Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

Physical characteristics of five clinical systems for digital mammography.

The purpose of this study was to evaluate and compare the physical characteristics of five clinical systems for digital mammography (GE Senographe 2000D, Lorad Selenia M-IV, Fischer Senoscan, Agfa DM 1000, and IMS Giotto) currently in clinical use. The basic performances of the mammography systems tested were assessed on the basis of response curve, modulation transfer function (MTF), noise power spectrum, noise equivalent quanta (NEQ), and detective quantum efficiency (DQE) in an experimental setting closely resembling the clinical one. As expected, all the full field digital mammography systems show a linear response curve over a dynamic range from 3.5 to 500 microGy (0.998

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Computer-aided detection (CAD) of cancers detected on double reading by one reader only.

We evaluated the role of computer-aided detection (CAD) in cancers undergoing double reading and detected by one reader only. A series of 33 cancers, originally missed by the first reader and detected by the second reader, and 75 negative controls were processed to assess CAD sensitivity, and was read by the six radiologists who originally missed the cancers with the help of CAD printouts. CAD case-based sensitivity, specificity and positive predictive value were 51.5%, 18.6% and 21.7%, respectively. Average sensitivity of all radiologists in all cancers in the series was 74.7%, being higher for CAD+ (86.2%) than for CAD- (62.5%) cancers (P<0.01). When reading cancer cases that they had originally missed, radiologists had a sensitivity of 75.8%, which was higher for CAD+ (100.0%) than for CAD- (58.3%) cancers. The average recall rate was 14.2%, the majority of recalls (45 out of 64) occurring for lesions marked by CAD. CAD may help in detecting at most half of cancers missed at a single reading but detected by a second reader.

Second reading of screening mammograms increases cancer detection and recall rates. Results in the Florence screening programme.

OBJECTIVE: To assess double reading effectiveness in mammography screening. DESIGN: Retrospective study of 177,631 consecutive mammograms double read during 1998-2003. SETTING: The Florence screening programme, involving 11 trained radiologists. Abnormalities reported by at least one reader prompted assessment. RESULTS: The referral rate was 2.89% for the first reader, 3.15% for the second reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were suspected only by the second reader (6.4% relative, 0.024% increase in absolute detection rate) and had a lower stage compared to the first reader (pTis-pT1b = 65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in 20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman examined, or 11,168 per additional cancer detected (versus 11,585 at a single reading). DISCUSSION: Second reading is effective in detecting a limited number of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and review findings (high rate of "screening errors" and BI-RADS R4b-c categories) suggest that second reading detects small "difficult cases" as well as larger cancers missed due to fatigue or loss of attention. Second reading reduces screening specificity to a minor extent, and since cancer detection at second reading seems cost-effective the procedure is recommendable in routine practice.

The role of arbitration of discordant reports at double reading of screening mammograms.

OBJECTIVE: To asses the effectiveness of arbitration of discordant double readings in mammography screening. DESIGN: A retrospective study of 1217 consecutive arbitrations. SETTING: A subset of discordant double readings from the Florence screening programme underwent arbitration by a third reader. RESULTS: Positive arbitration of 1217 discordant double readings prompted assessment in 476 cases (39.2%), detecting 30 cancers (6.3%). Of 741 negative arbitrations (60.8%), 311 have been followed up thus far, and two cancers (0.64%) occurred in the site previously suspected at one of the two independent readings. Arbitration had a sensitivity of 86.3% and a negative predictive value of 99.3%. Arbitration reduced the overall referral rates from 3.82% to 2.59% (relative decrease 32.1%). Due to false-negative arbitration, cancers detected per 1000 women screened would decrease from 4.58 to 4.50 (relative decrease 1.7%). For every cancer missed due to false-negative arbitration, 151 unnecessary recalls and 21,248 euro would have been saved, whereas the saved cost per screened woman due to arbitration was 1.72 euro. DISCUSSION: Arbitration of discordant double reading would substantially reduce referral rates with a limited reduction in cancer detection rate, and may be recommended as a routine procedure. Greater benefit from arbitration might be expected in the presence of high referral rates at independent double reading, a common scenario in a newly implemented service screening.

The effect of EUSOMA certification on quality of breast cancer care.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. RESULTS: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. CONCLUSION: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.

Assessment of the early impact of the population-based breast cancer screening programme in Florence (Italy) using mortality and surrogate measures.

