Nicholas M. Perry

Full-Field Digital versus Screen-Film Mammography: Comparison within the UK Breast Screening Program and Systematic Review of Published Data

PURPOSE To (a) compare the performance of full-field digital mammography (FFDM), using hard-copy image reading, with that of screen-film mammography (SFM) within a UK screening program (screening once every 3 years) for women aged 50 years or older and (b) conduct a meta-analysis of published findings along with the UK data. MATERIALS AND METHODS The study complied with the UK National Health Service Central Office for Research Ethics Committee guidelines; informed patient consent was not required, since analysis was carried out retrospectively after data anonymization. Between January 2006 and June 2007, a London population-based screening center performed 8478 FFDM and 31 720 SFM screening examinations, with modality determined by the type of machine available at the screening site. Logistic regression was used to assess whether breast cancer detection rates and recall rates differed between screening modalities. For the meta-analysis, random-effects models were used to combine study-specific estimates, if appropriate. RESULTS A total of 263 breast cancers were detected. After adjustment for age, ethnicity, area of residence, and type of referral, there was no evidence of differences between FFDM and SFM in terms of detection rates (0.68 [95% confidence interval {CI}: 0.47, 0.89] vs 0.72 [95% CI: 0.58, 0.85], respectively, per 100 screening mammograms; P = .74), recall rates (3.2% [95% CI: 2.8, 3.6] vs 3.4% [95% CI: 3.1, 3.6]; P = .44), positive predictive value (PPV) of an abnormal mammogram, or characteristics of detected tumors. Meta-analysis of data from eight studies showed a slightly higher detection rate for FFDM, particularly at 60 years of age or younger (pooled FFDM-SFM difference: 0.11 [95% CI: 0.04, 0.18] per 100 screening mammograms), but no clear modality differences in recall rates or PPVs. CONCLUSION Within a routine screening program, FFDM with hard-copy image reading performed as well as SFM in terms of process indicators; the meta-analysis was consistent with FFDM yielding detection rates at least as high as those for SFM.

Metastases to the breast revisited: radiological-histopathological correlation.

Metastases to the breast from extramammary tumours are infrequent. The main challenge in diagnosis is differentiating them from primary breast cancer. Radiologically this can be difficult as there are no specific imaging characteristics for metastases to the breast. Cytopathological evaluation, as well as full radiological assessment, is vital to avoid unnecessary surgery. Sources of primary tumours include a wide variety of cancers. In this pictorial review we illustrate a number of the commonest sources of primary tumours including lymphoma, lung, ovarian and cervical carcinoma, intestinal carcinoid and rare cases of Ewings sarcoma and malignant pigmented melanocytic schwannoma (low-grade malignant melanoma).

Life-course body size and perimenopausal mammographic parenchymal patterns in the MRC 1946 British birth cohort

Dense mammographic parenchymal patterns are associated with an increased risk of breast cancer. Certain features of body size have been found to be associated with breast cancer risk, but less is known about their relation to breast density. We investigated the association of birth size, childhood growth and life-course changes in body size with Wolfe grade in 1298 perimenopausal women from a British cohort of women born in 1946. The cohort benefits from repeated measures of body size in childhood and adulthood. We obtained mammograms for 90% of women who at age 53 years reported having previously had a mammogram. We found no associations with birth weight or maximum attained height. Body mass index (BMI) at age 53 years and breast size were independently and inversely associated with Wolfe grade (P-value for trend <0.001 for both). Women who reached puberty later were at a greater odds of a higher Wolfe grade than women who had an earlier puberty (odds ratio associated with a 1 year delay in menarche 1.14, 95% CI: 1.01–1.27, adjusted for BMI and breast size at mammography). A higher BMI at any age during childhood or adult life was associated with a reduction in the odds of a higher Wolfe grade, after controlling for breast size and BMI at mammography, for example, standardised odds ratio for height at age 7 was 0.72 (95% CI: 0.64, 0.81). These findings reveal the importance of taking life-course changes in body size, and not just contemporaneous measures, into account when using mammographic density as an intermediate marker for risk of breast cancer.

Comparison of a new and existing method of mammographic density measurement: intramethod reliability and associations with known risk factors.

Background: Mammographic density is one of the strongest risk factors for breast cancer. It is commonly measured by an interactive threshold method that does not fully use information contained in a mammogram. An alternative fully automated standard mammogram form (SMF) method measures density using a volumetric approach. Methods: We examined between-breast and between-view agreement, reliability, and associations of breast cancer risk factors with the threshold and SMF measures of breast density on the same set of 1,000 digitized films from 250 women who attended routine breast cancer screening by two-view mammography in 2004 at a London population-based screening center. Data were analyzed using random-effects models on transformed percent density. Results: Median (interquartile range) percent densities were 12.8% (5.0-22.3) and 21.8% (18.4-26.6) in the threshold and SMF methods, respectively. There was no evidence of systematic differences between left-right breasts or between views in either method. Reliability of a single measurement was lower in the SMF than in the threshold method (0.77 versus 0.92 for craniocaudal and 0.68 versus 0.89 for mediolateral oblique views). Increasing body mass index and parity were associated with reduced density in both methods; however, an increase in density with hormone replacement therapy use was found only with the threshold method. Conclusion: Established properties of mammographic density were observed for SMF percent density; however, this method had poorer left-right reliability than the threshold method and has yet to be shown to be a predictor of breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1148–54)

Ethnic variations in mammographic density: a British multiethnic longitudinal study.

