[Identification and management of hereditary breast-ovarian cancers (2004 update)]. / Identification et prise en charge des prédispositions héréditaires aux cancers du sein et de l'ovaire (mise à jour 2004).

BACKGROUND: Since the last recommendations, up to 2500 new references had been published on that topic. METHODOLOGY: On the behalf of the health Minister, the Ad Hoc Committee consisted of 13 experts carried out a first version revisited by five additional experts who critically analyzed the first version of the report. MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer deleterious mutations of BRCA1 and BRCA2 than previously thought. The screening of ovarian cancer is still not an attractive option while in contrast MRI may be soon for these young women with dense breast, the recommended option for breast cancer screening. The effectiveness of prophylactic surgeries is now well established. French position is to favor such surgeries with regard to a quality of life in line with the expected benefit, and providing precise and standardized process described in the recommendation. CONCLUSIONS: Due to methodological flaws, the low power and a short follow-up of the surveys, this statement cannot however aspire to a high stability.

[Sonographic diagnosis of ovarian tumors: pre-operative Doppler evaluation]. / Apport du doppler pour le diagnostic des tumeurs ovariennes. Indications, pertinence des critères diagnostiques.

Pelvic sonography is the gold standard for diagnosis of ovarian masses. Only 2% of adnexal masses or malignant or bordeline tumors. Does Doppler US improve the diagnostic accuracy of sonography? The purpose of this article is to review current data and identify what areas still require further evaluation with regards to Doppler characterization of adnexal masses. It has been shown that Doppler evaluation of the ovary and cyst or tumor improves the diagnostic accuracy of US to differentiate between benign and malignant lesions. Hemodynamic data collected from pulsed Doppler imaging and Doppler energy vascular mapping have been shown to improve the characterization of malignant lesions. These data improve the accuracy of B-mode US combined with clinical evaluation and CA125 measurement. Nonetheless, the sensitivity and specificity values are between 85-90%, with few missed malignancies, but several false positive results. Useful Doppler data include the resistive index and the central intratumoral location of vascular flow. The use of 3D US with computer post-processing as well as sonographic contrast agents could provide additional information, but these techniques have not yet been validated. All suspicious adnexal lesions should be evaluated by an experienced sonographer and include discriminatory parameters to distinguish between benign and malignant lesions.

Color Doppler energy prediction of malignancy in adnexal masses using logistic regression models.

OBJECTIVE: The aim of this study was to assess the usefulness of color Doppler energy in the preoperative diagnosis of ovarian malignancy using multivariate logistic regression analysis. METHODS: One hundred and thirty adnexal masses were studied with transvaginal B-mode, color energy, and pulsed Doppler ultrasonography before surgery in order to develop a model that could be used to determine malignancy. Each ultrasonographic variable (tumor size, wall thickness, septal structure, echogenicity, papillary projection, density (solid or not)) was included individually or combined together as part of the Sassone ultrasound score. Intratumoral blood flow velocity waveforms were obtained to determine pulsatility index and resistance index and a more subjective parameter, location of tumor vascularity, was also assessed. Menopausal status and serum CA 125 levels were also entered as categorical variables. Sonographic parameters were entered alone, then associated with menopausal status and CA 125 serum levels, and finally with Doppler energy measurements. Our model was then validated in a group of 68 adnexal masses and compared to the model of Alcazar. RESULTS: Eighteen adnexal masses (13.8%) were malignant or of low malignant potential. Multivariate analysis showed that papillary projection of the tumor wall, cyst with solid parts, resistance index with a cut-off value of 0.53, CA 125, and central blood flow location, were the only factors to be independent predictors of malignancy. Menopausal status was not an independent factor. For the final model including the Doppler energy parameter the best sensitivity and specificity were 83% and 93%, respectively, at a cut-off value of 10% probability of malignancy compared to 83% and 87% for the morphological variables alone. Validation of the model showed its diagnostic performance to be as good as that reported in the original population and better than the model of Alcazar. CONCLUSION: Sonographic analysis of adnexal masses including color Doppler energy shows the best predictive properties according to histological diagnosis, and improves preoperative diagnosis of malignancy.

Characterization of the fertility of Kit haplodeficient male mice.

