The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status. RESULTS: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. CONCLUSIONS: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.

The requirements of a specialist breast centre.

This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.

Microinvasive breast carcinoma: An analysis from ten Senonetwork Italia breast centres.

BACKGROUND AND OBJECTIVES: We studied a large series of ductal carcinoma in situ with microinvasion (MIDC) an infrequent disease whose diagnosis and management are not well defined. METHODS: 17,431 cases of breast carcinoma were treated between 2011 and 2016 by ten Italian Breast Units. Our analysis included diagnostic and clinic-pathological characteristics, surgical management, and the use of adjuvant therapies. RESULTS: 15,091 cases (86.6%) were infiltrating carcinomas (IC), 2107 (12.1%) ductal carcinoma in situ (DCIS), and 233 (1.3%) MIDC. Age at diagnosis did not differ between DCIS and MIDC. MIDC were usually larger and expressed more frequently biologically aggressive features (higher Ki67 values, hormone receptor negativity and HER2/neu over-expression) (p < 0.01). Axillary lymph nodes were involved in 25 MIDC cases (12%), but >3 lymph nodes were involved in two cases only (1%). At multivariable analysis, only lymphovascular invasion (LVI) was associated with lymph node status (p < 0.01). Hormone therapy was prescribed in 388/1462 DCIS cases (26.5%), in 84/200 MIDC cases (42%), and in 11,086/14,188 IC cases (84.7%) (p < 0.01). Chemotherapy was administered in 28/190 MIDC cases (14.7%), and in 4080/11,548 IC cases (35.3%) (p < 0.001). CONCLUSIONS: This is one of the largest studies of MIDC reported in the literature. Approximately 10% of DCIS harbor one or more foci of MIDC, and the latter often expresses aggressive biological features. LVI is a predictor of axillary node involvement, but this is infrequent and usually limited. Conservative surgery is performed less often than in DCIS, and adjuvant chemotherapy is less frequently utilized compared to IC.

Quality indicators in breast cancer care: An update from the EUSOMA working group.

In 2010, EUSOMA published a position paper, describing a set of benchmark quality indicators (QIs) that could be adopted by breast centres to allow standardised auditing and quality assurance and to establish an agreed minimum standard of care. Towards the end of 2014, EUSOMA decided to update the paper on QIs to consider and incorporate new scientific knowledge in the field. Several new QIs have been included to address the need for improved follow-up care of patients following primary treatments. With regard to the management of elderly patients, considering the complexity, the expert group decided that, for some specific quality indicators, if centres fail to meet the minimum standard, older patients will be excluded from analysis, provided that reasons for non-adherence to the QI are specified in the clinical chart and are identified at the review of the clinical records. In this way, high standards are promoted, but centres are able to identify and account for the effect of non-standard treatment in the elderly. In the paper, there is no QI for outcome measurements, such as relapse rate or overall survival. However, it is hoped that this will be developed in time as the databases mature and user experience increases. All breast centres are required to record outcome data as accurately and comprehensively as possible to allow this to occur. In the paper, different initiatives undertaken at international and national level to audit quality of care through a set of QIs have been mentioned.

Glycemic index, glycemic load and mammographic breast density: the EPIC Florence longitudinal study.

A few studies have evaluated the association between diet and mammographic breast density (MBD) and results are inconsistent. MBD, a well-recognized risk factor for breast cancer, has been proposed as a marker of cumulative exposure to hormones and growth factors. Diets with a high glycemic index (GI) or glycemic load (GL) may increase breast cancer risk, via an effect on the insulin-like growth factor axis. We have investigated the association between carbohydrate intake, GI, GL and MBD in a prospective study. We identified a large series of women, in the frame of the EPIC-Florence cohort, with a mammogram taken five years after enrolment, when detailed information on dietary and lifestyle habits and anthropometric measurements had been collected. Mammograms have been retrieved (1,668, 83%) and MBD assessed according to Wolfe's classification. We compared women with high MBD (P2+DY Wolfe's categories) with those with low MBD (N1+P1) through logistic models adjusted for age, education, body mass index, menopause, number of children, breast feeding, physical activity, non-alcohol energy, fibers, saturated fat and alcohol. A direct association between GL and high MBD emerged in the highest quintile of intake in comparison with the lowest quintile (OR = 1.73, 95%CI 1.13-2.67, p for trend = 0.048) while no association with glycemic index was evident. These results were confirmed after exclusion of women reporting to be on a diet or affected with diabetes, and when Hormone Replacement Therapy at the date of mammographic examination used to assess MBD was considered. The effect was particularly evident among leaner women, although no interaction was found. A positive association was suggested for increasing simple sugar and total carbohydrates intakes limited to the highest quintiles. In this Italian population we observed an association between glycemic load, total and rapidly absorbed carbohydrates and high MBD. These novel results warrant further investigations.

