the diagnosis of unifocal tumours was higher than that for multifocal sites. Our study confirmed the positive contribution of preoperative MRI for invasive lobular carcinomas and complete response predictions after neoadjuvant chemotherapy.

Objective: The objective of this review was to assess the level of risk of breast cancer for women exposed to ovulation-inducing therapy (OIT)., Methods: The 25 selected studies were extracted from the PUBMED database from January 2000 until March 2016 with the following key-words: "fertility agents", "infertility treatments", "clomiphene citrate", "buserelin", "ovarian stimulation", "assisted reproductive technology" and "breast cancer". Our meta-analysis was performed using Review Manager software, Cochrane Collaboration, 2014. The results were calculated by type of OIT, as well as globally., Results: The analysis of these published epidemiological studies confirms that exposition to OIT is not a breast cancer risk factor, but the results are contradictory. Two studies have shown a significantly increased risk of breast cancer in a population of infertile women, while two others have found a significant decrease of this risk. The twenty others did not show any impact of IOT over this risk. Our meta-analysis of 20 selected studies has not identified a significant association between exposition to OIT and breast cancer risk (relative risk=0,96; IC 95: (0,81-1,14) for cohort studies and odds ratio=0,94; IC 95% (0,81-1,10) for case-control studies)., Conclusion: Exposition to OIT is not an identified risk factor for breast cancer. A message reassuring about a possible risk of OIT-related breast cancer should be given to these women. Exposition to OIT is therefore not an indication of increased breast surveillance., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Breast fibromatosis is a rare disease characterized by monoclonal fibroblast proliferation. It has no ability to metastasize but has a high local recurrence rate and often infiltrates surrounding tissues. Surgical treatment is the reference, but recently, new targeted therapies have emerged. We report an original case of a patient with breast fibromatosis who received exclusive medical treatment. Our aim was to analyze these treatments based on the clinical and radiological outcome, iatrogenic effects, and pharmacological action., Case Presentation: We report the case of a 19-year-old woman who developed a desmoid-type fibromatosis of the lower inner quadrant of the right breast, measuring 50 × 25 mm (i.e., a volume of 27.4 cm 3 ). Initial surgery was not possible because of potential esthetic and functional prejudice. Thus, she had an exclusive medical treatment including several lines: NSAIDs with tamoxifen and triptorelin, followed by sorafenib, then interferon α2b, and finally sunitinib. With tyrosine-kinase inhibitors (TKIs) (sunitinib), a significant partial response was observed (57% reduction of the maximal tumoral volume). For each treatment, we provided the clinical and radiological outcome in association with known pharmacological action., Conclusions: TKI had been an interesting alternative option to initial surgery, providing at least a partial response and potentially allowing less mutilating surgery. However, no pharmacological mechanism can unequivocally explain TKI efficacy. In general, breast fibromatosis should be treated along with oncologist and interventional radiologists in a trans-disciplinary modality, thus offering an adapted treatment for this particular desmoid-type fibromatosis localization.

The objective of this review was to identify recurrences (ipsilateral, contralateral, metastases and deaths) occurring after controlled ovarian hyperstimulation (COH) or cryopreservation of ovarian tissue (CPTO) for patients treated for a breast cancer., Methods: We performed a bibliographical research through the Pubmed/Medline database, including all the references from January 2006 until September 2016, in French or in English, after exclusion of animal studies. The keywords association "breast neoplasms", "fertility preservation", "reproductive techniques", "ovarian cryopreservation" and "in vitro fertilization" allowed the selection of 852 publications among which only 6 were selected because they included data on recurrence and long term follow up. Four publications involved HSC (3 before breast cancer treatment and 1 after) and 2 concerned CPTO with re-implantation., Results: This analysis has not shown increasing of breast recurrences after HSC and CPTO. However, results were not statistically significant, due to several biases in particular heterogeneousness of the groups of patients., Conclusion: A survey of patients who used fertility preservation or assisted reproductive technologies after breast cancer would be helpful to better estimate their oncological risk., (Copyright © 2017. Published by Elsevier Masson SAS.)

