Cancer screening in adults with down syndrome, a proposal.

BACKGROUND: The specific distribution of cancers in Down syndrome (DS) calls into question the validity of screening policies for cancer surveillance as implemented for the general population. METHODS: We performed a literature review of cancer screening opportunities for adults with DS, taking account of the tumor profile in this specific population. RESULTS: In DS, solid tumors in adults are at most half as common as in the overall group of persons with intellectual disabilities, who have a frequency similar to that of the general population. In women with DS, breast cancer is rare, the frequency of colorectal cancer is poorly described, and cervical cancer is rarely reported, although sometimes observed at an advanced stage. Young men have an increased risk of testicular cancer. DISCUSSION: We propose that adults with DS should participate in colon cancer screening. For women with DS, breast cancer screening is not recommended, but annual clinical monitoring should be conducted, with the option to perform ultrasound or MRI examination in suspect cases. For cervical cancer, screening could be proposed to women who are sexually active beginning at age 25 years. Annual surveillance for testicular cancer via palpation by a health professional is preferable from ages 15 to 45. In case of additional genetic predisposition in a person with DS, a surveillance similar to other family members is recommended. CONCLUSION: The specific tumor profile in DS warrants an adapted screening program for breast, colon, cervical and testicular neoplasia.

Harm Reduction or Harm Introduction? Prevalence and Correlates of E-Cigarette Use Among French Adolescents.

PURPOSE: Electronic cigarettes are marketed as a tool to give up or reduce cigarette smoking, and their use has risen sharply in recent years. There is concern that use is increasing particularly among adolescents and that they are not being used as a cessation tool but as a novel experience in their own right. METHODS: The present research assessed prevalence and sociodemographic correlates of e-cigarette use and standard cigarette use and also explored the extent to which e-cigarettes appear to be used as a cessation tool. This was assessed using a questionnaire administered to 1,486 French adolescents aged 16 years. RESULTS: Prevalence of e-cigarette experimentation was high (54%) and comparable to that for standard cigarettes (55%). Furthermore, 20% of those who had experimented with e-cigarettes had never tried standard cigarettes, and among regular smokers of standard cigarettes, intentions to quit were not associated with e-cigarette usage frequency. Experimentation with both e-cigarettes and standard cigarettes was significantly predicted by higher age, higher socioeconomic status, and parental smoking of standard cigarettes (in particular the father). Being male marginally predicted e-cigarette use, whereas being female significantly predicted standard cigarette use. CONCLUSIONS: These findings give cause for concern: e-cigarette usage experimentation is extremely high, and is not associated with attempts to quit smoking standard cigarettes. Rather, it is exposing adolescents to a highly addictive drug (nicotine) and may pave the way for a future cigarette habit.

Le cancer chez les déficients intellectuels: épidémiologie et prise en charge.

In France, people with intellectual disability (ID) account approximately for 2.5 % of the total population. Life expectancy of ID increased over the last years, and this raised the risk of cancers developing in this group of patients. Overall, the prevalence of cancers for those patients is much like that of the general population, but they have specificities regarding their epidemiology, diagnostic and treatment. The type of cancers occurring differs depending on the age and the etiology of the ID of the patient. ID may raise special difficulties for the management and the treatment of the cancer that may be, ultimately, non optimal.

[Chateaubriand and contemporary medicine]. / Chateaubriand et la médecine de son temps.

The author reviews the situation of medicine in the time of Chateaubriand, then his attitude toward this art and its practitioners, then his own pathology, psychological as well as somatic.

CaPSCA: Evaluation of a Brief Cancer Prevention Education Programme to Promote Balanced Diet in French School Children.

This study examined the effectiveness of two cancer prevention interventions in improving balanced diet among French children aged 12-14 years. The educational techniques used were taken from the taxonomy of behaviour change techniques (BCTs; Abraham & Michie, 2008). Allocation to intervention group (intervention versus control) was randomised at the school-level, the intervention group received two interventions, each of 1-h duration, containing BCTs including advocated attitude, anticipated success/regret, behaviour modelling and barrier identification. Self-reported diet was assessed pre- and post-interventions. The resulting data were coded by a nutritionist and transformed into a novel measure representing the extent to which the participant achieved a balanced diet. Multilevel modelling indicated that, having taken into account the clustered nature of the data, gender and the differing socio-economic status of the participants, balanced diet decreased over time, b=-1.23, t(1830)=-2.79, p=0.005, but this was qualified by a significant interaction effect with intervention, b=1.42, t(1830)=1.98, p=0.047. Separate models for each intervention group revealed that balanced diet decreased over time in the control group, b=-1.25, t(1195)=-2.47, p=0.014, but did not in the intervention group, b=0.19, t(635)=0.44, p=0.66, suggesting a buffering effect of the interventions on balanced diet over time. These findings demonstrate the effectiveness of educational interventions using established behaviour change techniques, to change behaviour.

[Organized colorectal cancer screening]. / Le dépistage organisé des cancers colorectaux.

