Search

Background & Objectives: Three-dimensional (3D)-mammography (tomosynthesis) may improve breast cancer detection. We examined centre-specific effect of integrated 2D/3D mammography based on the STORM (screening with tomosynthesis or standard mammography) trial., Methods: Asymptomatic women who attended population-based screening through Trento and Verona screening centres were recruited into STORM, a prospective comparison of screen-reading in two sequential phases: 2D-mammography only and integrated 2D/3D mammography. Outcomes were the number and rates of detected cancers and of false positive recalls (FPR), and incremental cancer detection rate (CDR). Paired binary data were compared using Mc Nemar's test., Results: Of 33 cancers detected in Trento, 21 were detected at both 2D and 2D/3D screening, 12 cancers were detected only with integrated 2D/3D screening compared with none detected at 2D-only screening (P < 0.001). Of the 26 cancers detected in Verona, 18 were detected at both 2D and 2D/3D screening, 8 cancers were detected only with integrated 2D/3D screening compared with none detected at 2D-only screening (P = 0.008). There were no differences between centres in baseline CDR, and incremental CDR attributable to 3D-mammography was similar for Trento (2.8/1000 screens) and for Verona (2.6/1000 screens). Trento had 239 FPR (5.7% of screens): 103 FPR at both screen-readings, 93 FPR only at 2D-mammography compared with 43 FPR only at 2D/3D-mammography (p < 0.001). Verona had 156 FPR (5.2% of screens): 78 FPR at both screen-readings, 48 FPR only at 2D-mammography compared with 30 FPR only at 2D/3D-mammography (p = 0.054). Estimated reduction in FPR proportion had recall been conditional to 2D/3D-mammography-positivity differed between centres (21.0% versus 11.5%; P = 0.02)., Conclusion: Integrated 2D/3D-mammography significantly increased cancer detection for both screening services; potential reduction in FPR is likely to differ between centres with those experiencing relatively higher FPR most likely to benefit from 2D/3D-mammography screening., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate increment cancer detection rate generated by ultrasound (US)., Materials and Methods: US only detected cancers were assessed for 22,131 self-referring asymptomatic women with negative mammography and subgroups by age, previous cancer, breast density. Invasive assessment and surgical biopsy rate were evaluated., Results: The overall US detection was 1.85 per thousand (41/22,131). In the subgroups it was: 1.95 per thousand (22/11,274) in women <50 years vs 1.75 per thousand (19/10,857) in women ≥ 50 years (p = 0.42), 5.49 per thousand (12/2183) in women with previous cancer vs 1.45 per thousand (29/19,948) in women without cancer history (p = 0.0004), 2.21 per thousand (22/9960) in dense breasts (p = 0.17) vs 1.56 per thousand (19/12,171) in fatty breasts. The US generated invasive assessment was 1.9% (422/22,131). The benign to malignant open surgical biopsy ratio was 0.17 (7/41)., Conclusion: Adding US to negative mammography allowed for substantial incremental cancer detection rate (1.85 per thousand), particularly at age <50 years, in women with previous breast cancer and in dense breasts., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: Core needle biopsy (CNB) has progressively replaced fine needle aspiration cytology (FNAC) in the diagnosis of breast lesions. Less information is available on how these tests perform for biopsy of ultrasound (US) visible breast lesions. This study examines the outcomes of CNB and FNAC in a large series ascertained with surgical histology or clinical-imaging follow-up., Materials and Methods: Retrospective five-year audit of 3233 consecutive US-guided needle samplings of solid breast lesions, from self-referred symptomatic or asymptomatic subjects, performed by six radiologists in the same time-frame (2003-2006): 1950 FNAC and 1283 CNB. The