The aim of this literature review was to quantify the incidence and mortality of breast cancer for women treated for a diabetes mellitus and to analyze the complex relationship between these two common diseases., Methods: The articles analyzed were extracted from the PubMed database from 2000 to 2015. A total of 22 case/control studies or cohorts were retained, allowing the realization of a meta-analysis., Results: The incidence of breast cancer for women with diabetes is significantly increased for cohorts (RR=1.32; 95% CI: 1.06 to 1.65) and not significantly for case/control studies (RR=1.46; 95% CI: 0.99 to 2.26). Overall, mortality of women with breast cancer is significantly increased for diabetic patients compared with non-diabetic patients (RR=1.53; 95% CI: 1.23 to 1.90). The links between diabetes and breast cancer are explained by common risk factors (overweight/obesity, qualitative and quantitative dietary errors, physical inactivity), biological changes and the impact of some anti-diabetic treatments or hormonotherapy., Conclusion: Physicians facing a diabetic patient treated for breast cancer have a role in choosing the best anti-diabetic treatment and implementing lifestyle modifications. Diabetic women without breast cancer should participate in organized breast screening programs and have an annual breast clinical examination., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: We explored the clinical utility of human epidermal growth factor receptor-2 extracellular domain (HER2/ECD) in patients treated for an invasive breast cancer with HER2 overexpression., Methods: We prospectively studied HER2/ECD levels in the sera of 334 women included between 2007 and 2014, all treated with trastuzumab. HER2/ECD levels were measured at diagnosis, during treatments, and along the follow-up. We investigated the relationship of HER2/ECD with other clinicopathological parameters at diagnosis, its prognosis value, and its utility during the monitoring of a neoadjuvant treatment and the follow-up., Results: Elevated HER2/ECD at diagnosis correlated positively with parameters associated with tumor aggressiveness. Disease-free survival of non-metastatic patients was significantly shorter in patients with high HER2/ECD at diagnosis (HR = 13.6, 95 % CI 1.6-113.6, P < 0.0001). Progression-free survival of metastatic patients was better for patients with low HER2/ECD (HR = 2.6, 95 % CI 1.2-5.3, P = 0.033). A multivariate analysis revealed that HER2/ECD level at diagnosis was an independent prognosis factor. During neoadjuvant therapy, a significant decrease in HER2/ECD was reported only for the complete histological response group (P = 0.031). During the follow-up, HER2/ECD helped predict relapse, disease progression, and metastases before imaging in 18.6 % cases of the studied cohort., Conclusions: HER2/ECD is a prognosis factor that is valuable in evaluating the neoadjuvant treatment efficiency. HER2/ECD also appears to be a helpful surveillance biomarker for the early diagnosis of relapses and to predict the fate of metastases. This study brings evidences to support the use of HER2/ECD in the management of HER2-positive breast cancer., Competing Interests: The authors have no conflicts of interest to disclose.