The role of the proto-oncogene Kit expression during gonadal development, then in differentiated spermatogonia has been thoroughly established. The present study was designed to investigate the consequences of a partial defect in Kit gene expression on sperm fertilizing ability, using Kit haplodeficient mice (kitW-lacZ/+). Same inbred mice (kit+/+) were used as controls. Epididymal sperm characteristics and in vivo fertility were assessed, then in vitro-fertilization experiments were carried out for mice of both genotypes. Epididymal sperm count was drastically reduced, and sperm motility was also decreased in kitW-lacZ/+ compared with kit+/+ males. Both in vivo or in vitro fertility were greatly reduced in kitW-lacZ/+ compared with kit+/+ males. By contrast, the fertility of kitW-lacZ/+ females was apparently unaffected. Additionally, a higher number of spermatozoa with undetected acrosomal contents was revealed by fluorescein isothiocyanate-labelled Pisum sativum agglutinin acrosomal staining after epididymal sperm retrieval in kitW-lacZ/+ mice, whereas no difference was observed after induction of acrosomal reaction in mice of either genotype. Ultra-structural data confirmed the higher frequency of abnormal acrosome in spermatozoa of kitW-lacZ/+ mice. Thus, sperm production is impaired in Kit haplodeficient mice both on a quantitative and a qualitative basis. Finally, we show that one single copy of Kit gene is not sufficient to maintain genuine fertility in male mice.

Histologic multifocality is predictive of skin recurrences after conserving treatment of stage I and II breast cancers.

OBJECTIVE: To distinguish various types of local recurrence after conserving treatment of breast cancer and to evaluate their predictive value. MATERIALS AND METHODS: We first researched the pronostic factors after local recurrence and second evaluated the predictive factors of skin and inflammatory recurrences out of a series of 605 cases of stage I and stage II breast cancer of less than 4 cm in diameter that occurred after conserving treatment. RESULTS: Multivariate analysis revealed two major predictors of poor prognosis associated with recurrence: early appearance Hazard ratio 3.0 (1.28-7.00) (p = 0.011) and inflammatory or skin involvement Hazard ratio 3.38 (1.36-8.45) (p = 0.009). A local recurrence multiplied the relative risk for metastasis by 2.6. This result depended on the type of recurrence: when those with inflammatory and cutaneous types were excluded, local recurrence was no longer a poor prognostic factor. Patients who experienced primary invasive tumor with histologic multifocality have a 4.08 (1.44-11.59) (p < 0.004) times greater risk of developing cutaneous or inflammatory recurrences compared with patients who experienced breast cancer unique localization. CONCLUSION: As histologic multifocality is the only factor predictive of dark prognosis local breast cancer recurrences, aggressive therapy at the time of the primary treatment could be the therapeutic implications of such finding on the original tumor.

[Maternal anxiety induced by prenatal diagnostic techniques: detection and management]. / Anxiété maternelle induite par les techniques de diagnostic prénatal: reconnaissance et prise en charge.

Recent improvement in the screening for chromosomal defects, in particular the widespread use of ultrasonography and maternal biochemistry, is leading to a high number of fetal invasive tests (amniocentesis or chorion villus sampling). An increased level of anxiety in the pregnant women, which may sometimes continue until the postnatal period, is believed to be due to these prenatal diagnosis procedures. Maternal anxiety originates in the doubts related to fetal integrity and pregnancy outcome after information of a positive biochemical screening or visualisation of an ultrasound marker of chromosomal abnormality. Each specialist involved in prenatal care should take special attention to this, because of at least two reasons. First, anxiety may reduce maternal well being during pregnancy. Second, because it could have deleterious effects on parent to infant relationships. Without any intention of lowering the positive aspects of prenatal diagnosis, it appears essential to consider the negative effects anxiety may have on both parents. From our own experience and the conclusion of previous reported studies, we suggest some measures to reduce the level of maternal anxiety related to prenatal diagnosis: (i) improvement in the quality and transparency of information offered to pregnant women; (ii) training and involvement in psychological and emotional care for each member in the medical team; (iii) special and systematic psychological care for the "high risk" pregnant women regarding anxious disorders.

[Borderline tumors of the ovary: a multicenter study in 137 patients]. / Tumeurs borderline de l'ovaire: Etude multicentrique a propos de 137 patientes.