probability of undergoing CNB as a first test instead of FNAC was evaluated using logistic regression. Accuracy and inadequacy were calculated for each of CNB and FNAC performed as first test. Accuracy measures included equivocal or borderline/atypical lesions as positive results., Results: The probability of CNB as a first test instead of FNAC increased significantly over time, when there was a pre-test higher level of suspicion, in younger (relative to older) women, with increasing lesion size on imaging, and for palpable (relative to impalpable) lesions. Inadequacy rate was lower for CNB (B1 = 6.9%) than for FNAC (C1 = 17.7%), p < 0.001, and specifically in malignant lesions (B1 = 0.9% vs. C1 = 4.5%; p < 0.001). False negative rate was equally low for both CNB and FNAC (1.7% each test). CNB performed significantly better than FNAC for absolute sensitivity (93.1% vs. 74.4%; p < 0.001) and complete sensitivity (97.4% vs. 93.8%; p = 0.001), however specificity was lower for CNB than FNAC (88.3% vs. 96.4%; p < 0.001). Absolute diagnostic accuracy was higher for CNB than FNAC (84.5% vs. 71.9; p < 0.001) while FNAC performed better than CNB for complete diagnostic accuracy (95.4% vs. 93.2; p < 0.008). In the small subgroup assessed with CNB after an inconclusive initial FNAC (231 cases) there was improved complete sensitivity (from 93.8% to 97.0%) however this also increased costs., Conclusion: FNAC and CNB were generally performed in different patients, thus our study reported indirect comparisons of these tests. Although FNAC performed well (except for relatively high inadequacy), CNB had significantly better performance based on measures of sensitivity, but this was associated with lower specificity for CNB relative to FNAC. Overall, CNB is the more reliable biopsy method for sonographically-visible lesions; where FNAC is used as the first-line test, inadequate or inconclusive FNAC can be largely resolved by using repeat sampling with CNB., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Breast radiological density is a determinant of breast cancer risk and of mammography sensitivity and may be used to personalize screening approach. We first analyzed the reproducibility of visual density assessment by eleven experienced radiologists classifying a set of 418 digital mammograms: reproducibility was satisfactory on a four (BI-RADS D1-2-3-4: weighted kappa = 0.694-0.844) and on a two grade (D1-2 vs D3-4: kappa = 0.620-0.851), but subjects classified as with dense breast would range between 25.1 and 50.5% depending on the classifying reader. Breast density was then assessed by computer using the QUANTRA software which provided systematically lower density percentage values as compared to visual classification. In order to predict visual classification results in discriminating dense and non-dense breast subjects on a two grade scale (D3-4 vs, D1-2) the best fitting cut off value observed for QUANTRA was ≤22.0%, which correctly predicted 88.6% of D1-2, 89.8% of D3-4, and 89.0% of total cases. Computer assessed breast density is absolutely reproducible, and thus to be preferred to visual classification. Thus far few studies have addressed the issue of adjusting computer assessed density to reproduce visual classification, and more similar comparative studies are needed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Ongoing debate regarding the value of pre-operative MRI in staging patients with newly diagnosed breast cancer has resulted from the lack of evidence on its clinical efficacy, which contrasts MRIs capability for detecting additional disease (occult on conventional imaging) in the cancerous breast. We undertook a validation study of EUSOMA criteria that recommend selection of breast conserving surgery (BCS) candidates to pre-operative MRI. We examined whether these criteria were associated with a differential likelihood of a recommendation for mastectomy. In a cohort of 