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Context: Hormone-dependent gynaecological disorders, such as polycystic ovary syndrome (PCOS) or endometriosis, have been recently discussed as potential risk factors for venous thromboembolism (VTE). Combined hormonal contraceptive (CHC) therapy, which is a well-known risk factor for VTE, is usually used to alleviate symptoms related to these gynaecological disorders. Nevertheless, prevalence of hormone-dependent gynaecological disorders at the time of VTE event and the management of hormonal contraceptives are not well known., Objective: To assess retrospectively the prevalence of hormone-dependent gynaecological disorders in patients with VTE event and the hormonal therapy at the time of VTE event and at the time of inclusion in the present study., Methods: Women aged between 18 to 50-year-old who were hospitalized at Saint-Joseph Hospital (Paris) for a VTE event from January 1st, 2016 to December 31st, 2020 were included in this retrospective observational study., Results: In total, 125 women were included. At the time of VTE event, mean age was 39-years-old (±8) and mean body mass index (BMI) 26kg/m 2 (±8). Pulmonary embolism represented more than two third (68%) of VTE events. Fourteen women (11%) had PCOS and among them, 6 (43%) were using CHC. Eleven women (9%) had endometriosis and among them, 1 (9%) was using CHC. Women with PCOS appeared to be younger at the time of VTE compared to non-PCOS women (mean age 32 years (±6.0) vs. 40 years (±8.0), respectively, P<0.001), whereas women with endometriosis were older with a mean age of 43-year-old (±7.8), which did not differ significantly from women without endometriosis. Among PCOS women, 1 (7%) VTE event was idiopathic, whereas among those with endometriosis, 5 (46%) VTE events were idiopathic. Regarding contraceptive use at the time of inclusion, with a mean delay between VTE event and inclusion of 3 years (±1), 1 woman pursued CHC, 35 (28%) used non-hormonal contraceptive. Seventy-three women (58%) were aware of hormonal contraindications due to VTE event., Conclusion: The present study, including 125 young women with a mean age of 39 years, allowed a description of gynecological pathologies and history of contraceptive use potentially involved in VTE events., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The coronavirus SARS-CoV-2 (COVID-19) outbreak is having a profound impact on the management of patients with cancer. In this review, we comprehensively investigate the various aspects of cancer care during the pandemic, taking advantage of data generated in Asia and Europe at the frontline of the COVID-19 pandemic spread. Cancer wards have been subjected to several modifications to protect patients and healthcare professionals from COVID-19 infection, while attempting to maintain cancer diagnosis, therapy, and research. In this setting, the management of COVID-19 infected patients with cancer is particularly challenging. We also discuss the direct and potential remote impacts of the global pandemic on the mortality of patients with cancer. As such, the indirect impact of the pandemic on the global economy and the potential consequences in terms of cancer mortality are discussed. As the infection is spreading worldwide, we are obtaining more knowledge on the COVID-19 pandemic consequences that are currently impacting and may continue to further challenge cancer care in several countries.

