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

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

Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.

BACKGROUND: The aim of this study was to compare clinical and pathological outcomes after neoadjuvant chemotherapy between oestrogen receptor (ER)-positive invasive pure lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). METHODS: This analysis included 1895 patients (n=177 ILC; n=1718 IDC), with stage I-III breast cancer, who received neoadjuvant chemotherapy. Clinical and pathological response rates, the frequency of positive surgical margins and rate of breast-conserving surgery were compared. RESULTS: There was a trend for fewer good clinical responses in ILC compared with IDC. Tumour downstaging was significantly less frequent in ILC. Positive or close surgical resection margins were more frequent in ILC, and breast-conserving surgery was less common (P<0.001). These outcome differences remained significant in multivariate analysis, including tumour size, nodal status, age, grade and type of chemotherapy. Invasive pure lobular carcinoma was also associated with a significantly lower pathological complete response (pCR) rate in univariate analysis, but this was no longer significant after adjusting for tumour size and grade. CONCLUSION: Neoadjuvant chemotherapy results in lower rates of clinical benefit, including less downstaging, more positive margins and fewer breast-conserving surgeries in ER-positive ILC compared with ER-positive IDC. Pathological complete responses are rare in both groups, but do not significantly differ after adjusting for other variables.

International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer.

We examined whether baseline Ki67 expression in estrogen receptor-positive (ER+) primary breast cancer correlates with clinical benefit and time to progression on first-line endocrine therapy and survival in metastatic disease. Ki67 values and outcome information were retrieved from a prospectively maintained clinical database and validated against the medical records; 241 patients with metastatic breast cancer were included--who had ER+ primary cancer with known Ki67 expression level--and received first-line endocrine therapy for metastatic disease. Patients were assigned to low (<10 %), intermediate (10-25 %), or high (>25 %) Ki67 expression groups. Kaplan-Meier survival curves were plotted and multivariate analysis was performed to assess association between clinical and immunohistochemical variables and outcome. The clinical benefit rates were 81, 65, and 55 % in the low (n = 32), intermediate (n = 103), and high (n = 106) Ki67 expression groups (P = 0.001). The median times to progression on first-line endocrine therapy were 20.3 (95 % CI, 17.5-38.5), 10.8 (95 % CI, 8.9-18.8), and 8 (95 % CI, 6.1-11.1) months, respectively (P = 0.0002). The median survival times after diagnosis of metastatic disease were also longer for the low/intermediate compared to the high Ki67 group, 52 versus 30 months (P < 0.0001). In multivariate analysis, high Ki67 expression in the primary tumor remained an independent adverse prognostic factor in metastatic disease (P = 0.001). Low Ki67 expression in the primary tumor is associated with higher clinical benefit and longer time to progression on first-line endocrine therapy and longer survival after metastatic recurrence.

Factors Involved in Delaying Initiation of Adjuvant Chemotherapy After Breast Cancer Surgery.

BACKGROUND: Delays in initiating adjuvant chemotherapy after breast cancer surgery seems to have an impact on patients' risk of relapse and their survival rate. The aim of this retrospective study was to identify factors delaying initiation of adjuvant chemotherapy after breast surgery. MATERIAL AND METHODS: All patients undergoing surgical treatment for mammary cancer between June 2014 and June 2015 and receiving adjuvant chemotherapy were selected retrospectively. RESULTS: In multivariate analysis, 3 factors significantly delay initiation of adjuvant chemotherapy: a secondary procedure (odds ratio [OR], 6.67; P = .00012), inclusion in a therapeutic trial (OR, 8.46; P = .0013), and a positive HER2 status (OR, 3.02; P = .063 [statistically significant]). DISCUSSION: This study provides a brief overview of the population most likely to experience a delay in the initiation of their adjuvant chemotherapy after cancer surgery. Our findings should assist interventions during initial management.

[Techniques and complications of non-genetic risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Modalités et morbidité des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation. DESIGN: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities. RESULTS: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation.

Delayed care for patients with newly diagnosed cancer due to COVID-19 and estimated impact on cancer mortality in France.

BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.

[Surgical management of breast cancer in outpatient versus overnight hospitalization: Satisfaction study]. / Prise en charge chirurgicale du cancer du sein ambulatoire versus hospitalisation d'une nuit : enquête de satisfaction.