200 subjects, recommended for BCS following mammography (M) and ultrasound (US), and who also subsequently had pre-operative MRI, the proportions recommended for mastectomy based on MRI, where the criterion was present versus absent were: invasive lobular cancer (17.9% versus 17.4%; p=0.87); high familial risk (14.7% versus 18.1%; p=0.82); M/US tumour size discrepancy >1cm (32.1% versus 15.1%; p=0.05); and for any of these criteria versus none (21.6% versus 14.3%; p=0.24). These findings suggest that EUSOMA criteria for selection to pre-operative MRI may be inefficient as they do not appear to differentiate those at risk of having more extensive disease and likely to receive a mastectomy recommendation, with the exception of M/US tumour size discrepancy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We review the accuracy and potential effect of mammography in surveillance of women with a personal history of breast cancer (PHBC). A literature review was performed to identify studies on screening mammography or breast surveillance reporting data on the accuracy or detection capability of mammography, or the effect of early detection of second breast cancers, in women with a PHBC. Evidence on mammography screening in women with PHBC comes from non-randomised studies, and is generally limited by several factors including design limitations. The proportion of ipsilateral breast recurrences detected with mammography ranges between 50% and 80% (including cancers detected also on clinical examination) but is lower at 8%-51% for mammography-only detection. Mammography detects approximately 45%-90% of contralateral cancers. There is evidence of a potential benefit for asymptomatic/early-detected second breast cancers (range of estimated hazard ratios: 0.10-0.86) relative to symptomatic or clinical-detection, in various surveillance strategies that include mammography, however these estimates are likely to have overestimated screening benefit. New evaluations of screening women with a PHBC are needed from screening programs or population datasets, to provide comprehensive measures of screening accuracy and outcomes in this population of women., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: The impact of early detection of second breast cancers in women who have survived a primary breast cancer is unknown. We examined the prognostic effect of detection of ipsilateral breast relapse (IBR) or contralateral breast cancer (CBC) in the asymptomatic relative to symptomatic phase., Patients and Methods: Subjects were women with histology-verified second (invasive or in situ) breast cancer (N = 1044) in a breast centre in Florence (1980-2005). Symptom status, test, tumour stage, and outcomes data were obtained from clinical records and linkage with mortality registry. Disease-specific survival was measured from first cancer diagnosis to avoid lead-time bias. Sensitivity analysis was used to allow for length-time bias., Results: Second cancers (IBR = 455; CBC = 589; median age 60 years) were diagnosed in 699 asymptomatic and 345 symptomatic women (67% versus 3%, P < 0.0001). Mammography was more sensitive than clinical examination (86% versus 57%, P < 0.0001); however, 13.8% of cases were only identified clinically. Asymptomatic cancers were smaller than symptomatic for both IBR (P < 0.001) and CBC (P < 0.001). Early-stage tumours were more frequent in asymptomatic (58.1%) than symptomatic (22.6%) women (P < 0.0001). Fewer women with asymptomatic than symptomatic CBC had node metastases (P = 0.0001). Hazard ratio (HR) for asymptomatic (relative to symptomatic) detection was 0.51 (0.32-0.80) for IBR, 0.53 (0.36-0.78) for CBC, and 0.53 (0.40-0.72) in all subjects (P < 0.0001). Length bias-adjusted HRs ranged from 0.53 to 0.73., Conclusion: Detection of second breast cancers in the asymptomatic phase leads to detection of early-stage cancer and improves relative survival by between 27% and 47%.

