Evaluation of digital mammography in diagnosis of breast cancer

Mammography has been digitized in all cases at our hospital. Digital mammography (MMG) of our hospital and its diagnostic accuracy were described in this report. Fuji Computed Radiography (FCR; Fuji Medical Systems, Tokyo, Japan) imaging plate was used and imaging data were processed with FCR 7000 or FCR 9000. Each image was output to a single hard copy. Sampling pitches for reading and output were 0.1 mm. The rate of breast cancer diagnosis by digital MMG was 67%, 95%, 94%, and 100% for unpalpable tumor, tumor less than ϕ 2 cm, tumor of ϕ 2 to 5 cm, and tumor greater than ϕ 5 cm, respectively, being 94% overall. Digital MMG enables us to establish goal-oriented image-processing conditions. The use of digital MMG, which provides an excellent diagnostic rate similar to that of screen-film MMG, is expected to became wide-spread in the near future.

     

Hereditary breast/ovarian and colorectal cancer genetics knowledge in a national sample of US physicians

Background: Clinically relevant genetics knowledge is essential for appropriate assessment and management of inherited cancer risk, and for effective communication with patients. This national physician survey assessed knowledge regarding basic cancer genetics concepts early in the process of introduction of predictive genetic testing for breast/ovarian and hereditary non-polyposis colorectal cancer (HNPCC) syndromes. Methods: A stratified random sample was selected from the American Medical Association Masterfile of all licensed physicians. In total, 1251 physicians (820 in primary care, 431 in selected subspecialties) responded to a 15 minute questionnaire (response rate 71%) in 1999–2000. Multivariate logistic regression analyses were conducted to identify demographic and practice characteristics associated with accurate response to three knowledge questions. Results: Of the study population, 37.5% was aware of paternal inheritance of BRCA1/2 mutations, and 33.8% recognised that these mutations occur in <10% of breast cancer patients. Only 13.1% accurately identified HNPCC gene penetrance as ⩾50%. Obstetrics/gynaecology physicians, oncologists, and general surgeons were significantly more likely than general and family practitioners to respond accurately to the breast/ovarian questions, as were gastroenterologists to the HNPCC question. Conclusions: These nationally representative data indicate limited physician knowledge about key cancer genetics concepts in 1999–2000, particularly among general primary care physicians. Specialists were more knowledgeable about syndromes they might treat or refer elsewhere. Recent dissemination of practice guidelines and continued expansion of relevant clinical literature may enhance knowledge over time. In addition to educational efforts to assist physicians with the growing knowledge base, more research is needed to characterise the organisational changes required within the healthcare system to provide effective cancer genetics services.     

Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population

In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974–2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a ‘triple-negative breast cancer'' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria.     

EMAS position statement: Individualized breast cancer screening versus population-based mammography screening programmes

Introduction

Breast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well established method to detect breast cancer.

Aims

The aim of the position statement is to review critically the advantages and shortcomings of population based mammography screening.

Materials and methods

Literature review and consensus of expert opinion.

Results and conclusion

Mammography screening programmes vary worldwide. Thus there are differences in the age at which screening is started and stopped and in the screening interval. Furthermore differences in screening quality (such as equipment, technique, resolution, single or double reading, recall rates) result in a sensitivity varying from 70% to 94% between studies. Reporting results of screening is subject to different types of bias such as overdiagnosis. Thus because of the limitations of population-based mammography screening programmes an algorithm for individualized screening is proposed.     

EMAS position statement: Individualized breast cancer screening versus population-based mammography screening programmes

IntroductionBreast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well established method to detect breast cancer.AimsThe aim of the position statement is to review critically the advantages and shortcomings of population based mammography screening.Materials and methodsLiterature review and consensus of expert opinion.Results and conclusionMammography screening programmes vary worldwide. Thus there are differences in the age at which screening is started and stopped and in the screening interval. Furthermore differences in screening quality (such as equipment, technique, resolution, single or double reading, recall rates) result in a sensitivity varying from 70% to 94% between studies. Reporting results of screening is subject to different types of bias such as overdiagnosis. Thus because of the limitations of population-based mammography screening programmes an algorithm for individualized screening is proposed.     

A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center

The medical community and general population have become aware that genetic testing is available to look for BRCA1 and BRCA2 mutations. However, criteria for who should be referred for genetic counseling and possible subsequent testing have yet to be determined, and many genetics centers have been overwhelmed by the demand for service. We set out to develop a family history assessment tool (FHAT) that could be used by physicians to select individuals for genetic counseling. Arbitrarily, we chose individuals who would have an approximate doubling of their lifetime risk for breast or ovarian cancer. The FHAT was then applied to 184 unrelated families, with an index patient who had breast or ovarian cancer and who had accepted the offer of BRCA1 BRCA2 testing. Data were compiled to compare the number of individuals who would have been referred for genetic counseling and the number of mutation-positive individuals who would have been screened out from counseling using FHAT, the tables from Claus, and the BRCAPRO system. In this population, FHAT was effective in minimizing both the number of referrals and the likelihood of missing women who were later found to be mutation-positive.     