Fluctuating mastectomy rates across time and geography.

In 2009, 2 single-institution studies from the United States reported increasing mastectomy rates during the last decade. We have recently reported unilateral mastectomy trends from a European database and demonstrated a significant trend of decreasing mastectomy rates from 38.1 % in 2005 to 13.1 % in 2010. A recent study from the SEER registry in the United States confirmed a previously reported decrease in mastectomy rates from 40.1 % in year 2000 to 35.6 % in 2005, but showed a statistically significant increase in mastectomy rates up to 38.4 % in 2008. This report provides evidence that mastectomy trends may be in opposite directions in different geographical areas. The sharpest increase in mastectomy rates across all ages in the recent SEER study occurs right after year 2005, which interestingly corresponds with the time of publication of the meta-analysis by the EBCTCG that highlighted the importance of local control in breast cancer. The coincident timing raises the question of whether this evidence may have indirectly triggered an increase in mastectomy rates in the United States that would partially explain the observed trend, and more importantly, of whether an increase would be justified on this basis. Multiple factors influence the proportion between mastectomy and breast conservation, so it may be unreasonable to think of an optimal cutoff. There is not necessarily a right or wrong direction for mastectomy trends, but aiming to determine explanations for these differences may help provide a clearer insight of the decision-making process involved in the surgical management of breast cancer.

Mastectomy trends for early-stage breast cancer: a report from the EUSOMA multi-institutional European database.

INTRODUCTION: Recent single-institution reports have shown increased mastectomy rates during the last decade. Further studies aiming to determine if these reports could be reflecting a national trend in the United States of America (US) have shown conflicting results. We report these trends from a multi-institutional European database. PATIENTS AND METHODS: Our source of data was the eusomaDB, a central data warehouse of prospectively collected information of the European Society of Breast Cancer Specialists (EUSOMA). We identified patients with newly diagnosed unilateral early-stage breast cancer (stages 0, I or II) to examine rates and trends in surgical treatment. RESULTS: A total of 15,369 early-stage breast cancer cases underwent surgery in 13 Breast Units from 2003 to 2010. Breast conservation was successful in 11,263 cases (73.3%). Adjusted trend by year showed a statistically significant decrease in mastectomy rates from 2005 to 2010 (p = 0.003) with a progressive reduction of 4.24% per year. A multivariate model showed a statistically significant association of the following factors with mastectomy: age < 40 or ≥ 70 years, pTis, pT1mi, positive axillary nodes, lobular histology, tumour grade II and III, negative progesterone receptors and multiple lesions. CONCLUSION: Our study demonstrates that a high proportion of patients with newly diagnosed unilateral early-stage breast cancer from the eusomaDB underwent breast-conserving surgery. It also shows a significant trend of decreasing mastectomy rates from 2005 to 2010. Moreover, our study suggests mastectomy rates in the population from the eusomaDB are lower than those reported in the US.

Cancer guideline development in Europe: a survey among ECCO members.

A survey was conducted among European Cancer Organisations by the European CanCer Organisation (ECCO) to evaluate initiatives on cancer guideline development. An electronic questionnaire based on the 'Appraisal of Guidelines Research and Evaluation' (AGREE) instrument was sent to different ECCO members and other Scientific European Organisations involved in cancer care. Between April 2010 and July 2010, 30 European Cancer Organisations (ECOs) were contacted and 21 responded to the questionnaire. Of these, 13 were involved in the production of clinical practice guidelines. The majority of the cancer guidelines were treatment or disease-management related (84.6%). The objectives were appropriate clinical care (76.9%), cost containment (7.7%) or both (23.1%). Almost all organisations developed guidelines for their members but more than half were also aimed at policy makers (53.9%). In 69% of cases, the guidelines were developed according to specific instructions by searches in an electronic data base while in 46.2% there was a manual evaluation of the original articles. Disciplines almost always involved in guideline development groups were the medical and nursing specialities, while in some groups, communication specialists were always involved. Patients, as key stakeholders of the guidelines were involved by eight organisations in their development. The median costs for the development of a cancer guideline were between 25000 and 50,000 euro. This survey shows that many European cancer organisations are producing cancer guidelines. Since their development is both costly and time consuming, a coordinated approach should be encouraged.

