[HPV prophylactic vaccine coverage in France: Results of a survey among high school and university students in Marseilles' area]. / Évaluation de la couverture vaccinale du vaccin anti-hpv : résultats d'une enquête auprès des lycéennes et étudiantes de la région PACA.

OBJECTIVE: To assess HPV prophylactic vaccine coverage among French high school and university students as well as their level of education about this vaccine. PATIENTS AND METHODS: An anonymous survey was conducted among 2500 high school and university students from the area of Marseilles, France, from December 2009 to April 2010. RESULTS: A total of 2018 questionnaires were collected (80.7% participation rate). Mean age of participants was 20 years (range, 15-45 years). Only 671 (35.4%) participants reported having been vaccinated against HPV, of whom 510 (73.4%) had completed the three injections scheme. Practice of cytological cervical cancer screening was not significantly influenced by vaccination status. Thus, 578 (45.2%) participants who had not been vaccinated already had had a cervical cytology performed, versus 295 (43.3%) vaccinated ones (P=0.445). Among those not being vaccinated, 671 (49.8%) fulfilled criteria for a catch-up vaccination, of whom only 325 (48.4%) agreed for such a catch-up. Main reasons given for refusal for a catch-up vaccination were the lack of information about HPV vaccine and fear of side effects. In total, 1722 (90%) considered themselves as educated about the HPV vaccine. Source of education was attributed to doctors and media by 54.4% and 53.7% of participants, respectively. Educational role attributed to school and university was poor (3.4%). CONCLUSION: Despite apparent satisfactory level of education, HPV prophylactic vaccine coverage among high school and university students appears to be insufficient.

[Patients' preferences and decision-making: state of the art and applications in cancer]. / Préférences des patients et prise de décision : état des lieux et retour d'expérience en cancérologie.

BACKGROUND: This paper deals with the physician-patient encounter. In France, the current legal framework allows patients to be informed (patients' rights to health information) and to participate to decisions regarding their own health. In such a context, this paper aims to give the reader the broad key components of the so-called 'patient treatment preferences elicitation process' in breast cancer, our research area. METHODS AND RESULTS: We first present the general context, with a definition of the different physician-patient models. We then present decision aids, tools that aim to provide high-quality information to patients in the decision-making process. Finally, based on our previous studies and on examples drawn from the international literature, we present the empirical process of patients' preferences elicitation, which not only increases patients' knowledge of and satisfaction with the decision made, but also allows patients to be part of their disease management. CONCLUSION: Far from being a phenomenon in the air supported by a legal system, this method developed in the 90s allows patients and more generally healthcare users to be autonomous without constraining them to a choice.

[Oncoplastic technics with nipple-areolar complex resection for the treatment of central breast cancers]. / Chirurgie oncoplastique pour le traitement des tumeurs mammaires centrales.

Central breast cancer has long been an indication for mastectomy. Plastic surgical techniques adapted to cancer (oncoplastic surgery) have made it possible to offer breast cancer patients conservative surgery with resection of the nipple-areolar complex (NAC). We evaluated carcinologic results and cosmetic outcomes as a function of the oncoplastic technique used. We performed a retrospective study in 47 patients with central breast cancers undergoing breast-conserving with NAC resection. Carcinologic results were assessed by calculating local and metastatic recurrences rates. Cosmetic results were evaluated on four criteria assessed by the patient then by two surgeons. The mean age of the patients was 59.8 (44-84) years. The mean tumour diameter was 17.4 (6-39)mm. Histological involvement of the nipple is present in 53% of the cases. No local recurrence, neither death was observed at 4.5 years median follow-up. One patient had liver metastatic recurrence at 83 months. Cosmetic results were assessed in 33 patients. Round-block provided better aesthetic results: the shape of the breast was considered very good or satisfactory for 90% of the surgeons with the round-block technique and for 46% with transverse incision (P=0.02). Breast-conserving surgery is feasible in selected patients with T1 or T2 central breast cancers, with no impact on the risk of local recurrence. NAC resection is essential especially when the patients have clinical signs of nipple involvement. It provides satisfactory cosmetic results, especially with the round-block technique, possibly associated with nipple reconstruction using the "cat-design" technique developed by our team.

[Reattendance of women for breast cancer screening programs. A review]. / Participation secondaire des femmes au dépistage organisé du cancer du sein Revue de la littérature.