Surveillance of interval cancers (IC) lacks standardisation of review methodologies. We investigated the extent to which 'informed' or 'blinded' review may affect IC classification. This is a retrospective study of 100 validated screening mammograms (20 IC, 80 negative screens) independently reviewed by six radiologists. Three sequenced review methods with increasing information were used: (1) blinded (no IC information, case mix), (2) partially informed, and (3) fully informed. IC 'screening error' (SE) reports averaged 24% (10-40), 33% (20-55), and 42% (35-50) for phases 1, 2, and 3, while 'minimal signs' (MS) reports averaged 6% (5-15), 10% (10-20), and 20% (15-30), respectively. Negative mammograms classification was MS in 18% (7-39) or SE in 19% (11-29), respectively. MS or SE classification was more likely for method 2 (OR=1.78, p=0.033) and method 3 (OR=3.91, p=0.000) relative to method 1, but no reader effect was evident. Inter-observer agreement in classifying at method 1 was slight (k 0.20), lowest (k 0.06) for MS, and fair (k 0.25) for negative and SE categories. More 'informed' review is more likely to yield an IC classification as MS or SE. Due to expected variability, review methods need standardisation to improve screening quality. Our data support blinded review of IC in mammography screening.

Combining mammography and ultrasound improves the sensitivity of imaging diagnosis. In the context of clinical masses, where percutaneous needle biopsy is routinely incorporated into the diagnostic pathway, little is known about the incremental gain in sensitivity where using single relative to combined imaging. We examined the sensitivity of imaging and needle biopsy combinations in a cohort of 1000 women with clinically evident (clinically presenting and/or clinically palpable) breast cancer. We report the distribution of age, tumour stage and node status, clinical findings, and individual test outcomes in all subjects. Sensitivity--true positive rate for cancer detection--of different test combinations (with the number of cases missed in 1000 subjects given in parentheses) is: mammography and ultrasound 97.9% (21); mammography with needle biopsy 99.5% (5); ultrasound with needle biopsy 99.5% (5); combined imaging with needle biopsy 99.6% (4). Using only one imaging test (irrespective of whether that is mammography or ultrasound) in combination with needle biopsy provides the same sensitivity, with an incremental gain in sensitivity of 0.1% where combined imaging is included into the diagnostic pathway. This is largely due to needle biopsy identifying most cancers missed on single imaging thus negating the effect of additional imaging on overall sensitivity.

Background: Gastric cancer may be suspected with otherwise unexplained positive faecal occult blood testing., Aims: To assess the frequency of gastric cancer following positive faecal occult blood testing and negative colonoscopy., Subjects: Age 40-74 cohort at first screening (1985-2001) with (a) faecal occult blood testing- (83,489), (b) faecal occult blood testing +/colonoscopy+ (2025), or faecal occult blood testing+/colonoscopy- (3555)., Methods: Gastric cancer incidence in faecal occult blood testing subsets, compared with expected standardized incidence rates., Results: Gastric cancer risk was increased (standardized incidence rate=146.7; 95% confidence interval: 105.8-203.4) in faecal occult blood testing+/colonoscopy- subjects. A four-fold excess incidence occurred during first year (observed cases=10, standardized incidence rate=408.3; 95% confidence interval: 219.7-758.8), irrespective of faecal occult blood testing type (guaiac, immunological). No excess risk occurred in faecal occult blood testing- (observed cases=53, standardized incidence rate=91.2; 95% confidence interval: 84.1-98.8) or in faecal occult blood testing+/colonoscopy+ subjects (observed cases=2, standardized incidence rate=101.9; 95% confidence interval: 25.5-407.4). Assuming a 100% 3-year study sensitivity for gastric cancer, faecal occult blood testing positive predictive value would be 0.4% (40-74 years) or 0.7% (> or =60 years) in faecal occult blood testing+/colonoscopy- subjects., Conclusions: Data suggest an association of faecal occult blood testing+/colonoscopy- and excess gastric cancer incidence in the following year. Due to low faecal occult blood testing+ positive predictive value, routine upper digestive tract endoscopy in these subjects is questionable.

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.

The inter- and intraobserver agreement (K statistic) in reporting according to BI-RADS assessment categories was tested on 12 dedicated breast radiologists, with little prior working knowledge of BI-RADS, reading a set of 50 lesions (29 malignant, 21 benign). Intraobserver agreement (four categories: R2, R3, R4, R5) was fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80) or almost perfect (>0.80) for one, two, five or four radiologists, or (six categories: R2, R3, R4a, R4b, R4c, R5) fair, moderate, substantial or almost perfect for three, three, three or three radiologists, respectively. Interobserver agreement (four categories) was fair, moderate or substantial for three, six, or three radiologists, or (six categories) slight, fair or moderate for one, six, or five radiologists. Major disagreement occurred for intermediate categories (R3=0.12, R4=0.25, R4a=0.08, R4b=0.07, R4c=0.10). We found insufficient intra- and interobserver consistency of breast radiologists in reporting BI-RADS assessment categories. Although training may improve these results, simpler alternative reporting methods (systems), focused on clinical decision-making, should be explored.