Organized colorectal screening in France was extended to the whole of the country in 2008. People aged from 50 to 74 years are offered fecal occult blood tests (FOBT) every two years. Patients with individual or familial risk factors for colorectal disease are excluded from the program. Despite promotion campaigns, the participation rate remains low, at about 30 %. It has been decided that a quantitative immunogical test will replace FOBT in the near future. The evaluation and use of colonoscopy and recto-sigmoidoscopy as screening tests must be re-evaluated in the light of recent research findings.

[Organized breast cancer screening]. / Le dépistage organisé du cancer du sein.

Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to increase its efficiency, by targeting populations at a higher risk than the women currently included, and to reduce the number of mammograms done outside the program, as they are not subject to the same quality controls. Risks could be reduced by increasing the sensitivity of mammography and the specificity of the readings. Moreover, it is mandatory to inform women of both the benefits and risks of screening, in compliance with the principle of enabling patients to make a free and informed choice.

Predictors of intentions to eat healthily in 8-9-year-old children.

One thousand two hundred seventy-two French children aged 8-9 years old participated in a study aimed at identifying predictors of healthy eating intention. We used a survey based on the Theory of Planned Behavior (TPB). Regression analyses were performed to assess the extent to which the extended TPB variables explained intention to eat healthily. The results indicated that attitude, parental norms, friend's norms, knowledge, motivation to conform to friends' and parental norms and perceived behavioral control accounted for 35% of the variance of intention to eat healthily. The most important predictor in this study was perceived as behavioral control.

[How to reduce the incidence of breast cancer]. / Cancers du sein, incidence et prévention.

The incidence of breast cancer is rising in all industrialized countries. In France, with 41,000 new cases and 11,000 deaths per year, breast cancer is still the first cause of death from cancer in women. Genetic familial breast cancer is rare (only-2% due to mutated BRCA1/2 genes). Most of the increase is due to sporadic cases associated with hormonal, reproductive and nutritional factors, some of which can be avoided. Prevention should include: - avoidance of risk factors such as alcohol, obesity, smoking, sedentarity, and, when possible, late first pregnancies and absence of breast feeding. - Lesser use of hormone replacement therapy, in order to avoid the tumor-promoting action of ovarian hormones; this is supported by the strong fall in the incidence of breast cancer in U.S.A after 2002, following a drop in the use of HRT by post-menopausal women. - For very-high-risk women (BRCA 1/2 mutations, or in situ carcinoma with proliferative atypia), chemoprevention with SERM should be authorized, based on randomized trials of tamoxifen and raloxifen. New trials of other agents should be encouraged. - Risk indexes such as that developed by the NCI should be more widely used. - More research on the early steps of human mammary carcinogenesis should be encouraged, as this should lead to individual targeted prevention.

[Screening for occult malignancies (breast, colorectum, prostate) beyond the usual age limits]. / A propos du dépistage des cancers infracliniques (sein, colon, prostate) au-delà des limites d'âge consensuellement admises.

The utility of screening for occult malignancies in very elderly people is controversial. Indeed, the following factors must be taken into account: increasing life expectancy, better efficacy and tolerability of cancer therapies, the cost of screening, and medico-legal issues. The dilemma is between missing a curable cancer and over-diagnosing and over-treating a vulnerable patient. Proper patient information is clearly needed The informed patient's own preference is crucially important. This paper focuses on the most frequent malignancies that can be detected by screening, namely breast, colorectal and prostate cancer.

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results.

PURPOSE: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. METHODS AND MATERIALS: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m2 5-fluorouracil, 12 mg/m2 mitoxantrone, and 500 mg/m2 cyclophosphamide, with concomitant radiotherapy (50 Gy +/- 10-20-Gy boost). Patients in Arm B received 500 mg/m2 5-fluorouracil, 60 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. RESULTS: Median treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p = 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). CONCLUSIONS: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.

Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer.

CONTEXT: Adjuvant chemotherapy with new cytotoxic agents for breast cancer must be properly assessed for toxicity. OBJECTIVE: To describe adverse events associated with adjuvant chemotherapy for breast cancer, which led to premature termination of a clinical trial. DESIGN, SETTING, AND PATIENTS: We conducted a prospective randomized multicenter study (Reposant sur des Arguments Pronostiques et Predictifs [RAPP]-01) to compare the effectiveness of 2 chemotherapy regimens. Patients (women aged 18-70 years) had primary unilateral breast cancer and either a moderate number of positive axillary lymph nodes (< or =3) or no positive axillary lymph nodes (N0), but were at a high risk of relapse. Patients were treated at 11 French cancer referral centers from June 1999 through January 2003. Primary prophylaxis for febrile neutropenia was not recommended in the study protocol. INTERVENTIONS: Doxorubicin, 50 mg/m2, plus docetaxel, 75 mg/m2, or doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, given postoperatively for 4 courses. MAIN OUTCOME MEASURES: The main end point was the disease-free survival rate at 5 years, as estimated using the Kaplan-Meier product limit method. Secondary end points included safety, which is the focus of this article, and overall survival. RESULTS: A total of 627 women were enrolled. Median follow-up is currently too short (24 months) to analyze the primary end point. The trial was terminated prematurely when 2 deaths related to drug toxicity and 1 case of perforative peritonitis occurred among patients with febrile neutropenia, all in the doxorubicin-docetaxel group. The incidence of febrile neutropenia was significantly higher with the doxorubicin-docetaxel regimen (40.8%) than with the doxorubicin-cyclophosphamide regimen (7.1%) (P<.001). CONCLUSIONS: A high risk of life-threatening complications associated with the doxorubicin-docetaxel regimen was found in this open-label controlled trial. The doxorubicin-docetaxel combination should not be considered as an alternative to the doxorubicin-cyclophosphamide regimen outside carefully designed studies that include primary prophylaxis for febrile neutropenia.