The aim of this study was to evaluate the effects by the end of 1999 of the Florence breast screening programme that started in 1990. Approximately 60000 women (aged 50-69 years) were enrolled from 1990 to 1993. Breast cancer cases diagnosed from 1990 to 1996 were partitioned by the method of detection, classified by their tumour size and nodal status and followed-up for mortality at on the 31 December 1999. Incidence-based mortality in the 50-74-year-old women and advanced carcinomas rates were assessed. Due to low compliance (approximately 60%) and the long enrollment phase, only approximately 35% of the total age-specific population person-years were screened. The number of invasive cases diagnosed was 1122, 17% higher than the 958 expected. After the prevalence screening, a reduction of approximately a quarter in advanced carcinomas was observed in the invited women (Odds Ratio (OR): 0.74; 95% Confidence Interval (CI): 0.55-0.98). In the period 1990-1999, 547 breast cancer deaths were observed: 78 (14%) occurred in women invited and half of these in never responders, 385 (70%) occurred in cases diagnosed before screening started. Disproportionate numbers of deaths occurred in women with advanced tumours. The 19% mortality reduction for the invited women was of borderline statistical significance (observed/expected (O/E) deaths: 0.81; 95% CI: 0.64-1.01); by a one-sided test the result would be unequivocally significant. The mortality reduction attributable to screening in the whole population over the 10-year period was 3.2%. The incidence-based mortality analysis confirmed the current follow-up time is too short for screening to have had a major effect on the breast cancer mortality trends. Screening performance might be improved by a higher level of compliance and shorter interval times, but the estimate of the mortality reduction for the invited and the lower rate of advanced carcinomas confirmed that the effect of the programme is in the expected direction.

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.

Intraductal breast cancer: review of 183 consecutive cases.

The aim was to review a series of 183 intraductal breast cancer to define the diagnostic features and therapeutic outcome. Patients' average age was 54 years. Diagnostic procedures employed were clinical examination, mammography in 173 cases and fine-needle aspiration cytology in 98 cases. The sensitivity of clinical examination was 0.61, of mammography 0.74, of fine needle aspiration cytology 0.70. The sensitivity of clinical examination and mammography associated was 0.93. The surgical options adopted were: conservative surgery 80 cases, mastectomy 103 cases. Conservative surgery was followed by breast irradiation in 34 cases. Axillary dissection was performed in 122. 97 cases have been reviewed histologically. 60% of ductal carcinoma in situ (DCIS) were multifocal and 22% multicentric. Local recurrence, all infiltrating, occurred in the same breast after conservative surgery in 8 cases, 3 of which had received postoperative radiotherapy, and in 3 patients after mastectomy. Contralateral breast cancer was recorded in 13 cases, being synchronous in 4 (infiltrating in 3, DCIS in 1) and metachronous in 8 (all infiltrating). 3 patients died of breast cancer. The present series confirms the risk of ipsilateral cancer recurrence after conservative surgery but there are no significant differences relating to mammographic pattern, size, histological type, margin involvement and radiotherapy.

A model-based prediction of the impact on reduction in mortality by a breast cancer screening programme in the city of Florence, Italy.

The efficacy of breast cancer screening for women older than 50 years has been shown in several studies. Service screening is now ongoing or planned in several countries in Europe. MISCAN, a computer simulation programme, has been used to analyse data from the Florence District Programme (FDP) breast cancer experience. First, the model was fitted to the screening results for the period 1975-1986. A good correspondence between the model outcomes and the FDP results was achieved. It was then used to predict the impact on mortality of the new starting programme of the city of Florence (63,000 women, 50-69 years old). Assuming a 70% attendance rate, then for the city of Florence, 2563 screen-detected breast cancers are predicted for the period 1991-2020 out of the total number of 9095 breast cancers for all ages (28%). A total of 3720 deaths for breast cancer are expected without screening. An absolute reduction of 472 deaths (13%) is predicted for the whole population. The estimated number of years of life gained by screening until 2020 is 4354. Simulation by MISCAN has previously been a useful support tool for decision-making about screening. The present paper is the first based on a southern European experience. The possibility of applying MISCAN to predict the impact of a national programme in Italy is discussed.

Reproducibility of histological diagnosis of breast lesions: results of a panel in Italy.

Sixteen pathologists independently examined and classified a series of 81 breast lesions selected from the files of several Italian Pathology Departments in the context of a national task force on breast cancer (FONCAM). A four category classification system was used for analysis; according to the majority diagnosis (MD), simply defined as the most frequently reported in the panel, the series included 37 benign lesions without atypia (45.7%), nine atypical hyperplasias (11.1%), 18 in situ (22.2%) and 17 invasive carcinomas (21.0%). Concordance, estimated for all possible pair-wise comparisons between pathologists, was good (mean kappa value: 0.59). A comparison between the diagnoses of each pathologist and the panel majority diagnosis was also made. Overall, a global kappa value of 0.72 was found (range 0.57-0.85), with category-specific values being excellent for invasive carcinoma (0.89) and benign lesions without atypia (0.77), relatively good for in situ carcinoma (0.69) but poor for atypical hyperplasia (0.38). These results confirm that quality assurance procedures are particularly indicated for large screening programmes for breast cancer, and suggest that for atypical lesions strict diagnostic criteria should be adopted.