The inter- and intraobserver agreement (kappa-statistic) in reporting according to Breast Imaging Reporting and Data System (BI-RADS((R))) breast density categories was tested in 12 dedicated breast radiologists reading a digitized set of 100 two-view mammograms. Average intraobserver agreement was substantial (kappa=0.71, range 0.32-0.88) on a four-grade scale (D1/D2/D3/D4) and almost perfect (kappa=0.81, range 0.62-1.00) on a two-grade scale (D1-2/D3-4). Average interobserver agreement was moderate (kappa=0.54, range 0.02-0.77) on a four-grade scale and substantial (kappa=0.71, range 0.31-0.88) on a two-grade scale. Major disagreement was found for intermediate categories (D2=0.25, D3=0.28). Categorization of breast density according to BI-RADS is feasible and consistency is good within readers and reasonable between readers. Interobserver inconsistency does occur, and checking the adoption of proper criteria through a proficiency test and appropriate training might be useful. As inconsistency is probably due to erroneous perception of classification criteria, standard sets of reference images should be made available for training.

Incidence rates of adenocarcinoma of the uterine cervix have been reported to be increasing in several countries, but not in Italy. The aim of the present study was to analyse trends in cervical cancer incidence by histological type in two districts of Central Italy (Florence and Prato), covered by the Tuscany Cancer Registry (RTT), where cytological screening had been available since the 1970s. Incident cervical cancers during 1985-2000 were 1012. Estimated Annual Percent Change (EAPC) by age-groups and histological type were computed. Incidence increased for adenocarcinoma (EAPC = +5.7%; 95% confidence interval (CI)+2.8; +8.6); whereas, it decreased for squamous cancer (EAPC = -1.9%; 95% CI-3.8; 0) and for other or not specified types (EAPC = -4.4%; 95% CI-10.0; +1.5). Adenocarcinoma increased significantly among younger women (<55 years) but not among older ones, whereas squamous cell cancer decreased among older women only. The burden of cervical cancers might increase in the future if no specific preventive strategies for adenocarcinoma are implemented.

The aim of the present study was to monitor the occurrence of interval (breast) cancers (IC) as an interim outcome measure of quality assurance in the mammographic screening programme of the District of Florence. IC were identified by linking breast screening data with registrations of breast cancers from the Tuscany Tumour Registry. The main outcome measures were the numbers, rates, and the proportionate incidence of IC. Overall, 90 invasive IC were observed among women who attended the breast screening programme in the District of Florence from 1 January 1985 to 31 December 1993, respectively, 23, 50, on 17 cases, at 1, 2, and 3 years after the last negative screening test. Expressed as a proportion of underlying incidence, the figures are 16, 44, and 46%. As to risk factors for IC, mammographic density was the most important one in the present survey, whereas no effect of age emerges from the present study.

Despite its importance for clinical policy, there is little research on the age at which ultrasound or mammography is the preferred initial diagnostic test in women with breast symptoms. We analysed data from a series of 3799 consecutively presenting cancers. The overall sensitivity was 77.6% for mammography and 80.5% for ultrasound. Sensitivity increased with age in both mammography and ultrasound, though more steeply for mammography. In the 975 women who had both tests, ultrasound had a higher sensitivity than mammography in women younger than 62 years of age, whereas mammography had a higher sensitivity than ultrasound in women older than 62 years. However, if the test results of the 2393 women who had mammography only are compared with the ultrasound results of the 975 women who had both tests, the 'cross-over' age at which the sensitivity of the two tests is equal occurs at the earlier age of 48 years. The presence of a palpable finding increases the sensitivity of ultrasound but does not influence the sensitivity of mammography.

Two consecutive series of 107 invasive carcinomas and 108 carcinomas in situ of the breast were considered retrospectively. The main symptomatic, clinical and cytological features were retrieved from clinical records, whereas the features at mammography and/or ultrasonography were reclassified at a blinded review by an expert radiologist. The power of predicting invasion on the basis of these features was then evaluated. The accuracy of such a prediction was compared to that of a mathematical model using the same diagnostic features by multivariate logistic regression analysis. Neither approach reached a satisfactory accuracy, but the radiologist's judgment (sensitivity 97.1%, specificity 81.9%, positive predictive value 98.4%, negative predictive value 71.6%, overall accuracy 95.8%) was slightly superior to the mathematical model (sensitivity 93.2%, specificity 87.9% positive predictive value 98.8%, negative predictive value 53.7%, overall accuracy 92.8%). Although some presentations are significantly associated with invasive or in situ status, diagnostic features alone are not sufficiently accurate to bypass histological confirmation, although they might give useful clinical indications.