OBJECTIVES: Breast cancer is the primary female cancer. In cancerology, it is essential to give to the patient some support. The advent of outpatient surgery optimizes the care path. This need for support of patients raises the question of its compatibility with the day surgery. The purpose is to compare the satisfaction of outpatients with those who stay overnight after surgery of breast cancer. MéTHODS: Patients who underwent breast conservative surgery were included. It is a mixed study, a quantitative, observational and prospective one using a satisfaction survey and a qualitative one which consisted on semi - directive individual interviews. We compared the satisfaction rate (highest marks). RESULTS: There were 91 patientes, 38 in the ambulatory group and 53 in the overnight group. There was no significant difference in satisfaction between the two groups (P=0.18). The difficulties frequently highlighted by the patients during their stay were the organizational management, the lack of hospital comfort and the sometimes long wait. The need for human support was unanimous. CONCLUSION: The satisfaction was excellent in the study. The mode of hospitalization does not seem to play a role here on satisfaction. This hospitalization mode can only be envisaged by providing sufficient human and technical resources. Enhanced recovery after surgery appears to be an alternative to outpatient surgery.

Radiofrequency ablation of retained placenta accreta after conservative management: preliminary evaluation in the pregnant ewe and in normal human placenta in vitro.

OBJECTIVE: To evaluate radiofrequency (RF) efficiency and safety for the ablation of retained placenta in humans, using a pregnant sheep model. DESIGN: Experimental study. SETTING: Laboratory of Surgery School, Nancy, France. POPULATION/SAMPLE: Three pregnant ewes/ten human placentas. METHODS: Various RF procedures were tested in pregnant ewes on 50 placentomes (individual placental units). Reproducibility of the best procedure was then evaluated in a further 20 placentomes and on ten human term placentas in vitro after delivery. MAIN OUTCOME MEASURES: Placental tissues destruction, lesions' size, myometrial lesions. RESULTS: Low power (100 W) and low target temperatures (60 degrees C) lead to homogenous tissue destruction, without myometrial lesion. No significant difference was observed in terms of lesion size and procedure duration for in the placentomes of pregnant ewe in vivo and in human placentas in vitro. The diameter of the ablation could be correlated with the tines deployment. CONCLUSION: The placental tissue structure is very permissive to RF energy, which suggests that RF could be used for the ablation of retained placenta, providing optimal control of tissue destruction. These results call for further experimental evaluations.

[Atypical ductal and lobular hyperplasia of the breast]. / Hyperplasies atypiques du sein.

Atypical hyperplasia represents 4% of all benign breast diseases. There are two different types: atypical ductal hyperplasia and atypical lobular hyperplasia. Aside columnar cell lesion. They represent an early stage of some forms of low grade carcinoma in situ and invasive carcinomas. Atypical hyperplasia is a benign lesion with intermediate carcinologic risk and the existence of a concomitant aggressive lesion should be suspected. When atypical lesion is found on a biopsy specimen, surgical excision is recommended especially in case of atypical ductal hyperplasia. A regular supervision is recommended.

[Role of sentinel node biopsy in early-stage cervical cancer in the therapeutic strategy]. / Place du ganglion sentinelle dans la stratégie thérapeutique du cancer du col de l'utérus aux stades précoces.

Early-stage cervical cancer (IA2 and IB1) treatment consists in surgery with a radical colpohysterectomy associated to a systematic pelvic lymphadenectomy more or less a paraaortic lymphadenectomy (Wertheim-Meigs surgery). Pelvic lymph node involvement is the main independent prognostic factor and justifies an adjuvant therapy. Sentinel lymph node (SLN) procedure allows a reliable evaluation of the lymph node status thanks to an accurate histologic analysis. This procedure is still not validated in practice, which means the bilateral pelvic lymphadenectomy is systematically done whatever the lymph node status is. Nevertheless the purpose of the SLN biopsy in cervical cancer does not consist in avoiding an unnecessary lymphadenectomy, which is not really associated with a major morbidity. Actually, a better initial stadification would allow to fit to the risk of recurrence not only the radicality of the surgery, but also the adjuvant therapy. The morbidity of a radical surgery could be limited for good prognosis patients and avoided for the benefit of a concomitant chemoradiotherapy.

[Radioguided occult lesion localization in breast cancer (ROLL): new techniques?]. / Techniques préopératoires de repérage isotopique des lésions infracliniques mammaires (Trilim) dans les cancers du sein: techniques d'avenir?