The impact of different communication and organizational strategies on mammography screening uptake in women aged 40-45 years.

BACKGROUND: Several factors can influence access to population breast cancer screening. The aim of the study was to evaluate the impact of different information approaches, women's socio-demographic characteristics and organizational factors on mammography screening uptake. METHODS: We selected 5744 women aged 40-45 years who were randomly assigned to be given letters with: (i) a pre-fixed appointment plus standard leaflet (Group 1); (ii) a pre-fixed appointment plus a more comprehensive booklet (Group 2); (iii) point (ii) plus the offer of a counselling session (Group 3); and (iv) an invitation to contact the centre to get information and arrange participation (Group 4). RESULTS: Ninety-five women were excluded before the invitation and 5649 were randomized. After excluding undelivered letters (n = 41) and women reporting an exclusion criterion following our invitation (n = 248), the final eligible population was 5360 women. Participation rates following the first contact were 36.5, 39.9, 35.8 and 16.5% for Groups 1-4, respectively. The rates increased to 40.9, 43.6, 40.1 and 35.1% after the reminder letters. Women receiving more complete information had a higher uptake (Group 2), although not statistically significant. Differences among the four groups were maintained by controlling the effect of socio-demographic and attendance determinants. Regardless of intervention, participation was higher among married, higher educated, white-collared women, those born in northern Italy, living closer to the screening unit and with a female-collaborative doctor. CONCLUSION: Invitation letters with a fixed appointment correlate with a higher attendance rate. Providing women with more information on procedures, risks and benefits of mammography screening does not modify their participation.

Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group.

The use of breast magnetic resonance imaging (MRI) is rapidly increasing. EUSOMA organised a workshop in Milan on 20-21st October 2008 to evaluate the evidence currently available on clinical value and indications for breast MRI. Twenty-three experts from the disciplines involved in breast disease management - including epidemiologists, geneticists, oncologists, radiologists, radiation oncologists, and surgeons - discussed the evidence for the use of this technology in plenary and focused sessions. This paper presents the consensus reached by this working group. General recommendations, technical requirements, methodology, and interpretation were firstly considered. For the following ten indications, an overview of the evidence, a list of recommendations, and a number of research issues were defined: staging before treatment planning; screening of high-risk women; evaluation of response to neoadjuvant chemotherapy; patients with breast augmentation or reconstruction; occult primary breast cancer; breast cancer recurrence; nipple discharge; characterisation of equivocal findings at conventional imaging; inflammatory breast cancer; and male breast. The working group strongly suggests that all breast cancer specialists cooperate for an optimal clinical use of this emerging technology and for future research, focusing on patient outcome as primary end-point.

Audit system on Quality of breast cancer diagnosis and Treatment (QT): results of quality indicators on screen-detected lesions in Italy for 2006 and preliminary results for 2007.

Within this survey, conducted by the Italian Breast Screening Network (Gruppo Italiano per lo Screening Mammografico, GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2006, results showed overall good diagnosis and treatment quality and an improving trend over time. Critical issues were identified in waiting times, compliance with recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis reached the acceptable target, but there is a large variation between Regions and programmes. The sentinel lymph node technique (SLN) was performed on the axilla in more than 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN in ductal carcinoma in situ deserves further investigation. The detailed results have been distributed to regional and local screening programmes, also by means of an online database, in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume and enough resources would provide the best setting for making audit effective in producing quality improvement with a shortening of waiting times.

Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 tumour-suppressor genes predispose to early-onset breast and ovarian cancer. Although both genes display a highly heterogeneous mutation spectrum, a number of alterations recur in some populations. Only a limited number of founder mutations have been identified in the Italian population so far. OBJECTIVE: To investigate the spectrum of BRCA1/BRCA2 mutations in a set of families originary from the Central-Eastern part of Tuscany and to ascertain the presence of founder effects. We also wanted to approximate the age of the most frequent BRCA1 founder mutation. RESULTS: Overall, four distinct BRCA1 mutations accounted for a large fraction (72.7%) of BRCA1-attributable hereditary breast/ovarian cancer in families originary from this area. We identified common haplotypes for two newly recognised recurrent BRCA1 mutations, c.3228_3229delAG and c.3285delA. The c.3228_3229delAG mutation was estimated to have originated about 129 generations ago. Interestingly, male breast cancer cases were present in 3 out of 11 families with the c.3228_3229delAG mutation. CONCLUSIONS: The observation that a high proportion of families with BRCA1 alterations from Central-Eastern Tuscany harbours a limited number of founder mutations can have significant impact on clinical management of at risk subjects from this area. In addition, the identification of a large set of families carrying an identical mutation that predisposes to breast and ovarian cancer provides unique opportunities to study the effect of other genetic and environmental factors on penetrance and disease phenotype.