It is not known whether the 20-30% lower breast cancer incidence rates in first-generation South Asian and Afro-Caribbean women relative to Caucasian women in the United Kingdom are reflected in mammographic density. The authors conducted a United Kingdom population-based multiethnic study of mammographic density at ages 50-64 years in 645 women. Data on breast cancer risk factors were obtained using a questionnaire/telephone interview. Threshold percent density was assessed on 5,277 digitized mammograms taken in 1995-2004 and was analyzed using multilevel models. Both ethnic minorities were characterized by more protective breast cancer risk factor distributions than Caucasians, such as later menarche, shorter stature, higher parity, earlier age at first birth, and less use of hormone therapy, but they had a higher mean body mass index; the last four factors were associated with lower mammographic density. Age-adjusted percent mammographic densities in Afro-Caribbeans and South Asians were 5.6% (95% confidence interval (CI): 3.5, 7.5) and 5.9% (95% CI: 3.6, 8.0) lower, respectively, than in Caucasians. Lower densities were partly attributed to higher body mass index, less use of hormone therapy, and a protective reproductive history, but these factors did not account entirely for ethnic differences, since fully adjusted mean densities were 1.3% (95% CI: -1.3, 3.7) and 3.8% (95% CI: 1.1, 6.3) lower, respectively. Ethnic differences in mammographic density are consistent with those for breast cancer risk.

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women

IntroductionSex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates.MethodsIn a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method.ResultsMean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m2 (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI.ConclusionsThese findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels.

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.

Benign biopsies in the prevalent round of breast screening : a review of 137 cases

In the first round of the National Health Service Breast Screening Programme, 35,533 women attended for screening at the two breast screening units served by St Bartholomews Hospital. Further assessment was necessary in 2212 women (6.2%), of whom 412 (1%) subsequently underwent surgical biopsy. Of these 137 had benign lesions. The predominant mammographic abnormality leading to biopsy was microcalcification in 55, a mass in 48, parenchymal asymmetry in 18 and architectural distortion in 16. Histology revealed fibrocystic change in 66, fibroadenoma in 27, radial scar/complex sclerosing lesion in 23, atypical ductal hyperplasia only in eight, and a variety of unusual benign lesions in 13. In an attempt to determine criteria which would minimize unnecessary biopsy of benign lesions in future, the mammographic and cytological features of these benign lesions were reviewed and compared with the final histology. The most common diagnostic problems were clustered and variable microcalcification, the radial scar/complex sclerosing lesion, and mammographic features shown to be atypical hyperplasia on histology.

Changes and tracking of mammographic density in relation to Pike's model of breast tissue aging: a UK longitudinal study

Percent mammographic density (PMD) is a strong marker of breast cancer risk. It may be a correlate of the rate of breast tissue aging, as proposed by Pike to explain breast cancer age‐incidence. We examined longitudinal changes in PMD in 645 breast screening attendees in London, UK, in which each had between 2 and 5 screens spanning 3–12 years at ages 50–65 years and compare these to Pikes model. Within‐woman PMD declined during these ages, with a slowing rate of decline. Annual rates of decline were 1.4% (95% confidence interval: 1.2–1.6), 0.7% (0.6–0.9) and 0.1% (–0.2 to 0.4) at ages 50, 57 and 64. Dense area declined similarly, but the absolute magnitude of the rate of increase of nondense area was almost double that of dense area. PMD dropped by 2.4% (1.4–3.4) on menopausal transition and increased by 2.4% (1.4–3.5) with the use of hormone therapy. Higher body mass index, greater parity and being Afro‐Caribbean or South Asian ethnicities were associated with lower PMD, but did not affect rate of change of PMD at these ages. Within‐woman rank correlation of PMD was 0.80 for readings taken 9 years apart. Effects of menopause and parity and the lack of effect of menarche on age‐specific PMD at these ages are consistent with the predicted determinants in Pikes model. A high degree of tracking of PMD indicates that at ages 50–65 years high‐risk women could be identified by a single early screen at age older than 50.

The impact of digital mammography on screening a young cohort of women for breast cancer in an urban specialist breast unit

ObjectiveTo compare the diagnostic performance of full-field digital mammography (FFDM) with screen-film mammography (SFM) in a corporate screening programme including younger women.MethodsData were available on 14,946 screening episodes, 5010 FFDM and 9936 SFM. Formal analysis was by logistic regression, adjusting for age and calendar year. FFDM is compared with SFM with reference to cancer detection rates, cancers presenting as clustering microcalcifications, recall rates and PPV of recall.ResultsOverall detection rates were 6.4 cancers per thousand screens for FFDM and 2.8 per thousand for SFM (p < 0.001). In women aged 50+ cancer detection was significantly higher for FFDM at 8.6 per thousand vs. 4.0 per thousand, (p = 0.002). In women <50, cancer detection was also significantly higher for FFDM at 4.3 per thousand vs. 1.4 per thousand, (p = 0.02). Cancers detected as clustering microcalcifications increased from 0.4 per thousand with SFM to 2.0 per thousand with FFDM. Rates of assessment recall were higher for FFDM (7.3% vs. 5.0%, p < 0.001). FFDM provided a higher PPV for assessment recall, (32 cancers/364 recalls, 8.8%) than SFM, (28 cancers/493 recalls, 5.7%).ConclusionsCancer detection rates were significantly higher for FFDM than for SFM, especially for women <50, and cancers detected as clustering microcalcifications.