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.

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.

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.

[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.

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.

[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.

Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy.

BACKGROUND: Initial findings of the Italian Randomized Tamoxifen Prevention Trial found no reduction in risk of breast cancer with tamoxifen use, whereas the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial showed that tamoxifen treatment reduces risk of estrogen receptor-positive breast cancer. Here we present an extended follow-up of the Italian trial. METHODS: From October 1, 1992, to December 31, 1997, 5408 otherwise healthy women who had undergone hysterectomy were randomly assigned in a double-blind manner to tamoxifen (20 mg daily) or placebo for 5 years. Rates of breast cancer and other events in the two groups were compared by the use of risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: After 11 years of follow-up, 136 women (74 placebo, 62 tamoxifen) developed breast cancer (RR = 0.84, 95% CI = 0.60 to 1.17; annual rates were 2.48 and 2.07 per 1000 women-years, respectively). The rates of breast cancer in the two study groups were similar among women who had had bilateral oophorectomy and among women at low risk for hormone receptor-positive (HR+) disease but were much lower in the tamoxifen group among women at high risk (placebo, 6.26 per 1000 women-years, tamoxifen, 1.50 per 1000 women-years; RR = 0.24, 95% CI = 0.10 to 0.59). During the treatment period, women in the tamoxifen group reported more hot flashes (RR = 1.78, 95% CI = 1.57 to 2.00), vaginal discharge (RR = 3.44, 95% CI = 2.90 to 4.09), and urinary disturbances (RR = 1.52, 95% CI = 1.23 to 1.89) but fewer headaches (RR = 0.68, 95% CI = 0.50 to 0.94) than women in the placebo group. Hypertriglyceridemia (RR = 4.33, 95% CI = 1.96 to 9.53), thromboembolic events (RR = 1.63, 95% CI = 1.02 to 2.62), and cardiac arrhythmia or atrial fibrillation (RR = 1.73, 95% CI = 1.01 to 2.98) were also more frequent in the tamoxifen group than in the placebo group. CONCLUSIONS: Appropriate selection of women at high risk for HR+ disease may improve the risk-benefit ratio of tamoxifen intervention.

Dietary and lifestyle determinants of mammographic breast density. A longitudinal study in a Mediterranean population.

High mammographic breast density (H-MBD) has been associated with increased breast cancer (BC) risk, even after adjustment for established BC risk factors. Only a few studies have examined the influence of diet on MBD. In a longitudinal study in Florence, Italy, we identified about 2,000 women with a mammogram taken 5 years after enrollment, when detailed information on dietary and lifestyle habits and anthropometric measurements had been collected. Original mammograms have been identified and retrieved (1,668; 83%), and MBD was assessed by 2 experienced readers, according to Wolfe's classification and a semiquantitative scale. By logistic analysis, we compared women with H-MBD (P2 + DY according to Wolfe's classification) with those with low-MBD (N1 + P1). H-MBD was confirmed to be inversely associated with BMI, number of children and breast feeding, while it was directly associated with higher educational level, premenopausal status and a previous breast biopsy. In multivariate analyses adjusted for non-dietary variables, H-MBD was inversely associated with increasing consumption of vegetables (p for trend = 0.005) and olive oil (p for trend = 0.04). An inverse association was also evident between H-MBD and frequent consumption of cheese and high intakes of beta-carotene, vitamin C, calcium and potassium (p for trend < or = 0.05). On the other hand, we found a positive association with increasing consumption of wine (p for trend = 0.01). This large longitudinal study, the first carried out in Mediterranean women, suggests that specific dietary components may play a key role in determining MBD in this population, thus possibly modulating BC risk.

Early diagnosis, not differential treatment, explains better survival in service screening.

