Marco Rosselli Del Turco

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.

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.

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 Wolfes classification and a semiquantitative scale. By logistic analysis, we compared women with H‐MBD (P2 + DY according to Wolfes 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 nondietary 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 β‐carotene, vitamin C, calcium and potassium (p for trend ≤ 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.

Independent Double Reading of Screening Mammograms

Objective — To evaluate the cost effectiveness of independent double reading of screening mammograms. Setting — Prospective study of 18817 women undergoing first or repeat screening in a population based programme in the Florence district. Methods — Mammograms were independently double read by experienced radiologists. Subjects with mammographic abnormalities reported by at least one reader were recalled for diagnostic assessment. The mean increase in recall rate, cancer detection rate, and screening costs attributable to double reading was calculated. Results — Eleven of 125 cancers were detected by only one reader. The mean increase in cancer detection rate attributable to double reading compared with single reading was 4·6% (95% confidence interval (CI) 1·1 to 8·9). From a total of 748 cases referred for diagnostic assessment, 196 subjects were referred by one reader only. The mean increase in referral rate attributable to double reading compared with single reading was 15·1% (CI 12·3 to 17·8). Double reading caused a marked increase in the cost for each woman screened −8·5% at the first screening and 6·2% at repeat screening and a more limited increase in the cost for each cancer detected −3·5% at the first screening and 2·7% at repeat screening. Cancers detected by only one screener were at an earlier stage than those detected by both screeners (P = 0·6, not significant). Conclusions — Independent double reading results in only a modest increase in the detection of cancers and therefore may not be cost effective.

Risk of breast cancer subsequent to proven gross cystic disease

3809 women in whom breast cysts were aspirated were followed up to evaluate the observed/expected ratio of subsequent breast cancer. Breast cancer at cyst aspiration was excluded by physical examination and mammography. The first year of follow-up was censored to avoid a prevalence screening effect. Subsequent breast cancers were found either directly or by means of a cancer registry which also provided the expected age and residence specific incidence rates. The number of expected cancers was assessed in person-years (15,915 in the total series). The observed/expected subsequent breast cancer ratio was 1.77 (34/19.15; 95% confidence interval 1.23-2.48, P less than 0.05). The presence of gross cysts was associated with a moderately though significantly increased risk of subsequent breast cancer. Increased surveillance in such patients is not justified.

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.

Effect of population-based screening on breast cancer mortality

Although the wider scientifi c community has long embraced the benefi ts of population-based breast screening, there seems to be an active anti-screening campaign orchestrated in part by members of the Nordic Cochrane Centre. These contrary views are based on erroneous interpretation of data from cancer registries and peerreviewed articles. Their specifi c aim seems to be to support a pre-existing opposition to all forms of screening. These individuals, making claims of poor methods, selectively discount overwhelming scientifi c evidence from numerous randomised trials in diff erent countries that organised screening reduces breast cancer mortality. They claim that the signifi cant decrease in breast cancer mortality achieved by screening is due to improvements in treatment alone, discounting the benefi ts of early detection. If true, this would imply that breast cancer is an exception among adenocarcinomas in that early detection does not improve prog nosis—a claim contrary to the evidence. For women with breast cancer, early detection also results in improved quality of life from less extensive surgical treatment. Women with screen-detected breast cancer in the UK have half the mastectomy rate of women with symptomatic cancers— ie, 27% versus 53%. Organised, high-quality breast screening is an important public health initiative by numerous governments worldwide. These policies are based on robust and extensive analysis of individualised patient data from scientifi c trials, with particular attention paid to the balance of potential benefi ts and harms. To imply that such an international action is mass misrepresentation, or that screening is done for the benefi t of self-interested professionals, is as perverse as it is unjustifi ed. Comprehensive guidelines deal with the entire screening process. Organisations responsible for screening programmes regularly review published evidence on the eff ects of mammographic screening, and also contradictory interpretations. We consider the interpretation by Jorgensen, Keen, and Gotzsche, of the balance of benefi ts and harms to be scientifi cally unsound. Women would be better served by focusing eff orts on how best, and not whether, to provide breast screening. The signatories below, charged with provision and implementation of breast screening in many diff erent countries, remain convinced that the scientifi c foundation for populationbased, quality-assured, organised breast screening is one of the major accomplishments of the translation of clinical cancer research into public health practice. Early detection, in combination with appropriate treatment, signifi cantly lowers breast cancer mortality and improves the life quality of patients with the disease.

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 enrolment. Individual mammograms were retrieved (83%) and MBD assessed according to Wolfes classification. Detailed information on PA at work and during leisure time, reproductive history, lifestyle and anthropometric measurements at enrolment were available for 1,666 women. Information on hormone replacement therapy (HRT) was also obtained at mammogram. Women with high‐MBD (P2 + DY Wolfes 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.

Referral policy and positive predictive value of call for surgical biopsy in the Florence Breast Cancer Screening Program.

The authors evaluate the referral rates and the predictive value (PV) of call for diagnostic work up or biopsy in a population based breast cancer screening program in the 1979-1986 period. The presence of mammographic abnormalities either benign or suspicious proved to be the only reliable referral criterion (recall rate = 7.9%, recall PV = 3.8%, biopsy call PV = 39%). When mammography was normal the presence of breast complaints other than pain or of a radiologically dense breast were aspecific referral criteria, and since the latter was abandoned, (a) referral rates dropped especially in younger women, (b) referral or biopsy PV improved, whereas (c) cancer detection rate was almost unaffected. Younger age was associated with higher referral rates and with lower PV of both referral or biopsy. Whenever comparison with previous examination was possible, mammography accuracy was higher; this explains the decrease in referral rates and the increased predictivity observed at further rounds with respect to first screening round.