Patterns of axillary metastases in breast cancer.

Thirty-seven (4.1%) cases of nodal metastases skipping the first level are reported in a consecutive series of 912 breast cancer axillary dissections including 392 N+ cases. First level nodes examination is sufficiently accurate in assessing the quality of nodal status (negative or positive) but not the extent of nodal involvement (number of involved nodes).

Breast cancer early diagnosis experience in Florence: can a self referral policy achieve the results of service screening?

STUDY OBJECTIVE: To assess the impact of a breast clinic on a specific target population and evaluate early diagnosis performance indicators for breast cancer in the presence of a self referral policy. DESIGN: Women living in Florence between 1980 and 1989 who had undergone mammography at a self referral breast clinic were studied. Main outcome measures were the use of mammography in relation to age, symptoms, and the interval between two subsequent tests, and early diagnosis performance indicators were the detection rate (DR), the prevalence/incidence ratio, and the proportion of early detected cancers. Performance indicators were compared with those from formal screening programmes. SETTING: Florence, Italy. PATIENTS: All mammograms performed at the clinic from 1980-89 in 40-69 year old women living in Florence were examined (n = 42,226). Records included the date of birth and of the examination, the reason for testing (asymptomatic/presence of pain/presence of symptoms other than pain), and the TNM classification for breast cancer cases. MAIN RESULTS: The total number of mammograms performed per annum increased by 70% over the decade, but much of this was routine repeat mammography (54.1% in 1989). Rates of first examinations in asymptomatic women increased in the second half of the decade from 17 per 1000 in 1985 to 31 per 1000 in 1989. Mammographic coverage decreased with increasing age from 12.6% in 40-49 year olds to 6.0% in 60-69 years old. Performance indicators of the activity in asymptomatic women were comparable with those expected in service screening. The proportion of not advanced cancers detected in asymptomatic women was 62.3% with a DR of 5.3 per 1000, and the average prevalence/incidence ratio was 2.9. CONCLUSIONS: High quality mammography performed in a breast clinic in self referred asymptomatic women can achieve as good results as a formal invitation screening service. Only a few of these women will benefit, but those who do are likely to be younger (40-49 year old women).

Time interval since last test in a breast cancer screening programme: a case-control study in Italy.

STUDY OBJECTIVE: To evaluate a population based screening programme for breast cancer. DESIGN: This was a case-control study of women dying of breast cancer between 1977 and 1987 who had been invited to take part in a screening programme. SETTING: Community based study of women aged between 40 and 70 years (total population about 35,000 at 1981 census), living in 23 small towns near Florence, Italy. PARTICIPANTS: 103 cases were identified from death certification, and 515 living controls (five per case) selected for year of birth and town of residence. MEASUREMENTS AND MAIN RESULTS: Screening history was obtained from computer archive. Sociodemographic information was obtained from town registry offices and directly from relatives of the deceased and from the controls by postal questionnaire, and if necessary telephone or personal interview. Analysis was carried out on two age groups--40-49 years and 50+ years at diagnosis--and considered the number of screening tests and the time interval since the last test, separately and together. In the older age group, women with at least one screening test in the previous 2 1/2 years showed a 50% reduction in risk (odds ratio 0.49, 95% confidence interval [CI] 0.25-0.95). If they had also had another previous negative screen the risk was reduced to one third (odds ratio 0.35, 95% CI 0.14-0.85). There was a significant trend of decreasing risk with increasing number of screens in older women. No clear evidence of a similar protective effect was shown for women in the 40-49 year age group. CONCLUSIONS: A significant protective effect of the screening programme is evident in older women but not in younger ones. The data do not allow an assessment of optimal screening interval because of the small number of previously screened cases.

Proficiency test for screening mammography: results for 117 volunteer Italian radiologists.

OBJECTIVE: To analyse the performance of a large sample of Italian radiologists undergoing a proficiency test for screening mammography. DESIGN: Evaluation of performance indicators according to reference standards determined by a panel of experts (sensitivity (reference standard > or = 80%), recall rate (reference standard < or = 15%)). SETTING: 117 Italian radiologists of varying experience (years of practice 0.5-18, average 5.9; mammograms read 500-51,000, average 13,000), all currently reporting clinical mammography and planning to take part in screening in the near future. RESULTS: Eighty four of 117 (72%) radiologists reached the standard for sensitivity, 88 (75%) reached the standard for recall rate, and only 59 (50%) reached both standards and passed the proficiency test. The probability of passing the test was significantly correlated with mammographic practice (p = 0.015), mammograms read (p = 0.024), and mammograms read/year (p = 0.043). DISCUSSION: The performance of a large sample of Italian radiologists currently reporting clinical mammography was disappointing, indicating the need for proper training of at least 50% of the tested subjects. When implementing organised screening the health authority should set up a proper process for training and accrediting radiologists, and a proficiency test should be part of such a process.