Purpose: . The aim of the study was, through a single institutional analysis of a large population of breast cancer patients, to assess the feasibility of and the tolerance to radiotherapy after the use of magnetic detection method for sentinel lymph node biopsy., Material and Methods: The super paramagnetic iron oxide particles database was collected prospectively and identified 520 cases from October 2013 to December 2016 at our institution. All of them received super paramagnetic iron oxide particles injection 20minutes before the surgical procedure and some of them received also isotope technique. Injection site for super paramagnetic iron oxide particles and isotope was periareolar. Among them, 288 patients received adjuvant radiotherapy. In our study, we evaluated the tolerance of postoperative radiotherapy., Results: The median age of the patients was 64 years. The median follow-up period was 16 months (range: 1-42 months). Double detection of sentinel lymph node was done in the first 30 patients (10.4%). The sentinel lymph node identification rate was 99.7% (287 out of 288). There were 34 axillary lymph node dissections, of which 58.8% were realized straightaway. The total radiation dose was 50Gy EQD2 (range: 28.5-66Gy). Regarding the occurrence of radiodermatitis, 95.8% of patients had grade 0-2 radiodermatitis and 1% had grade 3. During follow-up, 19.4% of patients developed grade 1-2 post-therapeutic fibrosis (of which 92.9% grade 1)., Conclusion: The results of this large-scale study show that the radiotherapy after sentinel lymph node biopsy using super paramagnetic iron oxide particles is feasible, and that no increase of the toxicity was observed., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Modern breast cancer care is a complex multidisciplinary undertaking in which the integrated function of multiple constituent parts is critical, and where changes to one therapeutic component may profoundly influence the delivery and outcomes of another. Oncoplastic and reconstructive breast surgery has evolved in the era of longer survival rates for women with breast cancer and aims to enhance oncological and cosmetic outcomes. However, concurrently there has been an expansion in the indications for post-mastectomy radiation therapy (Abdulkarim et al., 2011; Early Breast Cancer Trialists' Collaborative Group (EBCTCG), 2014; Poortmans et al., 2015; Wang et al., 2011), the recognition of several biologically distinct breast cancer subtypes (Perou et al., 2000; Sørlie et al., 2001, 2003; Cheang et al., 2008, 2009; Sotiriou et al., 2003; Millar et al., 2011; Blows et al., 2010; Schnitt, 2010; Haque et al., 2012; Dai et al., 2015) and the development of recommendations for prophylactic surgery for high-risk women, including BRCA-mutation carriers (James et al., 2006; Domchek et al., 2010). Primary systemic therapy is increasingly utilised yet has varying efficacy depending on tumour biology (Cortazar et al., 2014). In this paper we review the evidence which informs the multidisciplinary team opinion in the era of oncoplastic and reconstructive breast surgery. We aim to describe an optimal multidisciplinary approach which balances competing risks of multimodal therapies to optimise oncological and cosmetic outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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

We developed a new transcutaneous method for breast cancer detection with dogs: 2 dogs were trained to sniff skin secretion samples on compresses that had been worn overnight by women on their breast, and to recognize a breast cancer sample among 4 samples. During the test, the dogs recognized 90.3% of skin secretion breast cancer samples. This proof-of-concept study opens new avenues for the development of a reliable cancer diagnostic tool integrating olfactory abilities of dogs., (© 2018 S. Karger AG, Basel.)

Objectives: To assess the diagnostic performance of ultrasound-guided fine-needle aspiration (USFNA) in nonpalpable breast lesions (NPBLs) in a multidisciplinary setting., Methods: In total, 2,601 NPBLs underwent USFNA by a radiologist-pathologist team. Gold-standard diagnosis was based on surgery, core-needle biopsy, or 1-year imaging follow-up. USFNA's diagnostic performance was analyzed in different clinical and imaging subgroups., Results: USFNA's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 92.6% (95% confidence interval [CI], 90.8%-94.2%), 96.8% (95% CI, 95.8%-97.6%), 94.8% (95% CI, 93.2%-96.1%), and 95.4% (95% CI, 94.3%-96.4%). The best PPV was achieved in Breast-Imaging Reporting and Data System (BI-RADS) categories 4C and 5 and the best NPV in BI-RADS categories 2, 3, and 4A and in patients younger than 50 years. The mitotic count, BI-RADS categories, associated palpable cancer, and age (<50 or ≥50 years) were statistically independent factors ( P  < .05) between USFNA's false-negative and true-positive results., Conclusions: USFNA is a robust diagnostic procedure in NPBLs. Age and the BI-RADS category of the lesion are important factors determining its performance., (© American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: The European Society of Breast Cancer Specialists (EUSOMA) has defined quality indicators for breast cancer (BC). The aim of this study was to describe the preoperative clinical pathway of breast cancer patients and evaluate the determinants of compliance with EUSOMA quality indicators in the Optisoins01 cohort., Methods: Optisoins01 is a prospective, multicentric study. Data from operable BC patients were collected, including results from before surgery to 1 year follow-up. Seven preoperative EUSOMA quality indicators were compared with the clinical pathways Optisoins01., Results: Six hundred and four patients were included. European Society of Breast Cancer Specialists targets were reached for indicator 1 (completeness of clinical and imaging diagnostic work-up), 3 (preoperative definitive diagnosis) and 5 (waiting time). For indicator 8 (multidisciplinary discussion), the minimum standard of 90% of the patients was reached only in general hospitals and comprehensive cancer centres. Having more than 1 medical examination within the centre was associated with an increased waiting time for surgery, whereas it was reduced by having an outpatient breast biopsy. The comprehensive cancer centre type was the only parameter associated with the other quality indicators., Conclusions: European Society of Breast Cancer Specialists quality indicators are a useful tool to evaluate care organisations. This study highlights the need for a standardised and coordinated preoperative clinical pathway.