BACKGROUND: In France, breast cancer is the most frequently occurring cancer and the leading cause of cancer deaths in women. Breast cancer screening has been shown to reduce breast cancer mortality by 30% provided attendance rate is 70% and re-screening interval is two to three years. Maintaining a high rate of reattendance is also important. The decline with time of completion rates of re-screening will lessen the benefits of a breast cancer screening program. METHODS: A review of published studies examining factors associated with attendance and reattendance to breast cancer screening. RESULTS: Positive views about initial screening are determining factors in reattendance: mammography should not be painful and embarrassing, appointments should be punctual and clinic staff courteous and supportive. Psychological factors influencing attendance also influence reattendance as does intention to participate, a major predictor of repeat participation and as do perceived susceptibility of breast cancer, perceived benefits of mammography, absence of emotional barriers. These factors can be modified by experience of previous screening. Other predicting factors of attendance continue to influence reattendance: practice of other preventive health behaviors, outside support from physicians, knowledge of breast cancer and screening. CONCLUSION: A better understanding of factors influencing attendance is necessary to increase the impact of breast cancer screening. Field studies are necessary to support the elaboration of publicity campaigns aimed at increasing participation.

[Knowledge and preferences of the patients about medical information: a study on 700 patients in a regional comprehensive cancer centre]. / Connaissances et préférences des patients sur le droit à l'information médicale: enquête auprès de 700 patients dans un centre régional de lutte contre le cancer.

Information is an important part of the patient care in oncology. The role and objectives of patient information were determined by a law passed in March 2002. This study investigates the knowledge of the patients about their rights and their views on what they consider most important. Information about health status and treatments is considered a priority (92.8% of respondents). The majority of patients whish to be given every information about their disease and treatments. On the contrary only 6.7% would rather receive less precise information tailored to what they want to know. Keeping control on the communication of their health information to relatives and other doctors is the option preferred by the majority of patients. Fifty two per cent of the persons are reluctant to be given medical information on the telephone. However opinions differ among social classes since 62% of patients from the upper classes consider it positively. This study demonstrates that the 2002 law is, in its broad outlines, a good response to patient's information needs.

Keeping data continuous when analyzing the prognostic impact of a tumor marker: an example with cathepsin D in breast cancer.

The prognostic value of cathepsin D has been recently recognized, but as many quantitative tumor markers, its clinical use remains unclear partly because of methodological issues in defining cut-off values. Guidelines have been proposed for analyzing quantitative prognostic factors, underlining the need for keeping data continuous, instead of categorizing them. Flexible approaches, parametric and non-parametric, have been proposed in order to improve the knowledge of the functional form relating a continuous factor to the risk. We studied the prognostic value of cathepsin D in a retrospective hospital cohort of 771 patients with breast cancer, and focused our overall survival analysis, based on the Cox regression, on two flexible approaches: smoothing splines and fractional polynomials. We also determined a cut-off value from the maximum likelihood estimate of a threshold model. These different approaches complemented each other for (1) identifying the functional form relating cathepsin D to the risk, and obtaining a cut-off value and (2) optimizing the adjustment for complex covariate like age at diagnosis in the final multivariate Cox model. We found a significant increase in the death rate, reaching 70% with a doubling of the level of cathepsin D, after the threshold of 37.5 pmol mg(-1). The proper prognostic impact of this marker could be confirmed and a methodology providing appropriate ways to use markers in clinical practice was proposed.

Altered expression of DNA double-strand break detection and repair proteins in breast carcinomas.

AIMS: To determine whether the expression of DNA damage detection and repair proteins is frequently altered in breast carcinomas. METHODS AND RESULTS: The expression profiles of five such proteins: ATM, p53, NBS1, MRE11 and Rad50 were analysed in 99 in-situ and invasive ductal breast carcinomas of different grades using an immunohistochemical approach, and compared with those seen in eight independent non-cancer (normal) breast samples and in the surrounding normal tissues of the breast carcinomas examined. ATM protein expression was reduced in 75% of the tumours compared with the levels found in normal tissues. Fewer tumours had reduced protein levels of the members of the MRE11, NBS1 and Rad50 (MNR) complex (31%, 46% and 28%, respectively) with p53 being over-expressed in 30%. In the majority of tumours (92%) we observed a good correlation between the expression of the three proteins of the MNR complex with low NBS1, MRE11 or Rad50 expression rarely found alone, suggesting that this event occurs subsequently to the deregulation in expression of other DNA repair proteins. CONCLUSION: The pattern of protein changes observed supports our hypothesis that alterations in DNA double-strand break repair capacity are involved in mammary carcinogenesis.

