François Eisinger

Médecine personnalisée et cancer du sein : médecine anticipatoire, évaluation pronostique et ciblage thérapeutique

Breast cancer is now considered as a large collection of distinct biological entities, the management of which is increasingly personalized. Personalized medicine - defined as a medicine, which uses molecular profiles, notably genetic profiles, from patients and/or tumors to tailor therapeutic decisions - is now introduced in the management of breast cancer at any stages: screening and prevention of hereditary forms, prognostic and predictive evaluation of early breast cancer, and, more recently, novel clinical trials in advanced breast cancer, where genetic characterization of tumor tissue based on genomics, including next-generation sequencing tools, is used to drive specific therapeutic targeting.

Pharmaco-prévention et nutri-prévention des cancers de la prostate

In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.

Colon Cancer Screening Programs: Impact of an Organized Screening Strategy Assessed by the EDIFICE Surveys

BackgroundThe aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. Via the colorectal cancer screening program, all average-risk individuals in the 50–74-year age group are invited every 2xa0years to do a guaiac-based or, since April 2015, an immunochemical fecal occult blood test.MethodsThe fifth edition of the nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1299 individuals with no history of cancer (age, 50–74xa0years) was interviewed between 22 November and 7 December 2016. The present analysis focuses on minimum lifetime uptake of screening tests, compliance to recommended repeat-screening intervals, and reasons for non-participation.ResultsIn 2016, 64% survey participants had been screened at least once and 38% had been screened in the previous 2xa0years, suggesting a trend towards increasing participation rates, particularly in the younger age categories and among men. The 2016 data also suggest that the newly implemented FIT-based screening program has been well perceived by the population. Up to one in four individuals cited “no risk factors” as the reason for not undergoing screening. This reveals ignorance of the fact that the colorectal cancer screening program actually targets all average-risk individuals in a given age group, without individual risk factors. ConclusionWe suggest the next step should be dedicated to educational approaches to explain exactly what screening involves and to persuasive messages targeting those who to date have remained unreceptive to information campaigns.

Fluctuating Behavior of the French Population in Cancer Screening: 5th Edition of the EDIFICE Survey

BackgroundThe EDIFICE surveys have assessed cancer screening behavior in the French population since 2005.MethodsThe 2016 edition was conducted among a representative sample of 1501 individuals (age, 50–75xa0years). The current analysis focuses on breast, colorectal, prostate, lung, and cervical cancer screening.ResultsThe rate of women (50 to 74xa0years) declaring having had at least one breast cancer screening test in their lifetime remained stable and high between 2005 and 2016. Compliance with recommended screening intervals improved between 2005 and 2011 from 75 to 83%, respectively, then decreased significantly to 75% in 2016 (Pu2009=u20090.02). Uptake of at least one lifetime colorectal cancer screening test procedure declared (individuals aged 50–74xa0years) increase from 25% in 2005 to 59% in 2011, stabilized at 60% in 2014, then reached 64% in 2016. Opportunistic prostate cancer screening (men aged 50–75xa0years) rose between 2005 and 2008 from 36 to 49%, plateaued until 2014 then dropped to 42% in 2016. The proportion of women aged 50–65 declaring having undergone one cervical cancer screening test dropped significantly between 2014 and 2016 from 99 to 94% (Pu2009<u20090.01). Lastly, 11% of our survey population in 2014 and 2016 (55–74xa0years) declared having already undergone lung cancer screening.ConclusionCancer screening behavior fluctuates in France, regardless of the context, i.e., organized programs or opportunistic screening. This observation highlights the need for constant analysis of population attitudes to optimize public awareness campaigns.