Background: Avoiding axillary lymph node dissection (ALND) for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB) could decrease morbidity with minimal clinical significance., Purpose: The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN) prediction nomogram for ER+ HER2- breast cancer patients., Methods: We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients' characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results., Results: A 0.3 threshold discriminate the type of sentinel node (SN) metastases: 98.8% of patients with pN0(i+) and 91.6% of patients with pN1(mic) had a MSKCC score under 0.3 (false negative rate = 6.4%). If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients., Conclusion: We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+) or pN1(mic) ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3.

Introduction: Breast cancer surgery is suitable for outpatient practice. Indeed, this is a planned surgery with short operative time. Objective was to evaluate the recognized success indicators in day surgery: rate of conversion into conventional hospitalization, rate of complications and re-hospitalizations the month following surgery., Methods: Consecutive cases of breast cancer patients operated in day surgery were prospectively entered into the Day Surgery database between 25 November 2012 and 31 December 2013. Patient characteristics and tumor pathology, preoperative procedures and type of surgery were collected. Statistical analysis was performed., Results: Three hundred and ninety-six consecutive patients were included. The mean age was 54 years [25-84], we performed 382 conservative breast surgery (98.2%), 238 sentinel node (60.1%) and 40 axillary lymphadenectomy (10.1%). Thirty-nine scheduled for outpatient surgery were hospitalized in conventional surgery being a conversion rate of 9.8%, 95% CI [6.9-12.7] with 24 patients because of a drainage (61.5%). We have observed 15 complications in the month after the surgery (3.7%, 95% CI [1.8-5.6]), and 5 rehospitalization in the month following surgery (1.2%, IC 95% [0.1-2.3])., Conclusion: Postoperative complication and readmissions are very low (<5%) after breast ambulatory surgery. This confirms its feasibility and safety in a breast cancer center. Adaptating anaesthetic methods to ambulatory care and preparing patient going home with an axillary drain are necessary to reduce rate of conversion to hospitalisation., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Treatment strategies for locally advanced breast cancer in elderly patients too frail to receive neoadjuvant chemotherapy and the introduction of new classes of drugs in the early 2000s have led to the consideration of endocrine therapy as a neoadjuvant treatment for younger hormone receptor (HR)-positive, postmenopausal patients not eligible for primary breast-conserving surgery (BCS)., Methods: This was a multicenter, phase 2, randomized trial designed to evaluate as its primary objective the clinical response rate after up to 6 months of neoadjuvant endocrine therapy (NET) alone in HR-positive/human epidermal growth factor receptor 2 (HER2)-negative patients with 1 mg of anastrozole (arm A) or 500 mg of fulvestrant (arm B). Secondary objectives included the BCS rate, tumor response assessment (breast ultrasound and magnetic resonance imaging), pathological response (Sataloff classification), safety profile, relapse-free survival (RFS), and predictive markers of responses and outcomes., Results: From October 2007 to April 2011, 116 women (mean age, 71.6 years) with operable infiltrating breast adenocarcinoma (T2-T4, N0-N3, M0) were randomized to receive anastrozole or fulvestrant. The clinical response rates at 6 months were 52.6% (95% confidence interval [CI], 41%-64%) in arm A and 36.8% (95% CI, 25%-49%) in arm B. BCS was performed for 57.6% of arm A patients and 50% of arm B patients. The RFS rates at 3 years were 94.9% in arm A and 91.2% in arm B. The Preoperative Endocrine Prognostic Index status was significantly predictive of RFS. Both treatments were well tolerated., Conclusions: Both drugs are effective and well tolerated as NET in postmenopausal women with HR-positive/HER2-negative breast cancer. NET could be considered a treatment option in this subpopulation. Cancer 2016;122:3032-3040. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Tumors of trophoblast implantation site TTSI are rare gestational tumors. This case highlights the diagnostic difficulties and treatment of tumors of trophoblastic implantation site early. Patient of 28 years with no medical history, G1P1 who gave birth 11 months ago presented bleeding with an HCG level of 73IU that led to the diagnosis of early miscarriage. Treatment of miscarriage by hysteroscopy and curettage is complicated leading to the realization of an abdominopelvic CT and pelvic ultrasound that show an atypical uterine vascularity and an intracavitary heterogeneous mass. The pelvic MRI performed evokes a TTSI stage I. A hysterectomy with bilateral salpingectomy and ovarian conservation is achieved. Despite the standard treatment with surgery the HCG levels do not normalize before seven months after surgery. This indicates an adjuvant chemotherapy, the patient refuses. The presented case illustrates the diagnostic difficulties of the disease. He noted the importance of the second reading network proposed by the specialized center in Lyon. It also raises the question of