The role of breast scintigraphy in the evaluation of 30 women with an uncertain diagnosis following triple assessment was investigated. Scintigraphy was positive in 7 of 13 cancers and 3 of 17 benign lesions and dubious in 1 of 13 cancers and 2 of 17 benign lesions. Sensitivity ranged from 61.5% to 53.8% depending whether dubious lesions were designated as positive or negative. This study shows that breast scintigraphy is not sufficiently sensitive or specific to use in the evaluation of lesions of uncertain diagnosis following triple assessment.

Objectives: To estimate overdiagnosis (detection of latent carcinomas) as a consequence of screening for prostate cancer., Design: Based on actual screen (first or repeat) detected and interval prostate cancer rates observed in the Florence screening pilot study, a scenario was simulated where males aged 60 years (or 65) had six biennal screens and were followed up for four years. Overdiagnosis was determined as the proportional excess of cancers detected by screening with respect to that expected in its absence., Setting: City of Florence, Italy, from 1992 through 1995., Population: 2,740 resident males, aged 60 to 74 years., Results: Overdiagnosis was estimated to be 51% (95% confidence limits: 44%-55%) or 93% (85%-101%) for age 60 or 65 at entry. Comparison with other screening experiences obtaining higher detection rates suggests that a more aggressive screening approach could be associated with overdiagnosis estimates as big as 200%-250%., Conclusions: Screening for prostate cancer is associated with a relevant risk of overdioagnosis. As latent carcinomas can not be presently identified, this would lead to overtreatment in most overdiagnosed cases. The negative consequences of overdiagnosis (knowledge of having a cancer) and of overtreatment (impotence, incontinence, perioperatory death) may be extremely serious. In absence of any scientific evidence of screening benefits (if any) screening should not be recommended as a current practice, but should be limited to prospective controlled studies designed to assess its cost-effectiveness.

Background: The widespread belief that fibroadenoma is associated with an increased risk of subsequent breast cancer is based on studies of histologically-confirmed fibroadenomas. In current practice only a minority of fibroadenomas are excised; most of them are diagnosed on the basis of palpation and imaging, and are not surgically removed. The decision for surgical excision may be influenced by the presence of individual risk factors, and this can act as a confounder and bias studies that are based only on surgically excised fibroadenomas., Patients and Methods: To investigate this hypothesis we linked data from a consecutive series of 3938 fibroadenomas diagnosed histologically (n = 1335) or clinically (n = 2603) in women aged 30 to 69 years to the Tuscany Cancer Registry database. After exclusion of concurrent breast cancers or cancers occurring within six months after the diagnosis of fibroadenoma, the observed and expected incidence of subsequent breast cancer were compared., Results: The overall Standardized Incidence Ratio (SIR) for excised and non-excised fibroadenomas was 1.38 (95% CI = 1.1-1.7). The SIR for histologically-confirmed fibroadenomas was 2.0 (95% CI 1.4-2.7) whereas there was no apparent risk for non-excised fibroadenomas (SIR = 0.97, 95% CI = 0.7-1.4)., Conclusion: This study suggests that assessment of breast cancer risk subsequent to a diagnosis of fibroadenoma may be biased if the analysis is limited to surgically-excised fibroadenomas.