Awareness and Misconceptions of Breast Cancer Risk Factors Among Laypersons and Physicians

BackgroundPrimary prevention of cancer relies on awareness of and consequent identification of risk factors. We investigated knowledge of breast cancer risk factors not only among laywomen but also among female physicians.MethodsThe EDIFICE 4 nationwide observational survey was conducted by phone interviews of a representative female population (737 laywomen and 105 female physicians) aged 40–75xa0years, using the quota method. This analysis focuses on spontaneous replies to the question “In your opinion, what are the five main risk factors that increase the risk of breast cancer?”.ResultsHeredity/Family history of breast cancer was the most widely recognized risk factor in both study populations (98.1% physicians vs. 54.2% laywomen; Pu2009≤u20090.01). Smoking (19.0 and 17.5%) and alcohol consumption (3.8 and 5.5%) were among the lifestyle risk factors that were cited by similar proportions of physicians and laywomen, respectively. Other established risk factors were however very rarely cited by either physicians or laywomen, e.g., Exposure to medical radiation (4.8 vs. 0.4%, respectively; Pu2009≤u20090.05) or not cited at all, i.e., Benign mastopathy and Personal history of breast cancer.ConclusionThis survey highlights a number of misconceptions relating to behavioral risk factors for breast cancer, including the relative impact of alcohol and tobacco consumption and the importance of menopausal status. The limited awareness of the risk related to Exposure to medical radiation, Benign mastopathy, or Personal history raises concern regarding compliance with national screening recommendations.

Beliefs and behavior regarding e-cigarettes in a large cross-sectional survey

Although e-cigarette use is increasing dramatically, numerous concerns persist regarding toxicity and their role in smoking cessation. We assessed beliefs and behavior regarding e-cigarettes in an adult French population. The 4th French nationwide observational survey, EDIFICE 4, was conducted among representative samples of 1602 laypersons (age, 40–75u202fyears) from 12 June-10 July 2014, using the quota method. Profile, beliefs and behavior were assessed by phone interviews of the participating lay population with no history of cancer (Nu202f=u202f1463). Tobacco use, nicotine dependence (Fagerström test) and e-cigarette use were assessed. E-cigarette users represented 6% of the study lay population. E-cigarette users regarded e-cigarettes as helpful for quitting tobacco smoking and reducing the risk of lung cancer. Current dual users (e-cigarettesu202f+u202fcigarettes) were more likely to attempt to quit than current exclusively cigarette smokers (odds ratio, 3.15 [1.74–5.70]), and to consider themselves at higher risk for lung cancer (OR 3.85 [2.47–5.99]). They also considered e-cigarette vapor to be less toxic than tobacco smoke in terms of both active and passive exposure. Dual users typically consider themselves at higher risk for cancer and intend to quit smoking. Physicians should be made aware of this specific sub-population for whom e-cigarettes may be a useful trigger in the smoking cessation process.

Familial breast cancer and DNA repair genes: insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing: Contribution of DNA repair genes in familial breast cancer

Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost‐effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious‐predicted variants in DNA repair genes in familial breast cancer (BC) in a well‐characterized and homogeneous population. We analyzed 113 DNA repair genes selected from either an exome sequencing or a candidate gene approach in the GENESIS study, which includes familial BC cases with no BRCA1 or BRCA2 mutation and having a sister with BC (N = 1,207), and general population controls (N = 1,199). Sequencing data were filtered for rare loss‐of‐function variants (LoF) and likely deleterious missense variants (MV). We confirmed associations between LoF and MV in PALB2, ATM and CHEK2 and BC occurrence. We also identified for the first time associations between FANCI, MAST1, POLH and RTEL1 and BC susceptibility. Unlike other associated genes, carriers of an ATM LoF had a significantly higher risk of developing BC than carriers of an ATM MV (ORLoF = 17.4 vs. ORMV = 1.6; p Het = 0.002). Hence, our approach allowed us to specify BC relative risks associated with deleterious‐predicted variants in PALB2, ATM and CHEK2 and to add MAST1, POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC susceptibility. We also highlight that different types of variants within the same gene can lead to different risk estimates.