adjuvant chemotherapy in some cases of early stage TTSI. The challenge is to define cases requiring adjuvant therapy. Predictors of chemotherapy in early stages could be tumor size, degree of infiltration of the myometrium and mutation p53. Amenorrhea, bleeding associated with uterine atypical vascularization, and atypical development of HCG<1000IU and/or unusual complications of treatment of miscarriage should evoke a tumor site trophoblastic implantation. Hysterectomy is the first treatment in early stages. Tumor size, degree of infiltration of the myometrium and mutation p53 are predictors to assess in multicentre studies to define the indications of postoperative chemotherapy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Introduction: To assess the patient's satisfaction in a day-surgery unit in oncology for a surgical diagnosis or therapeutic act., Methods: Between October 2013 and February 2014, we conducted a satisfaction survey from the validated questionnaire COPS-D. This questionnaire analyse the patient's stages in the care system, from the preoperative consultation to the return home: 9 stages with 23 items rated 1 (bad) to 5 (excellent). It was sent by postmail 3 weeks after their hospitalization., Results: Four hundred and sixty-seven questionnaires were mailed, with a response's rate to 38% (172/467). Participant's characteristics: 88% are women, 45% are full time workers, 54% of senology. Two-third of the assessments were rated 4 or 5. Five percent were rated 1 or 2. The patient's exit is the least preferred step. The operating room's assessment is the most preferred by patients. Sixty-one percent of participants have written a free comment, 31% are positives, 36% are negatives, and 32% are mixed. The wait was the negative recurrent comment (21%)., Discussion: Most participants are very satisfied. Improving the wait before the operation and output is already underway. Studies are now needed to assess the care's safety and the economic aspect of day-surgery., (Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Laparoscopy allows hysterectomies after chemoradiation to be performed without opening the abdominal wall. We measured the costs and quality of life for locally advanced cervical cancer patients operated on via laparoscopy compared to laparotomy., Study Design: We conducted an observational prospective multicenter study on locally advanced cervical cancer patients undergoing an extrafascial hysterectomy after concurrent chemoradiotherapy (CRT). We assessed the costs from the medical visit before surgery up to the first month after surgery from the providers' perspective and measured the quality of life using the EORTC QLQ-C30 and QLQ-CX24 up to six months., Results: Sixty two patients (39 laparoscopy and 23 laparotomy) from December 2008 to November 2011 were included. There was no difference in operative time, or intraoperative and post-operative complication rates between the two groups. Intraoperative transfusion and abdominal drain were significantly lower in the laparoscopy group (respectively, p = 0.04 and p < 0.01), as well as the duration of hospital stay (7.3 d vs. 5.7 d, p < 0.001). All patients who underwent laparoscopic hysterectomy were discharged to home, whereas 4 laparotomy patients used convalescence homes (p = 0.01). Mean costs at one month were €10,991 for laparotomy and €11,267 for laparoscopy (p = 0.76). Sexual activity is better for the laparoscopy group at six months (p = 0.01)., Conclusion: Laparoscopy for an extrafascial hysterectomy after CRT in locally advanced cervical cancer patients brought better quality of life with similar costs compared to laparotomy, and should therefore be the first choice for surgeons., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The current retrospective study was intended to obtain up-to-date and comprehensive data on surgical practice for breast cancer throughout France, including neoadjuvant chemotherapy (NAC) and the more recent surgical techniques of oncoplastic surgery (OPS)., Methods: In June 2011, e-mail surveys were sent to 33 nationally renowned breast cancer surgeons from French public or private hospitals. The questionnaire focused on all the new cases of breast cancer treated in 2010. It included questions regarding surgical practices, with special emphases on NAC and OPS and other surgical characteristics., Results: The overall response rate for the survey was 72.7 %. The total number of breast cancer cases from the survey was 13,762, which constitutes 26.2 % of the total incidence in 2010. Breast-conserving surgery (BCS) was performed for 71.0 % of the patients, and the results were similar throughout the types of practices. Of these patients, 13.9 % received OPS, either upfront or after NAC. Mastectomy was performed for 29.0 % of the patients, which is consistent with French official numbers. Among all patients, 16.3 % underwent surgery after NAC., Conclusion: To the authors' knowledge, there are no publications of national figures on NAC or OPS rates to date. They are convinced that this study offers real-life surgical care information on a large population and covers France's breast cancer surgical landscape. Mastectomy rates in France remain stable and consistent with those in other European countries. However, additional large-scale retrospective studies are required to confirm these figures and further explore NAC and OPS rates as well as surgical practice characteristics.