Axillary lymph-node dissection for positive sentinel nodes in breast cancer patients.

AIM: The aim was to identify a subset of breast cancer patient with positive sentinel nodes (SNs) for whom secondary axillary clearance would be unnecessary. METHODS: Between March 1999 and May 2001, 288 patients with T0-T2 breast cancer less than 3cm in diameter had SN detection either by a colorimetric method or using a combined technique. SNs were stained with haematoxylin and eosin (H&E). For all negative SNs, serial sections and immunochemistry (IHC) were performed. All patients with positive SNs underwent a complete axillary lymph node dissection. One hundred and twenty patients were SN positve. RESULTS: Non-sentinel node positivity (NSNP) was closely associated with the size of the tumour (14.3%, 54.1% and 51.8% for pT1a-b, pT1c and pT2 tumours respectively) and with the size of the SN metastasis: 15.9% IHC detected micrometastasis, 33.3% and 78.8% micro- and macrometastasis detected with H&E staining respectively. NSNP was found in 24.0% and 42.8% of patients with pT1c breast cancer and with micrometastasis detected by IHC and H&E staining. The node positivity rate reached 81.1% for pT1c lesions with macrometastasis in the SN. For the patients with pT2 breast cancer, these rates were 12.5% (IHC), 28.5% (H&E) 91.1% (macrometastasis). CONCLUSIONS: We are unable to isolate precisely a subset of patients for whom total axillary lymph node dissection would be unnecessary. A subset of 14 small tumours (<1cm diameter) demonstrated micrometastases in the SN without NSNP.

Tubulin detyrosination is a frequent occurrence in breast cancers of poor prognosis.

Tubulin, the dimeric subunit of microtubules, is a major cell protein that is centrally involved in cell division. Tubulin is subject to specific enzymatic posttranslational modifications including cyclic tyrosine removal and addition at the COOH terminus of the alpha-subunit. Tubulin is normally extensively tyrosinated in cycling cells. However, we have previously shown that detyrosinated tubulin accumulates in cancer cells during tumor progression in nude mice. Tubulin detyrosination, resulting from suppression of tubulin tyrosine ligase and the resulting unbalanced activity of tubulin-carboxypeptidase, apparently represents a strong selective advantage for cancer cells. We have now analyzed the occurrence and significance of tubulin detyrosination in human breast tumors. We studied a total of 134 breast cancer tumors from patients with or without known complications over a follow-up period of 31 +/- 10 months. The mean age of the patients at the time of diagnosis was 57 years. For each patient, detailed data concerning the histology and extension of the tumor were available. Tumor cells containing detyrosinated tubulin were visualized by immunohistochemical staining of paraffin-embedded tissue sections. Cancer cells with detyrosinated tubulin were observed in 53% of the tumors and were predominant in 19.4% of the tumors. Tubulin detyrosination correlated to a high degree of significance (P < 0.001) with a high Scarf-Bloom-Richardson (SBR) grade, a known marker of tumor aggressiveness. Among SBR grade 1 tumors, 3.8% were strongly positive for tubulin detyrosination compared with 65.4% of the SBR grade 3 tumors. The SBR component showing the strongest correlation with tubulin detyrosination was the mitotic score. In the entire patient population, neither the SBR grade nor the detyrosination index had significant prognostic value (P = 0.11, P = 0.27, respectively), whereas a combined index was significantly correlated with the clinical outcome (P = 0.02). A preliminary subgroup analysis indicated that tubulin detyrosination may define high- and low- risk groups in breast cancer tumors with an SBR grade of 2. Our study shows that tubulin detyrosination is a frequent occurrence in breast cancer, easy to detect, and linked to tumor aggressiveness.

[How to evaluate the quality of information transfer from physician to patient? Choice of psychometric tests for a decision tree in a Regional Cancer Centre]. / Comment évaluer la qualité du transfert de l'information du médecin au patient? Le choix des tests psychométriques d'un tableau de décision dans un Centre Régional de Lutte contre le Cancer.