Radioguided occult lesion localisation (ROLL) is a new technique which allows identification of non palpable breast lesion in breast cancer using, on the model of sentinel node procedure, injection of a radiotracer over the tumour lesion. With a gamma detection probe, it is then possible during surgery to identify in the same time the lesion and the sentinel lymph nodes. Compared with the wire-guided localisation (WGL), ROLL seems easier to achieve for radiologists, the excision procedure seems to be simpler with a good lesions resection in sano rate and a good cosmetic result.

[Parturients vaginal childbirth, social handicap and length of stay: pilot study at the Lariboisière Fernand-Widal Hospital Group in Paris]. / Parturientes accouchant par voie basse, handicaps sociaux et durée de séjour : étude pilote au groupe hospitalier Lariboisière-Fernand-Widal de Paris.

OBJECTIVES: Would a social handicap questionnaire with French DRG (PMSI) make it possible to know social disability parturients vaginal childbirth in a public health loss of revenue by increasing the average length of stay during the hospitalization of patients precarious? PATIENTS AND METHODS: The questionnaire of the social handicap consisted of 14 indicators associated to classify at the admission each patient in three categories of social handicap. RESULTS: The administration of a questionnaire of social handicap was carried out for 127 women giving birth by low way. Three quarters of the studied population have a strong social handicap and 18% present a means of it. The more social handicapped patients do not represent an additional cost for the establishment in terms of supplementary day of hospitalization. CONCLUSION: French DRG (PMSI) and indicators of precariousness can be used to locate the patient having social handicap. The consistency of the public action between the medical one and the social one are questioned.

[Synchronous bilateral breast cancer: risk factors, diagnosis, histology and treatment]. / Cancers du sein bilatéraux synchrones: facteurs de risque, diagnostic, histologie, traitement.

OBJECTIVE: Synchronous bilateral breast carcinoma (SBBC) is not uncommon. Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The purpose of this study was to evaluate risk factors, diagnostic circumstances, histological characteristics and therapeutic methods for SBBC. PATIENTS AND METHODS: Between July 1992 and May 2006, 62 patients with SBBC were treated at Tenon hospital (Paris, France). Population was divided into two sub-groups corresponding with two successive periods. Epidemiological characteristics, diagnostic circumstances, therapeutic methods and histological characteristics were analysed. RESULTS: Global incidence of SBBC during this period was 2.6%. The patients presenting a CSBS had a family antecedent of breast cancer in 23.7% of the cases. The most frequent situation associated a palpable tumour and an infraclinic contralateral lesion (43.5%). MRI made diagnosis possible in seven tumours. Among the patients 38.7% had a bilateral mastectomy and 33.9% profited from the technique of the ganglion sentinel. The proportions of invasive lobular carcinomas and the multifocal tumours were 17.7%. The tumours had the same histological type in 78.3% of the cases and the expression of oestrogen receptors was identical in 91.4% of the cases. DISCUSSION AND CONCLUSION: The principal risk factors of CSBS are a family history of breast cancer, the histological type lobular invasive and the multifocal character of the first tumour. A conservative surgery is possible as well as the use of the technique of the ganglion sentinel. The CSBS have histological similarities, probably due to environmental factors.

[Sentinel lymph node biopsy under local anaesthesia: how to avoid the disadvantages of intraoperative examination?]. / Le prélèvement du ganglion sentinelle sous anesthésie locale ou comment s'affranchir des limites de l'analyse histologique peropératoire.

The sentinel lymph node procedure has become the standard in the surgical management of localised breast cancer. However, it is submitted to the uncertainties of intraoperative examination. Indeed, intraoperative examination has three major disadvantages: the type of histological method (frozen section versus imprint cytology), the size of sentinel node metastasis (macro- versus micrometastases) and the time requested for this technique. All of these limits are responsible for secondary re-interventions to complete axillary lymph node dissection. Few medical teams have described a new surgical strategy to avoid these limits. They proposed the detection of the sentinel lymph node under local anaesthesia and to wait for the definitive histological analysis before carrying out lumpectomy and axillary lymphadenectomy if necessary under general anaesthesia. We realized a review of the literature on this new procedure to evaluate its feasibility and to assess the technical aspects.

