US correlation for MRI-detected breast lesions in women with familial risk of breast cancer.

AIM: To examine the value of US correlation for MRI-detected breast lesions in women with familial risk of breast cancer. METHODS: From an initial dataset of 245 women with positive family history who had breast cancer surveillance involving mammography or MRI between November 1994 and February 2001, 179 subjects with follow-up data were selected. A total of 43 women with 48 MRI-detected lesions underwent further assessment with US. Histopathological correlation was available from 38 breast biopsies performed for 33 women. RESULTS: Sonographic correlates were identified in 32 (66.7%) of the 48 MRI-detected lesions, with cancer present in 11 (34.4%) of these. This compares with 1 (6.3%) cancer found in the 16 lesions without sonographic correlates. Of the 12 malignant lesions, 11 (91.7%) had sonographic correlates whereas 21 (58.3%) of the 36 benign lesions had sonographic correlates. In all 74% of breast biopsies were performed under US guidance compared with 8% under MRI guidance. The proportion of MRI- and US-correlated benign and malignant lesions undergoing US-guided biopsy were 85.7% and 90.9%, respectively. CONCLUSION: The probability of cancer was significantly higher in MRI-detected breast lesions with sonographic correlates compared with those without such correlation. The advantage of convenient biopsy under US guidance as opposed to MRI guidance highlights the value of sonographic assessment of MRI-detected breast lesions.

Breast ultrasound in women with familial risk of breast cancer.

INTRODUCTION: The aim of this study was to assess the performance and value of breast ultrasound in women with familial risk of breast cancer. MATERIALS AND METHODS: From an initial dataset of 245 women with positive family history who had breast cancer surveillance utilising mammography or magnetic resonance imaging (MRI) between November 1994 and February 2001, 179 subjects with follow-up data were selected. Eighty-four women had breast ultrasound done with histopathological correlation available from 48 breast biopsies performed in 42 women. RESULTS: The sensitivity of ultrasound, mammography and MRI was 83.3%, 53.9% and 93.3%, respectively. The specificity of ultrasound, mammography and MRI was 65.5%, 85.7% and 63.6%, respectively. Ultrasound was the imaging modality with intermediate sensitivity, specificity, negative predictive value (NPV) and cancer detection rate. The sensitivity, specificity, positive predictive value (PPV), NPV and accuracy of combined mammography and ultrasound were 92.9%, 62.5%, 52.0%, 95.2% and 71.7%, respectively. These results did not differ significantly from MRI. Almost two-thirds of the breast biopsies were performed under ultrasound guidance. CONCLUSIONS: Although breast ultrasound screening per se was not assessed in this study, extrapolation of these results to sonographic screening of high familial risk women would come at a better specificity to MRI, albeit with a 10% decrease in sensitivity but at a fraction of the cost of MRI. Ultrasound also provides the advantage of convenient imaging guidance for biopsy. Employing ultrasound following mammography would match MRI in sensitivity, specificity, PPV, NPV and accuracy, and should not be ignored in these women.

The significance of circumscribed malignant mammographic masses in the surveillance of BRCA 1/2 gene mutation carriers.

Breast cancers in gene mutation carriers may escape mammographic detection because of rapid growth and tumor expansion. Therefore, they may mimic benign lesions on the mammogram. Twenty-nine BRCA 1/2 mutation carriers under surveillance developed 31 breast cancers between 1994 and 2001 at a mean age of 44.2 years. Controls were 63 women with 67 breast cancers in the same period at a mean age of 53.8 years, also under surveillance because of a life time risk of at least 15%. In 26% of the carriers vs. 48% of the controls, mammography was the method that first suspected a malignancy. Seven radiologists performed a retrospective review of the original mammograms to establish technical assessment, with special attention for circumscribed lesions and estimated probability of malignancy. In the mutation carriers seven (23%) circumscribed non-calcified mammographic masses were found and three in the controls (4.5%) P=0.01. These masses were proven to be malignant. In both groups around 70% of these fast-growing circumscribed lesions were detected by the patients. The masses were situated in breasts with a good interpretable breast pattern. BRCA 1/2 mutation carriers had a significantly higher percentage of circumscribed non-calcified mammographic masses that proved to be malignant. These mammographic lesions in women at high risk should be described as at least Birads 0 and worked-up with ultrasound and needle biopsy.