[FDG (18 fluorodeoxyglucose) positron emission tomography and breast cancer]. / Tomographie par emission de positons (TEP) au FDG et cancer du sein.

Positron emission tomography (PET) is a metabolic radionuclide imaging method in which a tracer labeled with a positron emitter is detected with a dedicated system. 18F-fluorodeoxyglucose (FDG) accumulates in tumor cells because of their increased glycolytic activity, and is thus widely used as a tracer in oncology. This increased metabolic activity precedes morphologic modifications, making FDG-PET a very useful tool for detecting and staging cancer. It can also be used to characterize morphologic changes, differentiating not only between benign and malignant lesions, but also between viable tumor cells and areas of necrosis and/or fibrosis induced by treatments. Being a whole-body examination, it allows malignancies to be staged in a single procedure. Systems combining PET and CT (computed tomography) offer improved performance, providing both metabolic and anatomical data. This technique appears to be useful for initial breast cancer staging, especially of locally advanced forms and suspected recurrences (increase of isolated tumor marker). Early studies of PET evaluation of responses to hormonal and/or cytotoxic therapies have also given very promising results. However, this technique does not seem sufficiently sensitive to be included in the initial screening or diagnosis of primary tumors, owing to its limited resolution (about 5 mm) and its restricted availability. This approach is poorly sensitive when used for axillary assessment, but offers good specificity.

[Opinion of the French National Academy of Medicine on the legislative framework for the application of the European Directive on biomedical research in humans]. / Sur l'encadrement législatif des recherches biomédicales chez l'homme, à l'occasion de la transposition dans le droit français de la directive européenne.

The French National Academy of Medicine considers that biomedical research in humans is a necessity for Public Health. This research is indispensable to medical progress and public health. It must respect medical ethics, scientific rigor, and should be implemented within a legislative framework. The Academy is concerned by the insufficient French participation in this research, which is largely a result of the small number of patients included in therapeutic trials that are necessary to the progression of knowledge and the improvement of diagnosis and treatment. Such research should be encouraged and unjustified (or useless) constraints should be lifted, particularly those which weigh on studies whose goal is furthering knowledge and are independent from industry. It approves that in the proposed revision of the articles of the law regarding the protection of persons participating in biomedical research, the distinction between research with of without direct individual benefit is removed. It notes that trials known as "non-interventional," meaning tested trials (studies in which the drugs which are used are already authorized or which use tested therapeutic strategies) are not concerned by the directive. The Academy would like these trials to be better defined in order to avoid any ambiguity. It would like to see the creation of a registry of French trials as well as the rapid publication of epidemiological studies or therapeutic trials whose results could have important consequences for Public Health. The realization of large trials requires European cooperation, therefore the harmonization of legislation in the member States of the E.U. is a necessity; this should lead to the creation of a European structure of appeal in this field.

[Cost of treatment and follow up of breast cancer: a retrospective assessment in a comprehensive cancer centre]. / Evaluation rétrospective du coût du cancer du sein dans un centre de lutte contre le cancer.

CONTEXT: Breast cancer is one of the major causes of premature death for women. Its cost management is important for both the national health insurance and the individual health care providers. OBJECTIVE: The objective of this study was to assess the global medical cost of breast cancer from diagnosis to follow up in one French medical centre: centre René-Huguenin, Saint-Cloud (92). METHOD: Duration of medical activities and other medical resources utilisations were collected from a retrospective cohort of 120 patients followed from January 1995 to February 2000. Unit costs were obtained from cost accounts of the Centre. RESULTS: The mean medical cost per patient was FF 66,067 [60,318-7,815] (USD $ 10,744 [9,809-11,679]). The mean cost varied from FF 41,875 (UDS $ 6,810) to FF 81,020 (UDS $ 13,175) depending on choice of type of therapy. The initial treatment phase was the most expensive, costing FF 48,397 [46,176-50,617] (USD $ 7,870 [7,509-8,231]) which represented 73.3% of the global cost. CONCLUSION: This study has provided an estimate of the real global cost of managing patients with breast cancer in a single French Comprehensive Cancer Centre (CLCC). The study method used is readily transposable to other treatment contexts and to other types of cancer.