Decreased serum miR-181a is a potential new tool for breast cancer screening

Breast cancer (BC) screening is important for early detection, but conventional tumor markers lack the desired sensitivity. Aberrant microRNA (miRNA) expression plays an important role in tumor formation and development. Thus, serum miRNAs represent potential BC biomarkers. microRNA-181a (miR-181a) is deregulated in many types of human cancer and is a key oncogenic regulator, but the relationship between serum miR-181a and BC diagnosis has not been investigated. This study investigated serum miR-181a levels in BC patients and healthy controls and compared the diagnostic value of serum miR-181a as a BC tumor marker with the conventional tumor markers CA153 and CEA. Serum miR-181a and miR-16 (as a control) were quantified by real-time quantitative RT-PCR in 20 plasma samples. The promising results prompted analysis of 227 additional samples. The levels of CA153 and CEA were measured using electrochemiluminescence assays. Median miR-181a levels were significantly lower in patients with BC compared to healthy controls (P=0.001). ROC analysis demonstrated the sensitivity and specificity of miR-181a for BC diagnosis at 70.7 and 59.9%, respectively, whereas the sensitivities of CA153 and CEA were 10.53 and 9.21%. As a tumor marker, serum miR-181a expressed a higher level of sensitivity [55.28% (68/123)] in the early stage of BC diagnosis (ductal carcinoma in situ, TNM I and II) than the CA153 and CEA markers (8.13 and 7.32%, respectively). There were no significant associations between miR-181a levels and other clinicopathological parameters. These results suggest that serum miR-181a may represent a novel biomarker for primary BC as well as for early stage BC diagnosis. In combination with other markers, serum miR-181a may improve the sensitivity of BC screening.     

The effect of a church-based breast cancer screening education program on mammography rates among African-American women

This study examines the effectiveness of breast cancer screening education programs on mammography rates among African-American women 40 years of age and over. We conducted two types of educational programs in community settings, primarily in African-American churches. Three-month follow-up interviews were used to determine whether women who participated in programming were more likely to get a mammogram if they had not had a mammogram in the last year. Our results demonstrate that the educational programs significantly increased the likelihood of getting a mammogram when compared to a control group that received no educational programming. Further, we found that the programs were effective for motivating breast cancer screening in housing projects as well as in the churches, and that the effectiveness of the programs remained even when we controlled for socioeconomic status, depression, and age.     

Comparative study of the histopathology of breast cancer in a screened and unscreened population investigated by mammography

The histopathology of 360 surgical resections for breast cancer in a consecutive series of patients aged 45-69 years from 1979-1983 is described. Two hundred and seventeen patients who were offered screening (screened patients) were compared with 143 patients who were referred as out-patients with breast problems and were not offered screening (unscreened patients). Both groups were investigated by mammography. Comparisons between tumour staging, grading and quadrant involvement are reported. In the screened patients 31% were in the in-situ stage or had an invasive carcinoma less than 1.0 cm in maximum diameter, compared with 7% in the unscreened patients. Conversely 26% of the screened patients had cancers greater than 2.0 cm compared with 52% in the unscreened group. The percentage of cancer patients with lymph node metastases was comparable in both 1.0-2.0 cm and greater than 2.0 cm groups of invasive carcinoma. There were more multiquadrant cancers in the unscreened patients (32%) than screened patients (17%) and this was mainly due to differences in the incidence of carcinomas 1.0-2.0 cm in diameter. This suggests that invasive tumours of comparable size are more likely to produce symptoms leading to detection if multiquadrant. Multicentric cancers were more common in unscreened patients. Differences in the histological grading related to tumour size were found within the screened and unscreened groups but not between the two groups.     

Implications of pathologist concordance for breast cancer assessments in mammography screening from age 40 years

Three pathologists reviewed slides and reports of cancers arising in both the study and control populations of the U.K. trial of annual mammography screening from age 40 years. A total of 875 cases were scored independently as noninvasive, microinvasive, or invasive cancer, with the last also evaluated for histology grade, type, and lymphatic vascular invasion. Of these, 870 (99.2%) were confirmed malignant, 1 case had cytology only, and 5 were judged by all reviewers as benign. Reviewer complete concordance for the three classes of malignancy was achieved in 826 (95%) and majority agreement in 31 (3.6%) of 870 with complete data. All three readers recorded grade in 736 cancers, giving a kappa statistic of 0.69, 0.52, and 0.66 for grades I, II, and III, respectively, and 0.61 overall. Agreement that the cancer was special type or not was obtained in 671 (89.0%) with complete concordance in the nature of the type in 504 and majority view in 167; another 58 (7.7%) were characterised as "part special" pattern, with type disagreement in 23 (3%). The kappa statistic for single type subcategories in those cancers was substantial, at 0.68 overall. This improved to 0.76 for the last 230 invasive cancers after the pathologists agreed more explicit criteria for type discrimination. There was almost perfect agreement between original and review diagnosis of breast malignancy for both noninvasive/microinvasive and invasive cancer (kappa 0.84 and 0.91, respectively), justifying confidence in the diagnosis of breast cancer by U.K. pathologists. The specialists agreed substantially on qualitative histology features of type and grade of cancers, and improved further for typing by defining criteria. These consensus data, along with invasive size and node status, are reliable for use as surrogate measures of outcome, and to enhance interpretation of effect, when the trial case population sources are disclosed.     