Physical activity and mammographic breast density in a Mediterranean population: the EPIC Florence longitudinal study.

A protective effect of physical activity (PA) on breast cancer (BC) risk has been suggested. Few studies have examined the influence of PA on mammographic breast density (MBD), a strong risk factor for BC. In a prospective study in Florence, Italy, we identified 2,000 healthy women with a mammogram taken 5 years after enrollment. Individual mammograms were retrieved (83%) and MBD assessed according to Wolfe's classification. Detailed information on PA at work and during leisure time, reproductive history, lifestyle and anthropometric measurements at enrollment were available for 1,666 women. Information on hormone replacement therapy (HRT) was also obtained at mammogram. Women with high-MBD (P2 + DY Wolfe's patterns) were compared with women with low-MBD (N1 + P1) by multivariate logistic models. Overall, high-MBD was inversely associated with increasing levels of leisure time PA (p for trend = 0.04) and among peri-/postmenopausal women, also with increasing levels of recreational activities (p for trend = 0.02). An interaction between PA and HRT emerged, with a stronger inverse association of highest level of recreational activity with MBD among HRT nonusers (p for interaction = 0.02). A modifying effect by body mass index (BMI) was evident among 1,025 peri-/postmenopausal women who did not use HRT at the time of mammogram, with a stronger inverse association between recreational PA and MBD in the highest BMI tertile (OR = 0.34; 95% CI 0.20-0.57; p for interaction = 0.03). This large study carried out in Mediterranean women suggests that leisure time PA may play a role in modulating MBD, particularly in overweight/obese peri-/postmenopausal women.

Audit system on quality of breast cancer diagnosis and treatment (QT): results of quality indicators on screen-detected lesions in Italy in 2005 and preliminary results for 2006.

Within this survey, conducted by the Italian Group of Mammography Screening (GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2005, results showed overall good diagnosis and treatment quality, and an improving trend over time. Critical issues were identified in waiting times, compliance with the recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis has reached the acceptable target, but room for improvement still exists. The sentinel lymph node technique (SLN) was performed on the axilla in more than 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed to local and regional screening programmes in order to allow multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volume would provide the best setting for making audit effective in producing quality improvement.

[Interval cancers as indicators of performance in screening programmes]. / I carcinomi di intervallo quali indicatori di performance di un programma di screening.

GISMa analyses the interval cancer (IS) topic providing guidelines and reference standards in addition to CE recommendations. IC identification is based on Cancer Registries (CR), if existing, or on hospital discharge records, in alternative. The optimal measure of IC frequency (inversely correlated with sensitivity) is the IC proportional incidence (observed IC/carcinomas expected in absence of screening). Other formulas (IC/IC + screen detected cancers; IC rate per 1000 negative screens) look less reliable. IC stage at diagnosis (if available through CR) must be compared with screen detected cancer and cancer detected in non-attenders. Review of mammograms preceding the IC (coded as screening error, minimal signs, or occult) should be done mainly with a blind procedure (IC mixed with negative controls), as this procedure is more representative of the original scenario and more respectful of radiologist's rights.

Does computer-aided detection (CAD) contribute to the performance of digital mammography in a self-referred population?

BACKGROUND: Recent evidence suggests that computer-aided detection (CAD) may have a negative impact on the interpretation of mammography-this necessitates timely evaluation of CAD in practice. We report a retrospective study of the incremental effect of CAD on the accuracy of full-field digital mammography (DM) as applied prospectively in breast assessment. METHODS: Subjects were all consecutive women attending a self-referral breast centre in Florence between September 2005 and January 2007 (N = 3,425). DM was reported without, then with, CAD according to a standard protocol; all mammograms recalled on the basis of either the radiologist's reading alone, or the radiologist's reading after viewing CAD, were recalled to assessment. RESULTS: Overall recall rate (RR) was 13.1% and 107 cancers were diagnosed (90 invasive cancers, 8 DCIS, 9 malignant on cytology). The use of CAD allowed the additional detection of 5 cancers (three invasive cancers, one DCIS, one malignant on cytology) and caused one additional benign surgical biopsy, with a relative RR of 4.9%, and an incremental RR of 1.17%. The cancer detection rate (CDR) of DM interpreted with the use of CAD was 3.12% and did not significantly differ from the CDR of 2.9% based on DM without CAD (chi(2) = 3.2, P = 0.07). CONCLUSION: While the increase in CDR with the use of CAD only approached statistical significance, representing modest gains in absolute terms, the incremental number of cancers detected justifies the incremental recall and benign surgical biopsy attributable to CAD use. In our clinical setting, these data suggest more benefit than harm in using CAD with DM, and we will continue the use of CAD with ongoing monitoring of patient outcomes.