Background: A care pathway is defined as patient-focused global care that addresses temporal (effective and coordinated management throughout the illness) and spatial issues (treatment is provided near the health territory in or around the patient's home). Heterogeneity of the care pathways in breast cancer (BC) is presumed but not well evaluated. The OPTISOINS01 study aims to assess every aspect of the care pathway for early BC patients using a temporal and spatial scope., Methods/design: An observational, prospective, multicenter study in a regional health territory (Ile-de-France, France) in different types of structures: university or local hospitals and comprehensive cancer centers. We will include and follow during 1 year 1,000 patients. The study consists of 3 work-packages: - Cost of pathway The aim of this WP is to calculate the overall costs of the early BC pathway at 1 year from different perspectives (society, health insurance and patient) using a cost-of-illness analysis. Using a bottom-up method, we will assess direct costs, including medical direct costs and nonmedical direct costs (transportation, home modifications, home care services, and social services), and indirect costs (loss of production). - Patient satisfaction and work reintegration Three questionnaires will assess the patients' satisfaction and possible return to work: the occupational questionnaire for employed women; the questionnaire on the need for supportive care, SCNS-SF34 ('breast cancer' module, SCNS-BR8); and the OUTPASSAT-35 questionnaire. - Quality, coordination and access to innovation Quality will be evaluated based on visits and treatment within a set period, whether the setting offers a multidisciplinary consultative framework, the management by nurse coordinators, the use of a personalized care plan, the provision of information via documents about treatments and the provision of supportive care. The coordination between structures and caregivers will be evaluated at several levels. Day surgery, home hospitalization and one-stop breast clinic visits will be recorded to assess the patient's access to innovation., Discussion: The assessment of care pathways encourages the implementation of new payment models. Our approach could help health care professionals and policymakers to establish other cost-of-illness studies and plan the allocation of resources on a patient basis rather than a visit basis.