Background: Early detection of locoregional recurrences of breast cancer is possible with a variety of diagnostic methods. A combination of palpation, sonography and aspiration cytology is probably as accurate and certainly simpler, faster and cheaper compared to other more complicated and costly tests (computerized tomography, magnetic resonance imaging, lymphoscintigraphy). Retrospective studies have estimated that periodic observation may anticipate the detection of local symptomatic recurrences of about 3 months time with respect to their symptomatic onset. After correcting for lead time, this anticipated diagnosis has a moderate to null effect on prognosis (survival from primary treatment) in retrospective studies. According to their natural history, most local recurrences are just a local presentation of diffuse metastatization and, except for a few subgroups (isolated recurrent nodules in the mastectomy scar, isolated axillary nodes), prolonged disease-free survival suggests the absence of associated progressing systemic disease., Conclusions: Periodic control aimed at the early detection of these local recurrences might be recommended, although the prognostic impact (if any) of such a policy is probably limited, and extremely large controlled studies would be necessary to demonstrate impact at a significant level.

Background: A preliminary inquiry into the follow-up practices of Italian breast cancer centers revealed a considerable diversity of policy. It is clear that accurate follow-up examinations supply important information about the development of metastases, but there is no clinical proof that they extend survival time. It is possible that the effects of early diagnosis are only negative, extending the period over which the patient is aware of her illness and leading to over-diagnosis, overtreatment and increased health-care costs., Patients and Methods: In a study involving the national oncological centers, patients were randomized into two groups: an intensive follow-up group (6 monthly chest X-rays and bone scans) and a control group (clinical examination only)., Results: An excess of isolated bone and intrathoracic metastases were observed in the intensive follow-up group. The survival curves showed no difference between the two groups., Conclusions: Six monthly X-rays and bone scans provide occasion for early diagnosis of intrathoracic and bone metastases without, however, influencing overall 5-year survival. Recourse to diagnostic tests only in the presence of symptoms appears to be the most appropriate follow-up procedure. However, other studies considering long term effects of early diagnosis and the effects of considering long term effects of early diagnosis and the effects of new diagnostic tests and/or treatment modalities are clearly needed.

A series of 59 phyllodes tumors of the breast was retrospectively reviewed (average follow-up = 3.9 years). Clinical features (age, size of tumor) and diagnostic tests (palpation, mammography, sonography and cytology) were found to be inaccurate in predicting benign (n = 22), borderline (n = 12) or malignant (n = 25) histological type. Limited surgery was associated with a relatively high proportion of local recurrence (enucleation/enucleoresection = 3/5, wide resection = 12/30) compared with mastectomy (2/24). No significant association was observed between the probability of local recurrence and patient's age, histological type or lesion size. Although the study confirms that limited surgery may cure phyllodes tumor, careful follow-up of all patients is needed, since no reliable risk factors for recurrence are available. In malignant cases, axillary node involvement was nil and distant metastases were infrequently observed (3/25). Axillary dissection and search for asymptomatic metastases is not recommended.

We report on 156 consecutive cases of in situ ductal carcinoma (DCIS) of the breast observed from 1968 to 1988. The relative frequency of DCIS was much higher in screened, with respect to self-referred, women and a significant association of DCIS with younger age was observed. The combined use of mammography and physical examination identified 138 of 156 total DCIS cases as suspicious. Mammography, physical examination or cytology (of nipple discharge or needle aspirate) were the only tests to provide suspicious evidence in 35, 22 and four cases respectively. DCIS was a relatively unexpected surgical finding in 13 apparently benign cases. Different surgical options were recorded in the study period but a temporal trend in favour of conservative surgery was evident. Subsequent ipsilateral or contralateral breast cancer was recorded in seven and six cases respectively. Death from breast cancer occurred in five cases, all of whom had contralateral or subsequent ipsilateral infiltrating cancer. This figure confirms the high curability of DCIS if local control is achieved.

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.

We report on the possible diagnostic and prognostic role of circulating immune complexes (CIC) determination in breast cancer. A sensitivity of 87% and a specificity of 90% were observed in a case-control study of 15 cancers and 25 noncancer healthy controls. A direct correlation of CIC level to the presence and probably to the entity of the tumor mass was assessed by comparing preoperative to postoperative CIC determinations in cancer cases: CIC levels were significantly lower after tumor removal. These preliminary results suggest further studies on the use of CIC determination in the follow-up of breast cancer for the early diagnosis of recurrent disease.