Reproducibility of mammographic classifications for non-palpable suspect lesions with microcalcifications.

Observer variability in interpretation of mammograms is a well-known problem, especially for microcalcifications. The classification of the mammographic findings depends upon this interpretation. We performed an intraobserver study to evaluate a breast imaging reporting and data system (BI-RADS) based method for description and classification of non-palpable lesions with microcalcifications. A set of 100 non-palpable mammographic lesions mainly consisting of microcalcifications was described and classified on two occasions, by two radiologists at an interval of 6 months. The intraobserver variability was evaluated with kappa statistics. The overall agreement for the classification was moderate (kappa 0.54). The lowest kappa values were observed for the categories "probably benign (BI-RADS 3, kappa 0.59)" and "suspicious abnormality (BI-RADS 4, kappa 0.44)". The clinical management (follow-up or biopsy) of non-palpable lesions consisting of microcalcifications depending upon radiological classification in the groups BI-RADS 3 (follow-up) and BI-RADS 4 (biopsy) is therefore debatable.

Diagnostic accuracy for different strategies of image-guided breast intervention in cases of nonpalpable breast lesions.

To find out whether ultrasound-guided fine-needle aspiration (FNA) and ultrasound and stereotactic-guided large core needle biopsy (LCNB) are reliable alternatives to needle-localised open breast biopsy (NLBB) in daily practice, we performed a retrospective study and evaluated the validity of these methods. In all, 718 women with 749 nonpalpable breast lesions from three Dutch Hospitals were included, and the validity of the various methods for diagnosis was assessed. This was carried out according to a method described by Burbank and Parker for evaluating the quality of an image-guided breast intervention. We compared our results with the outcome of the COBRA study. Overall, all diagnostic strategies (NLBB, FNA, LCNB ultrasound and stereotactic guided) show comparable agreement rates. However, the miss rates differ: 2% for NLBB, 3% for COBRA (LCNB in study setting), 5% for FNA and 8-12% for LCNB in practice. Fine-needle aspiration was nonconclusive in 29%, and shows an overestimation for DCIS in 9%. The DCIS underestimate rate in NLBB was 8%. For the assessment of lesions consisting of microcalcifications only and to exclude malignancy in all other lesions, a 14-gauge needle should be used. Ultrasound-guided intervention can be performed in a large percentage of nonpalpable lesions. Lesions consisting only of microcalcifications on mammography need special attention.

Interobserver variability between general and expert pathologists during the histopathological assessment of large-core needle and open biopsies of non-palpable breast lesions.

The purpose of this study was to assess whether general pathologists are able to make as accurate and reproducible a diagnosis on large-core needle biopsies as on open breast biopsy specimens. A total of 688 patients underwent a stereotactic large-core (14G) needle biopsy and subsequent surgical excision of 718 non-palpable breast lesions. Forty-two pathologists from 10 departments of pathology (generalists) made a diagnosis on both the needle and open biopsy specimens. Afterwards, three pathologists and two radiologists with extensive experience in breast pathology (experts) diagnosed all of the biopsy specimens. The general pathologists made a similar histological diagnosis as the experts in 632 (88%) of the needle biopsies and 649 (90%) of the open biopsy specimens. Accordingly, the interobserver agreement for the diagnosis of large-core needle biopsies between the general and experts pathologists was excellent (kappa 0.83) and not significantly different from the interobserver agreement for the diagnosis of open breast biopsies (kappa 0.86). However, many inconsistencies were observed in the category of borderline lesions: only 24% of the large-core needle biopsies and 43% of the open biopsies with an expert diagnosis of 'borderline' were diagnosed similarly by the general pathologists. Additionally, the risk of benign/malignant inconsistencies between general pathologists and experts was approximately 1 in 55 for both needle and open biopsies.