Objective: To compare the clinic-pathologic variables and the prognosis of endometrial cancer in patients with and without previous breast cancer, with and without Tamoxifen., Methods: We analyzed patients treated for an endometrial carcinoma from 1994 to 2004: patients without breast cancer (group 1), patients with a previous breast cancer without tamoxifen (group 2) and patients treated for breast cancer with tamoxifen (group 3). Survival rates were calculated according to Kaplan-Meier method and compared using a Log rank test, multivariate analysis was performed with a Cox regression model., Results: 363 patients were analyzed. 80 patients had a previous history of breast cancer (43 received tamoxifen). Although it was not statistically significant, more carcinosarcomas were observed in patients in group 3 than patients in groups 1 and 2 (11.7% versus 4.2% and 5.4% respectively, p = 0.17).) Median follow-up was 87 months [2-185]. 5-year overall survival rate was respectively in groups 1, 2 and 3: 82%, 73.2%, and 61% (p = 0.0006). 5-year local relapse-free survival rate was respectively: 95.9%, 93.1% and 82.5% (p = 0.02). In multivariate analysis, factors affecting overall survival rate were: age ≥65 ans (HR 3.62, p < 0.0001), FIGO stage (HR 3.33 p < 0.0001 for locally advanced stage versus early stage, HR 8.87 p = 0.03 for distant extension versus early stage), and group 3 (HR 2.83 p < 0.001 versus group 1)., Conclusion: Patients with endometrial cancer previously treated for breast cancer show a worse prognostic, particularly if they reveived tamoxifen., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The first descriptions of ulcerated breast cancer date back to ancient Egypt. From the Greek and Roman periods to the Renaissance, fungating wounds were described, excised, cauterized and necrotized using various techniques and unguents. The foundations of some of the therapeutic strategies we still use today were developed.Today the management of inoperable malignant wounds that are not amenable to anti-cancer treatment remains complex and the symptoms are difficult to control.

Background: The aims of the study were to investigate the factors associated with not having breast reconstruction following mastectomy and to assess patient satisfaction with information on reconstruction., Patients and Methods: We analysed a historical cohort of 1937 consecutive patients who underwent mastectomy at Institut Curie between January 2004 and February 2007. Their sociodemographic and clinicobiological characteristics were recorded in a prospective database. A questionnaire was sent to 10% of nonreconstructed patients., Results: The proportion of patients with invasive cancer was 82.7%. The rate of nonreconstruction in patients with in situ and invasive cancer was 34.6% and 74.9%, respectively. On multivariate analysis, only employment outside the home was associated with reconstruction in patients with in situ cancer (p < 0.001). In patients with invasive cancer, employment status (p < 0.001) and smoking (p = 0.045) were associated with reconstruction, while age > 50, ASA score >1, radiotherapy (p < 0.0001) and metastatic status (p = 0.018) were associated with nonreconstruction. For 80% of questionnaire responders, nonreconstruction was a personal choice, mainly for the following reasons: refusal of further surgery, acceptance of body asymmetry, risk of complications and advanced age. Information on reconstruction was entirely unsatisfactory or inadequate for 62% of patients., Conclusion: Better understanding the factors that influence decision of nonreconstruction can help us adapt the information to serve the patient's personal needs.

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

Introduction. In non-metastatic breast cancer patients, the REMAGUS02 neoadjuvant study was the first to report a significant impact of circulating tumor cells (CTCs) detection by the CellSearch system on the distant metastasis-free survival (DMFS) and overall survival (OS) endpoints. However, these results were only reported after a short follow-up. Here, we present the updated data, with a longer follow-up. Material and Methods. CTC count was performed before and after neoadjuvant chemotherapy in 118 patients and correlated to survival. Results. CTC count results were available before and/or after neoadjuvant chemotherapy in 115 patients. After a median follow-up of 70 months, detection of ≥1 CTC/7.5 mL before chemotherapy (N = 95) was significantly associated with DMFS (P = 0.04) and OS (P = 0.03), whereas postchemotherapy CTC detection (N = 85) had no significant impact. In multivariable analysis, prechemotherapy CTC and triple negative phenotype were the two independent prognostic factors for survival. We observed that the CTC impact is most significant during the first three years of follow-up. Discussion. We confirm that the detection of CTC is independently associated with a significantly worse outcome, but mainly during the first 3-4 years of follow-up. No prognostic impact is seen in patients who are still relapse-free at this moment.

Background: Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1-pT2, pN0) breast cancer patients., Methods: 456 patients treated in 1995-1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed., Results: All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5-191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (>20%) Ki67 rate [HR = 3 (1.8-4.8), p<10e-06] and HG3 [HR = 4.4 (2.2-8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5-4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01-4.8), p = 0.04]., Conclusions: We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1-pT2, pN0, breast cancers.