Physicians' attitudes towards mammography and prophylactic surgery for hereditary breast/ovarian cancer risk and subsequently published guidelines

After a BRCA mutation has been identified in the context of hereditary breast/ovarian cancer (HBOC), mammographic screening and prophylactic surgery are two of the main options available to those responsible for the clinical management of healthy women. The aim of this study was to describe the attitudes of specialists towards the clinical management of women with an HBOC risk: this information was collected prior to the publication of the recent French guidelines. A random national sample of 1169 French surgeons, gynaecologists and obstetricians was surveyed using a mailed questionnaire, to which 700 of these physicians (60%) responded. When dealing with a BRCA mutated woman, 88.6% of the respondents said they would recommend mammographic screening, but only 27.1% would recommend that it should be carried out annually from the age of 30 years onwards, as recommended in the French guidelines; 10.9% would find it acceptable to propose prophylactic mastectomy from the age of 30 years, and 22.9% would find it acceptable to propose prophylactic oophorectomy from the age of 35 years. The specialists who agreed with recommending breast/ovarian cancer genetic testing also had more positive attitudes towards prophylactic mastectomy (adj OR = 3.4, 95% CI = 1.4-8.2), as did those who had previously recommended prophylactic mastectomy when gene testing was not yet available (adj OR = 2.06, 95% CI = 1.23-3.44). The respondents' attitudes towards prophylactic oophorectomy and mastectomy were significantly associated (adj OR = 3.9; 95% CI = 2.3-6.5). Previous recommendation of prophylactic mastectomy was associated (P < 0.01) with a higher level of knowledge of breast/ovarian cancer genetics and with medical practice in this field. French physicians' attitudes towards mammographic screening and prophylactic surgery were not in complete agreement with the subsequently published French guidelines, the impact of which has now to be considered. Constantly evolving knowledge about the efficacy of preventive intervention will give practitioners new elements to integrate into their counselling.     

Clinical follow-up and breast and ovarian cancer screening of true BRCA1/2 noncarriers: a qualitative investigation

PurposeMost women from BRCA1/2 mutation–positive families who did not inherit the familial mutation have breast and ovarian cancer risks similar to those of women of the same age in the general population. However, recent studies suggest that some of these noncarriers may exhibit screening practices that may be considered as excessive compared to general population screening guidelines. Reasons for such tendencies remain largely unknown. This study aims to better understand how the implications of a noncarrier status are explained to these women and how their own realization of this status affects their screening behaviors.MethodsA qualitative study was conducted with five focus groups (n = 28) in Quebec City and Montreal, Canada.ResultsThematic analysis of the discussions highlighted four major themes: (i) acquiring a noncarrier identity takes place progressively; (ii) noncarriers show a range of opinions about screening; (iii) noncarriers have mixed feelings about the follow-up by their physicians and gynecologists; and (iv) noncarriers need more information in a context where genetics progresses ever more rapidly.ConclusionOur results provide novel insights regarding the physician–patient interaction and the organizational aspects of the health-care system that may significantly impact the cancer screening practices of BRCA1/2 noncarriers.     

Relation between breast cancer mortality and screening effectiveness: systematic review of the mammography trials

The mammography screening trials have shown varying results. This could be because screening was better in some trials than in others at advancing the time of diagnosis. If so, more cancers would be identified in such trials relative to the control group, and fewer of the cancers would have reached an advanced stage. I performed a systematic review of the mammography screening trials using metaregression. Finding many cancers was not related to the size of the reduction in breast cancer mortality (p = 0.19 after seven and p = 0.73 after 13 years of follow-up). In contrast, finding few cancers in stage II and above predicted a larger reduction in breast cancer mortality (p = 0.04 and p = 0.006). This expected association was also found for node-positive cancers (p = 0.008 and p = 0.04). However, a screening effectiveness of zero (same proportion of node-positive cancers in the screened group as in the control group) predicted a significant 16% reduction in breast cancer mortality after 13 years (95% confidence interval, 9% to 23% reduction). This can only occur if there is bias. Further analyses uncovered bias in both assessment of the cause of death and of the number of cancers in advanced stages. Consequently, the differences in the reported reductions in breast cancer mortality cannot be explained by differences in screening effectiveness. Given that the size of the bias was similar to the estimated screening effect, screening appeared ineffective.     

Cytogenetics and molecular genetics of ovarian cancer

Genetic alterations identified in human ovarian tumors by conventional banding, fluorescence in situ hybridization, comparative genomic hybridization, chromosome microdissection, loss of heterozygosity, chromosome microcell-mediated chromosome transfer, and microarray gene expression analysis are summarized and correlated. The significance of these findings with respect to pathologic classification and clinical application are discussed.