BACKGROUND: Decision boards are used to transfer information from physicians to patients to help them participate in the clinical decision-making process. We present the tests and results of the psychometric properties of a decision board in a sample of healthy volunteers. METHODS: In the Regional Cancer Centre located in Lyon, we developed a decision board for post-menopausal women with breast cancer after lumpectomy without any poor prognostic factors. Two treatment options were proposed, one involving chemotherapy and the other not. We tested for the following psychometric properties: comprehension, construct validity and reliability. Comprehension was evaluated using a questionnaire, in order to test whether the rates of correct answers were due to chance alone. The construct validity was assessed by changing the information provided (relapse and survival rates, characteristics of chemotherapy) and testing whether the proportion of healthy volunteers choosing an option changed in a predictable and significant way. The reliability was evaluated using the test-retest method. Two reliability statistics were computed: the Pearson correlation and the Intraclass Correlation Coefficient. RESULTS: In the sample of 40 healthy volunteers, 23 chose the option with chemotherapy and 17 the option without chemotherapy. Results show that the decision board was comprehensive, valid (the women changed their choices in a predictable way) and reliable (Pearson correlation and Intraclass Correlation Coefficient close to 1). CONCLUSION: The choice of the psychometrics properties tested and the statistical tests used are discussed. The psychometric properties of our tool are found to be satisfactory.

[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.

Shared decision-making in question.

Over recent years, communication within the physician-patient relationship has been profoundly changing. New modes of conveying diagnostic and therapeutic information influence the way in which decisions regarding treatment are made. We propose a critical review of the various theoretical models as presented in the literature, from the paternalistic to the shared decision model, in order to reveal conceptual ambiguities and their related methodological problems. This analysis leads to a project for clarifying these problems through a research protocol based on shared decision-making.

[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.

Lymphatic mapping and sentinel node biopsy of operable breast cancer.

The aim of this study was to evaluate the reliability and accuracy of sentinel node biopsy for invasive breast cancer and the predictability of axillary node status. Between January 1996 and June 1997 a total of 73 patients underwent patent blue dye lymphatic mapping and sentinel node biopsy followed by standard (level I and II) axillary node dissection (one bilateral procedure). The sentinel node was identified in 82.4% (61/74) of the cases and was predictive of axillary status in 96.7% (59/61). The false-negative rate of the procedure was 8.0% (2/25). The sentinel node was involved in 37.7% (23/61) and was the only one invaded in 30.4% (7/23). The sensitivity of the procedure was 92% (CI95% 74-99%) and its specificity 100%. It is currently considered to be an attractive new procedure undergoing evaluation in prospective controlled trials. This study confirmed the reliability and reproducibility of intraoperative lymphatic mapping and sentinel node biopsy. This is the first step toward a new era of minimally invasive axillary surgery for breast cancer.

Abnormal expression of the ATM and TP53 genes in sporadic breast carcinomas.

The ataxia telangiectasia gene (ATM) has been implicated as a risk factor in the development of sporadic breast carcinomas. ATM protein expression was analyzed by immunohistochemistry in 17 breast carcinomas with two monoclonal antibodies whose immunohistochemical use was first validated by comparing the immunoreactivity observed in spleen samples from ataxia telangiectasia and trauma patients. In normal breast ducts, ATM showed nuclear expression in the epithelial but not in the myoepithelial cells. In contrast, this nuclear expression was absent or low in the epithelial cancer cells in 10 of 17 (59%) of the tumors studied. Allelic imbalance in the ATM gene was found in three of seven tumors examined. Two of these showed reduced ATM protein expression, but this did not correlate with the presence of ATM mutations in the tumor DNA detected by restriction endonuclease fingerprinting screening. These results suggest that the reduced ATM protein expression could be attributable, in certain tumors, to deletions or rearrangements within or close to the ATM gene. Positive p53 immunostaining was found in 10 tumors, with TP53 mutations detected in 8. Three tumors had both low ATM expression and mutated TP53. Our results indicate that in the majority (15 of 17) of the sporadic breast carcinomas examined, not only is the functionality of the ATM-p53-mediated DNA damage response compromised, but also other signaling pathways activated by these two multifunctional proteins are likely to be impaired, which could be a contributing factor to tumor development and progression.