Full-field digital versus screen-film mammography: comparative accuracy in concurrent screening cohorts.

OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy of digital mammography with that of screen-film mammography in concurrent cohorts participating in the same population-based screening program. MATERIALS AND METHODS: In a retrospective study covering 2004-2005, we compared digital with screen-film mammography in two concurrent screening cohorts of women 50-69 years old participating in a screening program operated from mobile units. Each cohort had 14,385 participants matched by age and interpreting radiologist from all participants consecutively registered. We compared recall and cancer detection rates. RESULTS: The recall rate was higher for digital mammography (4.56% vs 3.96%, p = 0.01), particularly when clustered microcalcifications were the only finding (1.05% vs 0.41%, p = 10(-6)) and for younger women (50-59 vs 60-69 years, 5.12% vs 4.17%, p = 0.009). The higher recall rate for digital mammography was mainly evident at incidence screening. The recall rate due to poor technical quality was lower with digital mammography (0.27% vs 0.50%, p = 0.002), possibly because real-time feedback was available. The detection rate was higher for digital mammography (0.72% vs 0.58%, p = 0.14), particularly for cancers depicted as clustered microcalcifications (0.26% vs 0.12%, p = 0.007), in younger (50-59 years) women (0.63% vs 0.42%, p = 0.09), and in denser breasts (1.09% vs 0.53%, p = 0.24). No significant difference was observed in positive predictive value on recall for digital mammography or screen-film mammography. Early cancer (pTis, pT1mic, pT1a) was more frequent in cancer detected with digital mammography than in that detected with screen-film mammography (41.3% vs 27.3%, p = 0.06). CONCLUSION: Digital mammography may be more effective than screen-film mammography in contemporary screening practice in mobile units. The data indicate that digital mammography depicts more tumors than does screen-film mammography, especially lesions seen as microcalcifications. The potential association with improved outcome warrants further study.

Audit system on quality of breast cancer diagnosis and treatment (QT): results from the survey on screen-detected lesions in Italy, 2004.

Within this survey, conducted by the Italian Group for Mammography Screening (GISMa), individual data are collected yearly on more than 50% of all screen-detected operated lesions in Italy. In 2004, overall results show a good diagnosis and treatment quality and an improving trend over time. Critical issues have been identified in waiting times, compliance to the recommendations on not performing frozen section examination on small lesions and on performing specimen X-ray. Pre-operative diagnosis has reached an acceptable level, but room for improvement still exists. The sentinel lymph node technique (SLN) was performed on the axilla in almost 70% of screen-detected invasive cancers, avoiding a large number of potentially harmful dissections. On the other hand, potential overuse of SLN deserves further investigation. The detailed results have been distributed to local and regional screening programmes in order to enable multidisciplinary discussion and the identification of appropriate solutions to any problems documented by the data. Specialist Breast Units with adequate case volumes would provide the best setting for effective audits leading to quality improvement.

[Recommendations of a national Italian consensus conference on the opportunity of extending screening service by mammography to 40-49 and 70-74 years of age women]. / Raccomandazioni di una conferenza di consenso italiana sull'opportunità di estendere lo screening mammografico organizzato alle donne di 40-49 e 70-74 anni di età.

The Italian Mammography Screening Network (GISMa) held a national consensus conference in Bologna, May 25-26 2006. The large panel of participants included national experts in fields related to breast cancer and screening issues. The final aim was the production of a consensus statement which might become a standard reference for Italy. The consensus document (http://www.gisma.it) states that full national coverage by organized screening for breast (age 50-69), cervical and colorectal cancer is a priority, before any extension of organized mammography screening to younger or older age groups may be considered. If adequate resources are available, extension of organized screening for breast cancer until age 74 is recommended, at least for regular attenders until age 69. Extension of organized screening to women aged 40-49 may be considered at some conditions: (a) that resources are available, (b) that a 1-year interval is adopted, (c) that proper information of the limitations of screening is given to participants and (d) that priority is given to age 45-49.