Background: The molecular subtypes of breast cancer have different axillary status. A nomogram including the interaction covariate between estrogen receptor (ER) and HER2 has been recently published (Reyal et al. PLOS One, May 2011) and allows to identify the patients with a high risk of positive sentinel lymph node (SLN). The purpose of our study was to validate this model on an independent population., Methods: We studied 755 consecutive patients treated at Institut Curie for operable breast cancer with sentinel node biopsies in 2009. The multivariate model, including age, tumor size, lymphovascular invasion and interaction covariate between ER and HER2 status, was used to calculate the theoretical risk of positive sentinel lymph node (SLN) for all patients. The performance of the model on our population was then evaluated in terms of discrimination (area under the curve AUC) and of calibration (Hosmer-Lemeshow HL test)., Results: our population was significantly different from the training population for the following variables: median tumor size in mm, lymphovascular invasion, positive ER and age. The nomogram showed similar results in our population than in the training population in terms of discrimination (AUC=0.72 [0.68-0.76] versus 0.73 [0.7-0.75] and calibration (HL p=0.4 versus p=0.35)., Conclusions: Despite significant differences between the two populations concerning variables which are part of the nomogram, the model was validated in our population. This nomogram is robust over time to predict the likelihood of positive SLN according to molecular subtypes defined by surrogate markers ER and HER2 determined by immunohistochemistry in clinical practice., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Description of the various modalities of breast and ovarian cancer risk management, patient choices and their outcome in a single-center cohort of 158 unaffected women carrying a BRCA1 or BRCA2 germline mutation. Between 1998 and 2009, 158 unaffected women carrying a BRCA1 or BRCA2 gene mutation were prospectively followed. The following variables were studied: general and gynecological characteristics, data concerning any prophylactic procedures, and data concerning the outcome of these patients. Median age at inclusion was 37 years and median follow-up was 54 months. Among the 156 women who received systematic information about prophylactic mastectomy, 5.3 % decided to undergo surgery within 36 months after disclosure of genetic results. Prophylactic salpingo-oophorectomy was performed in 68 women. Among women in whom follow-up started between the ages of 40 and 50 years, prophylactic salpingo-oophorectomy was performed, within 24 months after start of follow-up, in 83.7 and 52 % of women with BRCA1 and BRCA2 mutations, respectively. Twenty four women developed breast cancer. Ovarian cancer was detected during prophylactic salpingo-oophorectomy in two women (2.9 %). In this cohort of French women carrying BRCA1/2 mutations, prophylactic mastectomy was a rarely used option. However, good compliance with prophylactic salpingo-oophorectomy was observed. This study confirms the high breast cancer risk in these women.

Objectives: Breast cancer treatment relies on 3 major phenotypical subtypes, including the triple-negative (TN), HER2-positive, and hormone receptor-positive (estrogen receptor/progesterone receptor) ones. We retrospectively determined the clinical and pathologic response rates to intensified taxane-free neoadjuvant chemotherapy according to these phenotypical classes in a series of patients with highly proliferative operable breast cancer, and examined the patterns of recurrence., Methods: Patients with early breast cancer with highly proliferative (S-phase fraction >4%) operable tumors of >3 cm received 4 cycles of intensified neoadjuvant chemotherapy with high-dose cyclophosphamide (doxorubicin 70 mg/m d1, cyclophosphamide 700 mg/m d1/d8, and 5 FU 700 mg/m d1-d5) every 3 weeks., Results: Fifty-five patients were included in the analysis. Patients with TN phenotype experienced a high pathologic complete response (pCR) rate to intensified chemotherapy in comparison with patients with HER2-positive and estrogen receptor/progesterone receptor tumors (47%, 0%, and 12%, respectively). Forty percent of patients with TN breast cancer recurred after a median follow-up of nearly 11 years, but only 22% of those achieving a pCR., Conclusions: A high pCR rate to short intensified neoadjuvant chemotherapy with high-dose cyclophosphamide was achieved in patients with operable highly proliferative TN breast cancer, and pCR was associated with a low rate of recurrence.