Introduction: In France, 126 centers for cancer genetics coordinate genetic testing and high-risk cancer surveillance for individuals and their families with hereditary cancer syndromes. Since 2012, the French National Cancer Institute (INCa) supports 17 projects to promote and manage the monitoring of individuals genetically predisposed to cancer. They were assigned 4 missions by INCa including expertise for difficult cases., Methods: We initiated a national survey to assess how the oncogenetic clinics responded to the 4th mission for women at high risk of developing breast cancers. We sent the survey to all the French oncogeneticists. We aimed at evaluating the modalities and the extent of implementation of the Multidisciplinary team (MDT) meetings regarding the management of women who have genetically higher risks to develop breast cancer., Results: Fourteen people from 12 administrative regions, who represent 10 of the 17 projects, answered the form. Eleven participants reported the submission of medical cases in Oncogenetics MDT meetings (79 %), 5 in senology MDT meetings (36 %), 5 in MDT meetings dedicated to patients at high risk for breast cancer (36 %) and 2 in network meetings (14 %). Some structures discuss medical cases through different MDT meetings., Conclusion: Although MDT meetings are valuable practices to optimize treatment or management options for patients, its settings might be subject to difficulties to federate the appropriate-number of participants as well as cost-effectiveness issues. This survey thus suggests the need of a standardized process of MDT meetings while taking account specificities of oncogenetics., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Unlabelled: Oncoplastic surgery consists a new approach for extending breast conserving surgery possibilities This manuscript aimed to systematically review data on the oncological outcome of oncoplastic breast surgery. Electronic databases were searched with the appropriate search term up to and included April 2013., Inclusion Criteria: full publications including at least 10 patients and providing evidence on at least one of the following outcomes: margin involvement, local recurrence, metastatic disease, death number. Forty studies including 2830 patients, met inclusion criteria; twenty one studies investigated volume displacement techniques; fifteen studies investigated volume replacement techniques; four studies presented data on various oncoplastic techniques. Study quality was low. The majority of studies were observational studies. The length of follow up was relatively short, with only two studies reporting a median duration longer than 60 months. Only seven studies including more than 100 patients. There was great variation in the frequency of margin involvement ranging between 0% and 36% of patients. Local recurrence was observed in 0-10.8% of patients. Distant metastasis was observed in 0-18.9% of patients. In conclusion, long term oncological outcome of oncoplastic surgery for breast cancer is not adequately investigated. Further research efforts should focus on Level I evidence on oncological outcome of oncoplastic surgery., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Screening with breast ultrasound in combination with mammography is needed to investigate a clinical breast mass (Grade B), colored single-pore breast nipple discharge (Grade C), or mastitis (Grade C). The BI-RADS system is recommended for describing and classifying abnormal breast imaging findings. For a breast abscess, a percutaneous biopsy is recommended in the case of a mass or persistent symptoms (Grade C). For mastalgia, when breast imaging is normal, no MRI or breast biopsy is recommended (Grade C). Percutaneous biopsy is recommended for a BI-RADS category 4-5 mass (Grade B). For persistent erythematous nipple or atypical eczema lesions, a nipple biopsy is recommended (Grade C). For distortion and asymmetry, a vacuum core-needle biopsy is recommended due to the risk of underestimation by simple core-needle biopsy (Grade C). For BI-RADS category 4-5 microcalcifications without any ultrasound signal, a minimum 11-G vacuum core-needle biopsy is recommended (Grade B). In the absence of microcalcifications on radiography cores additional samples are recommended (Grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial atypia, radial scar and mucocele with atypia, surgical excision is commonly recommended (Grade C). Expectant management is feasible after multidisciplinary consensus. For these lesions, when excision margins are not clear, no new excision is recommended except for LCIS characterized as pleomorphic or with necrosis (Grade C). For grade 1 phyllodes tumor, surgical resection with clear margins is recommended. For grade 2 phyllodes tumor, 10mm margins are recommended (Grade C). For papillary breast lesions without atypia, complete disappearance of the radiological signal is recommended (Grade C). For papillary breast lesions with atypia, complete surgical excision is recommended (Grade C)., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Trisomy 21 (T21) is the most common chromosomal abnormality and one of the main causes of intellectual disability. The tumor profile of T21 patients is characterized by the low frequency of solid tumors including breast cancer., Methods: The objective of this work was to analyze the literature to find possible clues for the low frequency of breast cancer in T21 persons with a focus on one hand to the various risks and protective factors against breast cancer for women T21, and on the other hand to changes in the expression of different genes located on chromosome 21., Results: T21 women have hormonal and societal risk factors for breast cancer: frequent nulliparity, lack of breastfeeding, physical inactivity and high body mass index. The age of menopause, earlier in T21 women, has a modest protective effect against breast cancer. The low rate of breast tumors in T21 women is probably mainly linked to the reduced life expectancy compared to the general population (risk of death before the age of onset of the majority of breast cancers) and the presence of a third chromosome 21, characterizing the disease. It might lead to the increased expression of a number of genes contributing directly or undirectly to tumor suppression, decreased tumor angiogenesis and increased cell apoptosis. Moreover, changes in the mammary stroma of persons T21 could have an inhibitory role on the development of breast tumors., Conclusion: The low frequency of breast cancers for T21 patients may not only be explained by hormonal and societal factors, but also by genetic mechanisms which could constitute an interesting axis of research in breast cancer., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Unlabelled: The objective of this review was to assess the level of risk of breast cancer of patients consulting for infertility., Methods: Studies of cohorts and case-control were extracted from the Pubmed database from January 2000 until May 2015 through the following keywords: "infertility"; "endometriosis"; "polycystic ovary syndrome"; "breast cancer", "cancer risk". Eleven publications were finally selected after exclusion of publications dealing with infertility after breast cancer. Our meta-analysis, involving 10 of these publications, was performed using Review Manager software, Cochrane Collaboration, 2014. The results were calculated by etiology of infertility, polycystic ovary syndrome (PCOS) and endometriosis, as well as globally., Results: The analysis of these published epidemiological studies confirms that infertility is not a breast cancer risk factor, but the results are contradictory. Three studies have shown a significantly increased risk of breast cancer in a population of infertile women, while 7 others have not found this risk. These contradictions are due to the heterogeneity of the studies, the included populations, the follow-up periods and confounding factors. Our meta-analysis of the selected studies has not identified a significant association between infertility and breast cancer risk (1.05; 95% CI [0.96-1.16]). A subgroup analysis on endometriosis and PCOS showed no significant association either, with an OR of 1.02 (95% CI [0.87-1.19]) and 1.19 (95% CI [0.93-1.51]), respectively., Conclusion: Infertility is not an identified risk factor for breast cancer. A message reassuring about a possible risk of infertility-related breast cancer should be given to these patients. Infertility is therefore not an indication of increased breast surveillance., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the overall survival (OS) of patients with initially inoperable advanced ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma of stages III or IV undergoing neoadjuvant chemotherapy (NAC) followed by cytoreductive surgery, according to the number of cycles performed., Methods: This retrospective study was conducted in three main oncology centres in the east of France, reviewing the charts of all patients who underwent NAC between January 1, 1998 and October 31, 2012. We performed an OS analysis using multivariate Cox regression models adjusted for potential confounders. We also analysed progression-free survival (PFS) as well as chemotherapy- and surgery-related morbidity., Results: Of the 204 patients included, 75 (36.8%) underwent ≤4 NAC cycles and 129 (63.2%) ≥5 NAC cycles. Characteristic data were similar in the two groups. Five-year OS was 35.0 and 25.8%, respectively. This difference was non-significant [HR = 1.06 (0.70-1.59), p = 0.79]. We also found no differences in PFS or morbidity between the two groups., Conclusions: The number of NAC cycles does not seem to play a role in the OS of patients with advanced ovarian cancer. Further evidence and prospective data are needed to assess the value of a high/low number of NAC cycles among these patients., (© 2016 S. Karger AG, Basel.)