Italian population-based breast cancer screening programmes with 2-year, high-quality mammography started in the cities of Florence and Turin in the early 1990s. Breast cancer cases from the local Tumour Registry were classified by method of detection and tumour characteristics (size, nodal-status and grade). Follow-up was at December 2001. In total, 4444 breast cancer cases were analysed. The Hazard Ratio comparing before and after-invitation breast cancer cases indicated a 27% reduction (HR=0.73; 95%CI: 0.61-0.87) in the risk of dying for the disease. After adjustment for tumour characteristics, survival rate was comparable by invitation status, whereas the proportion of early cancer was 33.7% and 46.6% in the before and after-invitation group. Survival rates by tumour characteristic subgroups was comparable by invitation status. Late stage and grade 3 were indicators of poor prognosis. Adjustment for tumour characteristics confirmed screening and not differential treatment as the most important reason for the observed survival benefit. The survival analysis by specific subgroups did not support the hypothesis that the difference in prognosis was attributable to differential treatment.

Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial.

BACKGROUND: Tamoxifen, a selective estrogen-receptor modulator, increases venous thromboembolic events (VTE), but the factors explaining this risk are unclear. Atherosclerosis may induce VTE, or the 2 conditions may share common risk factors. We assessed the effect of tamoxifen on VTE in a breast cancer prevention trial and studied its association with risk factors for VTE. METHODS AND RESULTS: The incidence of VTE was studied in 5408 hysterectomized women randomly assigned to tamoxifen 20 mg/d or placebo for 5 years. There were 28 VTEs on placebo and 44 on tamoxifen therapy (hazard ratio [HR]=1.63; 95% confidence interval [CI], 1.02 to 2.63), 80% of which were superficial phlebitis, accounting for all of the excess due to tamoxifen within 18 months from randomization. Compared with placebo, the risk of VTE on tamoxifen was higher in women aged 55 years or older, women with a body mass index > or =25 kg/m2, elevated blood pressure, total cholesterol > or =250 mg/dL, current smoking, and a family history of coronary heart disease (CHD). Of the 685 women with a CHD risk score > or =5 who entered the trial, 1 in the placebo arm and 13 in the tamoxifen arm developed VTE (log-rank P=0.0013). In multivariate regression analysis, age > or =60 years, height > or =165 cm, and diastolic blood pressure > or =90 mm Hg had independent detrimental effects on VTE risk during tamoxifen therapy, whereas transdermal estrogen therapy concomitant with tamoxifen was not associated with any excess of VTE (HR=0.64; 95% CI, 0.23 to 1.82). CONCLUSIONS: Women with conventional risk factors for atherosclerosis have a higher risk of VTE during tamoxifen therapy. This information should be incorporated into counseling women on its risk-benefit ratio, particularly in the prevention setting.

Comparison of standard reading and computer aided detection (CAD) on a national proficiency test of screening mammography.

OBJECTIVE: To evaluate the role of computer aided detection (CAD) in improving the interpretation of screening mammograms MATERIAL AND METHODS: Ten radiologists underwent a proficiency test of screening mammography first by conventional reading and then with the help of CAD. Radiologists were blinded to test results for the whole study duration. Results of conventional and CAD reading were compared in terms of sensitivity and recall rate. Double reading was simulated combining conventional readings of four expert radiologists and compared with CAD reading. RESULTS: Considering all ten readings, cancer was identified in 146 or 153 of 170 cases (85.8 vs. 90.0%; chi(2)=0.99, df=1, P=0.31) and recalls were 106 or 152 of 1330 cases (7.9 vs. 11.4%; chi(2)=8.69, df=1, P=0.003) at conventional or CAD reading, respectively. CAD reading was essentially the same (sensitivity 97.0 vs. 96.0%; chi(2)=7.1, df=1, P=0.93; recall rate 10.7 vs. 10.6%; chi(2)=1.5, df=1, P=0.96) as compared with simulated conventional double reading. CONCLUSION: CAD reading seems to improve the sensitivity of conventional reading while reducing specificity, both effects being of limited size. CAD reading had almost the same performance of simulated conventional double reading, suggesting a possible use of CAD which needs to be confirmed by further studies inclusive of cost-effective analysis.