Background: The clinical management of lobular carcinoma in situ lesions remains challenging. Our aim was to evaluate the risk of relapse for lobular carcinoma in situ (LCIS) patients, diagnosed on mammography performed for microcalcifications and according to proliferation assessed by Ki67 staining., Methods: A series of 47 patient's files with LCIS and followed in our institution were retrospectively selected. All patients underwent lumpectomy without radiation therapy. The expression of E-cadherin, estrogen receptor (ER), progesterone receptor (PR), EGFR and Ki67 were determined. Four different classes were then defined with the following criteria: ER+ and Ki67 ≤ 10%; ER+, Ki67 >10%; ER-; ER-PR- and EGFR+., Results: Patient's mean age was 51.3 yrs. The majority of the lesions were classical LCIS (97%). All cases were E-cadherin either negative (71%) or weak and incomplete (29%). Among the 44 evaluable cases, 34 cases were ER or PR positive with KI67 ≤ 10% (79%), 9 cases ER positive with KI67 > 10% (21%), 1 case was ER and PR negative and expressed EGFR. At five years, all patients were alive, 1/34 ER positive and Ki67 low experienced a relapse contrasting with 3 out of 9 ER positive and Ki67 high (3 invasive carcinomas including 2 ductal and 1 lobular) (p = 0.0054)., Conclusion: In this retrospective study, we observed a higher risk of relapse associated with a high proliferative activity of classical LCIS. If confirmed in larger series, this observation suggests that radiation therapy or hormonotherapy could be discussed for patients with Ki67 high classical LCIS in order to decrease their risk of relapse., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Resistance to endocrine therapy is a major complication of luminal breast cancer and studies of the biological features of hormonal resistance are limited by the lack of adequate preclinical models. The aim of this study is to establish and characterize a panel of primary human luminal breast carcinoma xenografts, and to evaluate their response to endocrine therapies. Four hundred and twenty-three tumor fragments obtained directly from patients have been grafted in the interscapular fatpad of Swiss nude mice. After stable engraftment with estradiol supplementation, xenografted tumors have been validated by conventional pathology and immunohistochemistry examination, and additional molecular studies. In vivo tumor growth and response to different endocrine treatments were evaluated. We have engrafted 423 tumors including 314 ER+ tumors, and 8 new luminal breast cancer xenografts have been obtained (2.5%). Tumor take was much lower for luminal tumors than for non-luminal tumors (2.5 vs. 24.7%, P < 0.0001), and was associated with two independent criteria, i.e., ER status (P < 0.0001) and a high grade tumor (P = 0.05). Histological and immunohistochemical analyses performed on patient's tumors and xenografts showed striking similarities in the tumor morphology as well as in the expression level of ER, PR, and HER2. Response to hormone therapy, evaluated in 6 luminal models, showed different sensitivities, thus exhibiting heterogeneity similar to what is observed in the clinic. We have established a panel of primary human luminal breast cancer xenografts, recapitulating the biological and clinical behaviors of patient tumors, and therefore suitable for further preclinical experiments.

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

Introduction: In most cases of cervical cancers, HPV DNA is integrated into the genome of carcinoma cells. This mutational insertion constitutes a highly specific molecular marker of tumor DNA for every patient. Circulating tumor DNA (ctDNA) is an emerging marker of tumor dynamics which detection requires specific molecular motif. To determine whether the sequence of the cell-viral junction could be used in clinical practice as a specific marker of ctDNA, we analyzed a series of cervical cancer patient serums., Methods and Findings: Serum specimens of 16 patients diagnosed with HPV16/18-associated cervical cancer, and for which the viral integration locus had been previously localized, were analyzed. Sequential serum specimens, taken at different times during the course of the disease, were also available for two of these cases. ctDNA was found in 11 out of 13 patients with tumor size greater than 20 mm at diagnosis, and analysis of sequential serum specimens showed that ctDNA concentration in patients serum was related to tumor dynamics., Conclusions: We report that HPV mutational insertion constitutes a highly specific molecular marker of ctDNA in HPV-associated tumor patients. Using this original approach, ctDNA was detected in most cervical cancer patients over stage I and ctDNA concentration was found to reflect tumor burden. In addition to its potential prognostic and predictive value, HPV mutation insertion is likely to constitute a new molecular surrogate of minimal residual disease and of subclinical relapse in HPV-associated tumor. This is of major importance in the perspective of specific anti-HPV therapy.

Objective: To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma., Methods: 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates., Results: 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively)., Conclusions: Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery., (Copyright © 2011 Elsevier Inc. All rights reserved.)