Use of previous screening mammograms to identify features indicating cases that would have a possible gain in prognosis following earlier detection.

False-negative screening mammograms generally refer to breast cancers that were overlooked or misinterpreted at screening. An important question is whether earlier detection could have made a difference in the prognosis of the women concerned. We reviewed screening and diagnostic mammograms of 234 screen-detected and interval cancer cases (aged 44-84 years) diagnosed between 1991 and 1996 in the Nijmegen breast cancer screening programme. A lesion was visible on 117 (50%) of the screening mammograms prior to the diagnosis of breast cancer. Fifty-one out of the 117 cancers had poor prognostic characteristics at diagnosis (i.e. N+ and/or T2+) and could potentially have benefited from an earlier diagnosis ('possible gain'). The 'possible gain' cases were more often characterised by architectural distortion (29 vs. 10%; P=0.01) or a high-density mass (25 vs. 13%; P=0.06) on the mammogram prior to diagnosis than the 58 'no gain' cases. Our study shows that architectural distortion and non-spiculated high-density masses on the mammogram prior to diagnosis are associated with a possible gain in prognosis. Earlier detection of the carcinomas preceded by these signs may well have an impact on breast cancer mortality and thus warrant extra attention in radiological practice.

Diagnostic strategies in non-palpable breast lesions.

The number of non-palpable breast lesions is growing. Needle-localised breast biopsy (NLBB) is the gold standard for evaluating these lesions. Cost-saving techniques and less invasive alternatives such as core-needle biopsy (LCNB) and fine-needle aspiration (FNA) have emerged. The aim of this study was to find out if the lesions of patients who were sent directly for surgery to undergo a NLBB differed from lesions of patients who were send for a non-operative procedure. Furthermore, if a benign result was obtained, we assessed the total and kind of subsequent diagnostic procedures that were undertaken. A retrospective study on 718 women with 749 non-palpable breast lesions was performed. In 58% of women with non-palpable breast lesion, a non-surgical procedure was chosen. Lesions sent directly for surgery were more frequently not visible on ultrasound (62%) and mainly consisted of microcalcifications only (56%). In 45%, this primary surgical approach could have been avoided. If the non-operative procedure showed a non-malignant result, 41% of these women received an additional surgical diagnostic procedure. These figures obtained from routine daily practice show the importance of protocols in order to standardise diagnostic procedures and prevent unnecessary surgery.

Repeated mammographic screening reduces breast cancer mortality along the continuum of age.

OBJECTIVE: The optimal age boundaries for breast cancer screening are still under debate. A case-referent design was used to describe the effect of mammographic screening on breast cancer mortality along the continuum of age, based on a 20 year follow up period. SETTING: The population based breast cancer screening programme in Nijmegen, The Netherlands, which has biennially invited women over 35 years since 1975. METHODS: Cases, defined as women who died from primary breast cancer between 1987 and 1997, were selected from the group of women who received at least one invitation to the screening programme. For 157 cases, 785 women from the same group were selected as referents. Information on the index screening (the screening examination preceding diagnosis of the case) was collected for both cases and referents. The risk of dying from breast cancer was calculated per 10 year moving age group for women who had attended the index screening versus those who had not. RESULTS: The youngest 10 year age group showing an effect in our study were women aged 45-54 at their index screening. Breast cancer mortality for women in this group who attended the index screening was 32% lower, although not significant, than for women who did not (odds ratio (OR) 0.68, 95% confidence interval (95% CI) 0.33 to 1.41). This reduction in risk was not explained solely by an effect in women over 50 because the OR in women aged 45-49 was 0.56 (95% CI 0.20 to 1.61). Reductions in mortality became smaller with increasing age. Nevertheless, for women over 60 at index screening, participation in screening over a maximum 4 year period before diagnosis of the case yielded protective effects at least up to an age around 80. CONCLUSIONS: Although our results are based on a relatively small number of cases, they suggest that even in a programme with a 2 year screening interval there may be a benefit of starting screening around age 45. Also older women who participate at least once every 4 years still have much to gain from screening.