The contribution of ultrasonography to the differential diagnosis of breast cancer.

Overall consecutive breast abnormalities (259 carcinomas, 1820 benign) examined with breast ultrasonography (US) are reported. US sensitivity, specificity and positive predictive value were 67.6, 97.7 and 81.0%, resp. (the corresponding values were 57.9, 97.9 and 77.2% for palpation, 79.9, 93.5 and 73.7% for mammography, and 97.6, 92.6 and 87.6% for cytology). US sensitivity was unaffected by age, whereas it was strongly influenced by tumor size (pT1-76.1%; pT2-87.1%) and histologic type (intraductal-7.4%; invasive ductal/lobular-83.4%; invasive special types-64.1%). The features of the lesions at US were significantly associated with cancer (irregular margins, posterior acoustic shadowing) or benign lesions (anechoic structure, lateral shadowing, posterior acoustic enhancement) but had a limited diagnostic accuracy. Overall, US visualized 174 (benign-24, suspicious-150) of 188 palpable, and 32 (benign-7, suspicious-25) of 71 nonpalpable cancers. US contribution was determinant to final diagnosis in 4 of 7 cancers, missed at palpation and mammography, but was at least partially responsible for 8 unnecessary biopsies of benign lesions. A negative/benign US report contributed to avoid unnecessary biopsy in 71 suspicious cases at palpation/mammography. Routine US examination of clinical/mammographic abnormalities is recommended for the advantages of US-guided aspiration and to reduce the frequency of unnecessary biopsies.

Causes of breast cancer misdiagnosis at physical examination.

2740 consecutive breast cancers undergoing physical examination were reviewed. Ninety-two subclinical cancers detected at mammography were excluded from further evaluation and the study focused on palpable false benign cancers. The sensitivity of physical examination varied according to T category (TIS = 0.48, T1 = 0.70, T2 = 0.90, T3 = 0.89, T4 = 0.93), age (20-29 = 0.77, 30-39 = 0.58, 40-49 = 0.75, 50-59 = 0.84, 60-69 = 0.90, greater than 69 = 0.94) and operator (range 0.69-0.89), a significant difference being recorded in favor of more expert operators. Multivariate analysis (Cox) showed that T category, patient's age and operator experience are independent determinants of sensitivity. This study confirms that physical examination is not very sensitive, particularly for small tumors and in younger women and should always be performed by expert operators.

The diagnostic efficacy of mammography and palpation in early detection of breast cancer.

The diagnostic efficacy of mammography and physical examination, separately and considered together, are evaluated in 912 cases of breast cancer detected at the Center for Social Diseases of the Florence District, where there is a mass-screening program (110 cases) and a diagnostic service for self-referred women (810 cases). The overall sensitivity of the 2 methods increases with age; the trends of diagnostic efficacies of mammography and palpation according to age are similar, except in the 40-44 year age group, in which physical examination has a lower percentage of false-negative cases. In the screening group, there is a greater proportion of nonpalpable cancers and mammography has a larger diagnostic efficacy except in the 40-44 year age group. These results agree with the better sensitivity of mammography in smaller lesion (TI) and with the larger proportion of noninterpretable mammographies in younger women, because of the density of mammalian glands.

Reasons for failure of physical examination in breast cancer detection (analysis of 232 false-negative cases).

The diagnostic role of physical examination (PE) is evaluated in 1450 cases of breast cancer detected in 34,677 women controlled at the Centro per lo Studio e la Prevenzione Oncologica in the period 1974-1981. In 47 cancer cases, PE findings were normal since the neoplasm was not clinically palpable because of its size and site, and in another 185 cases the clinical diagnosis was benignancy without evidence of suspect signs. Therefore, the overall sensitivity of PE was 84%. PE errors did not involve a therapeutic delay for the patient in 75% of cases in which a biopsy was recommended for clinical benignancy or for suspicion on the basis of other diagnostic methods. The present study confirms that PE has a good diagnostic sensitivity when the examined population is represented by self-referred women, who for the most part are symptomatic, whereas it cannot be considered as the only diagnostic test for early diagnosis in mass screening, since in asymptomatic women a large number of cancers are not clinically palpable. Moreover, PE shows lower sensitivity for small lesions and in younger women. Extensive use of fine needle aspiration cytology and other diagnostic methods in association with PE is therefore recommended to reduce the possibility of errors.