[Seroma after axillary lymph node dissection in breast cancer]. / Prise en charge des lymphocèles après curage axillaire dans le cancer du sein.

Since the advent of sentinel node biopsy, which made it possible to reduce the morbidity of axillary surgery, axillary lymph node dissection has been constituting the treatment of reference in certain cases of breast cancer. One of the most frequent complications in the immediate postoperative period is the lymphocele or seroma, the frequency of which is independent of the axillary technique of surgery. Following an analysis of the literature, some risk factors were isolated such as a high body mass index, the high volume of the first three days drainage and arterial hypertension. Some techniques seem to show a benefit in the reduction of the lymphocele: sentinel node biopsy, padding of the axilla and the axillary drainage. The majority of other techniques such as the use of fibrin sealant, hemolymphostatic sponges, various techniques of axillary dissection, external axillary compression, differed mobilization from the upper limb, axillary dissection by lipo-aspiration and endoscopic axillary dissection, have too contradictory results at the present time to be recommended in clinical practice. No consensus is clearly established to decrease the incidence and the volume of the seroma after axillary dissection in breast cancer. Today, two techniques can be nevertheless distinguished: sentinel node biopsy and padding of the axilla.

[Interest of preoperative lymphoscintigraphy on sentinel lymph node identification in patients with breast cancer]. / Intérêt de la lymphoscintigraphie dans la procédure du ganglion sentinelle en cancérologie mammaire.

Sentinel lymph node biopsy is nowadays an accepted method of staging breast cancer patients. In case of an injection of radioactive colloid, preoperative lymphoscintigraphy is recommended to establish a lymphatic mapping and to predict the number of sentinel lymph nodes identified during surgery. Preoperative lymphoscintigraphy does not decrease the false-negative rate. However, positive preoperative lymphoscintigraphy significantly improves the identification rate of intraoperative sentinel nodes comparing with negative preoperative lymphoscintigraphy. Detecting extra-axillary sentinel lymph nodes, because of its minimal therapeutic consequences, does not appear to be an indication for preoperative lymphoscintigraphy. Given logistics and cost required, preoperative lymphoscintigraphy should be only performed for patients with a high risk of intraoperative failed localization. In case of negative preoperative lymphoscintigraphy, sentinel lymph node biopsy must be tried because sentinel nodes are still identified in the majority of these patients. Another possibility, with important cost and logistic, should consist in performing a later lymphoscintigraphy on the day after radioactive injection to ameliorate sentinel lymph nodes identification.

[Role of mifepristone for the treatment of uterine fibroid]. / La mifépristone dans la prise en charge des fibromes utérins.

Mifepristone, a progesterone receptor antagonist steroid, can reduce uterine fibroid tumours' growth by several pathways. Its efficiency has been widely evaluated in symptomatic patients for more than 10 years. A significant decrease in fibroid tumours and uterine volume concomitant with better quality of life scores can be obtained with a daily administration of Mifepristone 5mg. Mifepristone can be compared with GnRH agonists in terms of efficiency. Observed adverse outcomes are hot flushes (38%), elevated hepatic enzymes (4%) and benign endometrial hyperplasia (28%). Hot flushes and endometrial hyperplasia are not observed with 5mg daily doses. Data suggest that many invasive procedures could be avoided with the routine use of Mifepristone for fibroid tumours care. However, published study periods are only three to 12 months: long lasting evaluation in larger groups of patients seems necessary before this treatment could be proposed as routine care.

[Borderline ovarian tumors: an update]. / Tumeurs borderline de l'ovaire : état des lieux.

Borderline ovarian tumors account for 15-20% of all ovarian epithelial tumors and are diagnosed primarily in young women who want to preserve their childbearing potential. Due to the absence of specific preoperative criteria, diagnosis is often made during surgery or after the anatomopathologic examination. The management of borderline ovarian tumors with early stage is well-known and conservative surgery must be chosen as much as possible. Laparoscopic approach is possible for these tumors, allowing diagnosis, staging and also treatment. For advanced stage, laparotomy is still recommended. Staging must be performed during the initial surgery because tumor stage is one of the most relevant prognostic factors. Restaging operation should be discussed when complete staging was not made during initial surgery. Because his prognostic and therapeutic impacts are not proved, restaging surgery remains controversial. For that reason, it seems important to define clinical and histological criteria for patients with a high risk of upstaging.