Conversely to breast cancer, few data and guidelines are available to explore and manage benign breast disorders. Therefore, the Collège national des gynécologues et obstétriciens français (CNGOF - French College of Gynaecologists and Obstetricians) decided to establish clinical practice guidelines for benign breast tumour (BBT). CNGOF appointed a committee with responsibility for selecting experts, compiling questions and summarizing the recommendations. The summary of valid scientific data for each question analyzed by the experts included a level of evidence, based on the quality of the data available and defined accordingly rating scheme developed by the Haute Autorité de santé (French National Authority for Health)., (Copyright © 2015. Published by Elsevier Masson SAS.)

Objectives: To assess imaging performances for the detection, characterization and biopsy of breast microcalcifications and make recommendations., Materials and Methods: French and English publications were searched using PubMed, Cochrane Library and international learned societies recommendations., Results: Digital mammography (DR [Direct Radiography] and CR [Computed Radiography]) and screen-film mammography demonstrate good performances for the detection and the characterization of breast microcalcifications. Systematic use of the 2013 edition of the BI-RADS lexicon is recommended for description and characterization of microcalcifications. Faced with BI-RADS 4 or 5 microcalcifications, breast ultrasound is recommended but a normal result does not eliminate the diagnosis of cancer and other examination should be performed. Literature review does not allow recommending digital breast tomosynthesis, elastography or MRI to analyze microcalcifications. In case of probably benign microcalcifications (BI-RADS 3), six months, one year and at least two years follow-up are recommended. In case a biopsy is indicated, it is recommended to use a vacuum-assisted macrobiopsy system with 11-gauges needles or bigger. If no calcification is visible on the radiography of the specimen, it is recommended to obtain additional samples., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The development of the mammary imaging (mammography, ultrasound, MRI) enables the discovery of more and more lesions. The BI-RADS lexicon is the reference book for their descriptive analysis. Four elementary images must be individualized: masses and architectural distortion described in 3 imaging techniques, asymmetries and microcalcifications described in mammography. The aim of this work was to review three of these images: mass, architectural distortion and asymmetry, allowing the various actors involved in senology to propose an up-to-date diagnostic and interventional strategy, based on their positive predictive values (PPV) or negative predictive values of cancer and allowing the classification BI-RADS of the lesion. The masses are the most often encountered lesions as well in screening as in diagnosis. Their PPV is superior in diagnosis than in screening and it increases with the age. Their irregular forms, their spiculated outlines and their evolutionary character are the most relevant elements of suspicion. The architectural distortion is the rarest image and always classified suspect BI-RADS 4, except in case of a known scar. The asymmetry is less common; its PPV is low and rises only in case of evolutionary asymmetry., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4-5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4-5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C)., (Copyright © 2015. Published by Elsevier Masson SAS.)

Objective: The aim of this review was to determine the link between night/shift work and breast cancer., Methods: The analysed articles were taken from the PUBMED database between 1996 and 2015. The keywords used were "breast cancer risk", "night work" and "shift work". In total, 25 articles were selected., Results: Night/shift workers are more at risk to develop a breast cancer (relative risk (RR) between 1.09; 95% CI: 1.02-1.20 and 1.48; 95% CI: 1.36-1.61 in the meta-analyses). However, this risk is not found by some cohort and case-control studies. The circadian rhythm disruption, responsible of disorderliness of melatonin secretion, could be one of the mechanisms involved in the increase of that risk. Hormonal status of night/shift workers, their geographic origin, their lifestyle and their vitamin D deficiency appear as other mechanisms potentially responsible for increased risk of cancer in this professional population. Moreover, a dose-effect connection may exist, with an increase of the risk with the number of years of night/shift work., Conclusion: Night/shift work is associated with a moderate increased risk of breast cancer, especially among women who worked over 20 years. Recommendations concerning the breast monitoring in this population could be diffused. The benefit of melatonin supplementation remains to be assessed., (Copyright © 2015. Published by Elsevier SAS.)