Knowledge-Based Cancer Control

Cancer control requires a complex combination of prevention, screening, care, and rehabilitation. Optimal cost-effective management is based on adequate, timely allocation of resources that take individual differences into consideration. Which health services to offer, to whom, and at which moment are all key questions for public health policies and programs. Precision medicine, personalized care, prevention, and mass media campaigns nowadays work closely together to improve cancer control. Since 2005, the EDIFICE group has been committed to improving upstream interventions (prevention and screening) and, to this end, has conducted several nationwide surveys [1] that have provided compellingly robust data. Several factors play a significant role in the effectiveness of prevention and screening. Our surveys have focused mainly on laypersons’ attitudes and behavior, while hard data on the effectiveness of mammography, sensitivity, and specificity of the Pap smear and the predictive value of FOBT were sourced from other studies. We do not claim to provide data on all aspects of upstream interventions; our findings do however provide a clearer insight into the current situation and identify pitfalls to be avoided. As society evolves, so individual attitudes evolve as well, highlighting the necessity for healthcare authorities and professionals to have a finer awareness of the way in which each individual perceives his or her own risk understands the advantages and disadvantages of prevention and screening and feels compelled or not to comply with medical recommendations. Our ambition is that physicians, advocate groups, healthcare authorities, and agencies will benefit from the results and analyses of our survey data that will hopefully smooth the way to implementing innovative effective screening or prevention programs. To begin with, it is worth mentioning the context of our survey and also a number of methodological aspects. In France, there are two types of cancer screening: opportunistic screening and official organized programs that are described below:

Perception of Lung Cancer Risk: Impact of Smoking Status and Nicotine Dependence.

BackgroundThe general population is nowadays well aware that tobacco smoking dramatically increases the risk of developing lung cancer. We hypothesized that a personal history of smoking and the level of nicotine dependence in current smokers may affect the perception of this risk among healthy individuals.MethodsThe fourth French nationwide observational survey, EDIFICE 4, was conducted by telephone among a representative sample of individuals (Nu2009=u20091602) aged between 40 and 75xa0years. Interviewees were asked about their smoking habits, perception of the risk of lung cancer, and nicotine dependence (Fagerström test).ResultsRegardless of their smoking status or level of nicotine dependence, the majority (96%) of our study population (Nu2009=u20091463) acknowledged that tobacco smoking is a major risk factor for lung cancer. For 34% of all respondents, smoking ≤u200910 cigarettes per day does not carry any risk of lung cancer. Only half the current smokers considered themselves to be at higher risk of lung cancer than the average-risk population. The majority of current cigarette smokers with a nicotine dependence considered themselves to be at higher risk for lung cancer while only 37% of non-nicotine-dependent individuals had the same perception (Pu2009<u20090.01). Current smokers were more likely to consider a screening examination than former smokers and never-smokers. However, the intention to undergo screening was not significantly affected by the level of nicotine dependence.ConclusionsAwareness campaigns may first have to overcome misconceptions about light smoking and, secondly, to target specific populations (heavy smokers, those with a long history, highly dependent smokers).

Current and Former Smokers: Who Wants To Be Screened?

&NA; Participation is key to the success of cancer screening. Identifying the reasons for nonparticipation is therefore essential. The present analysis of the EDIFICE (etude sur le dépistage des cancers et ses facteurs de compliance [survey on cancer screening and compliance factors]) surveys (n = 1463) found 36.4% of current smokers and 26.3% of former smokers intended to participate in a lung cancer screening program. Discrepancies exist between the screening program target populations and the individuals who actually intend to undergo screening. Background: Lung cancer (LC) screening (LCS) with annual low‐dose computed tomography scans has been seen to reduce the specific and overall mortality in selected populations. However, participation is key to successful screening programs. The EDIFICE (etude sur le dépistage des cancers et ses facteurs de compliance [survey on cancer screening and compliance factors]) nationwide observational surveys are used to assess behavior related to cancer screening programs in France. Materials and Methods: Using comprehensive multivariate stepwise logistic regression analyses of data from current and former cigarette smokers, we sought to identify the explanatory factors associated with the intention to participate in an LCS program. Results: Of the 1463 respondents with no personal history of cancer, 263 (36.4%) of the current cigarette smokers and 170 (26.3%) of the former cigarette smokers stated their willingness to participate in an LCS program. The explanatory factors differed between current cigarette smokers (already screened for LC: odds ratio [OR], 2.81; < 30 pack‐years: OR, 2.69; intention to quit smoking: OR, 1.96; no social vulnerability: OR, 2.15) and former cigarette smokers (comorbidities: OR, 0.31). The usual eligibility criteria were not significantly explanatory. Conclusion: Our findings highlight the discrepancy that exists between target populations and individuals who actually intend to participate in a screening program for LC, with subsequent potential effects on the participation rates and, thus, on the efficacy of screening.