OBJECTIVES: Evaluate management of patients with a borderline ovarian tumor. MATERIALS AND METHODS: A multicentric retrospective survey was conducted in 137 patients with borderline ovarian tumor diagnosed between January 1, 19975 and December 31, 1995. RESULTS: Mean follow-up was 6.5 years, mean age was 50 years. Initial surgery was cystectomy, unilateral salpingo-oophorectomy and total hysterectomy with bilateral salpingo-oophorectomy in 22, 40 and 75 cases respectively. Eleven patients had residual disease. Serous, mucinous and Brenner tumors were observed in 67, 69 and 1 cases respectively. Staging was I, II, III in 117, 3, and 17 cases respectively with two pseudomyxomas. Adjuvant therapy was given in 15 patients. There was a recurrence in 15 patients and 14 died. The 5-year survival rate was 89.3%. Prognosis factors with an impact on survival rate were age, recurrence and type of surgery. Factors with a negative impact on recurrence were adjuvant therapy and residual disease after surgery. CONCLUSION: Careful staging followed by complete and radical surgery is essential. Unilateral salpingo-oophorectomy with omentectomy and multiple peritoneal biopsies may be indicated in younger patients undergoing radical surgery after pregnancy. Aduvant therapy is necessary for invasive implants.

[Incidence, diagnosis and prognosis of ovarian metastasis in breast cancer]. / Incidence, diagnostic et pronostic des métastases ovariennes du cancer du sein.

Ovarian metastasis are frequently encountered during the course of breast cancer, concerning one woman in five among those suffering from the disease. These secondary ovarian lesions are usually small and bilateral with a non-cystic pattern and are more likely to be from primary infiltrating lobular carcinoma of the breast. Distinction between ovarian metastasis and primary ovarian cancer may sometimes be difficult and require immunohistochemical stains with various monoclonal antibodies. Primary ovarian cancer remains preponderant however, even in a woman with breast cancer. From a clinical point of view, ovarian metastasis are frequently unknown except in case of peritoneal dissemination. Trans-vaginal ultrasonography scan is the best examination when clinical signs give cause to suspect ovarian tumour. Although, systematic ultrasonography screening, as well as blood screening program using CA 125 and CA 15-3, should not be recommended because they lack sensibility and are too expensive. The development of ovarian metastasis during the course of a breast primary carcinoma is a negative prognostic factor with regards to the presence or absence of peritoneal dissemination.

[Standards, options, and recommendations for the radiotherapy of patients with endometrial cancer. FNCLCC (National Federation of Cancer Campaign Centers) and CRLCC (Regional Cancer Campaign Centers)]. / Standards, Options et Recommandations pour la radiothérapie des patientes atteintes de cancer de l'endomètre.

OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

Low body mass index is an independent predictive factor of local recurrence after conservative treatment for breast cancer.

BACKGROUND: Obesity or increased body mass index (BMI) has been shown to have two important adverse effects related to breast cancer. First, several studies have identified an association between increased BMI and advanced stage breast cancer. Second, increased BMI has been shown to be associated with poorer prognosis. In a previous report, we had identified low BMI as a risk factor for local reccurence at five years. The objectives of this study were to evaluate the relationship between BMI and local control and to confirm this prognostic factor in a larger population with an important follow-up. MATERIALS AND METHODS: Between 1976 and 1988, 605 women with invasive breast carcinoma less than 4 cm in diameter underwent conservative surgery with axillary dissection and radiation therapy. The median follow-up time was 82 months. The risk of local recurrence and distant metastasis was evaluated by univariate retrospective analysis using Kaplan-Meier method for the main clinical and histologic factors. Those found to be significant were entered in a Cox model for multivariate analysis. RESULTS: Since the beginning of the study, 80 patients had developed local recurrence. The 5 years and 10 years local control rates were 91% and 83%, respectively. Four parameters were independent predictive factors of local recurrence: Age lower than 40 years (HR = 2.42 95% CI = [1.35-4.34]), BMI: elevation of one unit reducing the local recurrence of 0.92 95%CI = [0.85-0.99], multifocality of the tumor on pathological examination (HR = 2.12 95% CI = [1.16-3.88]) and positive axillary nodes HR = 0.54 95% CI = [0.31-0.95]. Size of the breast was not a predictive factor for local cancer recurrence. Low BMI did not increase risk of distant. CONCLUSION: Our study offers new data concerning the possibility that thinness may be related to local recurrence of breast cancer.

[Standards, Options and Recommendations for the surgical management of carcinoma of the endometrium]. / Standards, Options et Recommandations pour la prise en charge chirurgicale des patientes atteintes de cancer de l'endomètre.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.