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1.  Effect on biopsy technique of the breast imaging reporting and data system (BI-RADS) for nonpalpable mammographic abnormalities 
Canadian Journal of Surgery  2002;45(4):259-263.
Objective
To determine if the breast imaging reporting and data system (BI-RADS) defines a group of patients with mammographic abnormalities in whom stereotactic core needle biopsy (SCNB) is appropriate.
Design
A blinded retrospective validation sample.
Setting
A university-affiliated hospital.
Patients
One hundred and nine consecutive patients who underwent fine-wire localization breast biopsy (FWLB) between Jan. 1, 1994, and June 1, 1999, with a known final pathological diagnosis.
Intervention
Blinded mammographic review and classification using the BI-RADS; review of corresponding pathological findings from FWLBs.
Outcome measures
Correlation of pathological findings with each BI-RADS category and analysis of the predictive value of clinical and radiologic features.
Results
BI-RADS findings were as follows: 0 malignant lesions in 10 category 3 cases, 18 malignant lesions (3 in situ, 15 invasive) in 68 category 4 cases and 24 malignant lesions (8 in situ and 16 invasive) in 31 category 5 cases. There was 1 malignant lesion in 22 category 4 cases in women younger than 50 years.
Conclusions
SCNB should be applied to BI-RADS categories 3 and 4 (< 50 yr of age). FWLB should be reserved for category 4 (> 50 yr of age) and category 5 cases. This algorithm will reduce the morbidity and cost of breast biopsies in patients with nonpalpable mammographic abnormalities.
PMCID: PMC3684677  PMID: 12174979
2.  Screening Mammography for Women Aged 40 to 49 Years at Average Risk for Breast Cancer 
Executive Summary
Objective
The aim of this review was to determine the effectiveness of screening mammography in women aged 40 to 49 years at average risk for breast cancer.
Clinical Need
The effectiveness of screening mammography in women aged over 50 years has been established, yet the issue of screening in women aged 40 to 49 years is still unsettled. The Canadian Task Force of Preventive Services, which sets guidelines for screening mammography for all provinces, supports neither the inclusion nor the exclusion of this screening procedure for 40- to 49-year-old women from the periodic health examination. In addition to this, 2 separate reviews, one conducted in Quebec in 2005 and the other in Alberta in 2000, each concluded that there is an absence of convincing evidence on the effectiveness of screening mammography for women in this age group who are at average risk for breast cancer.
In the United States, there is disagreement among organizations on whether population-based mammography should begin at the age of 40 or 50 years. The National Institutes of Health, the American Association for Cancer Research, and the American Academy of Family Physicians recommend against screening women in their 40s, whereas the United States Preventive Services Task Force, the National Cancer Institute, the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists recommend screening mammograms for women aged 40 to 49 years. Furthermore, in comparing screening guidelines between Canada and the United States, it is also important to recognize that “standard care” within a socialized medical system such as Canada’s differs from that of the United States. The National Breast Screening Study (NBSS-1), a randomized screening trial conducted in multiple centres across Canada, has shown there is no benefit in mortality from breast cancer from annual mammograms in women randomized between the ages of 40 and 49, relative to standard care (i.e. physical exam and teaching of breast-self examination on entry to the study, with usual community care thereafter).
At present, organized screening programs in Canada systematically screen women starting at 50 years of age, although with a physician’s referral, a screening mammogram is an insured service in Ontario for women under 50 years of age.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined, whereas mortality is decreasing, though at a slower rate. These decreasing mortality rates may be attributed to screening and advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the SEER cancer registry in the United States indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20-year period (from 2.7 to 25 per 100,000).
The incidence of breast cancer is lower in women aged 40 to 49 years than in women aged 50 to 69 years (about 140 per 100,000 versus 500 per 100,000 women, respectively), as is the sensitivity (about 75% versus 85% for women aged under and over 50, respectively) and specificity of mammography (about 80% versus 90% for women aged under and over 50, respectively). The increased density of breast tissue in younger women is mainly responsible for the lower accuracy of this procedure in this age group. In addition, as the proportion of breast cancers that occur before the age of 50 are more likely to be associated with genetic predisposition as compared with those diagnosed in women after the age of 50, mammography may not be an optimal screening method for younger women.
Treatment options vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy, and/or radiotherapy.
Surgery is the first-line intervention for biopsy confirmed tumours. The subsequent use of radiation, chemotherapy, or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is noninvasive.
With such controversy as to the effectiveness of mammography and the potential risk associated with women being overtreated or actual cancers being missed, and the increased risk of breast cancer associated with exposure to annual mammograms over a 10-year period, the Ontario Health Technology Advisory Committee requested this review of screening mammography in women aged 40 to 49 years at average risk for breast cancer. This review is the first of 2 parts and concentrates on the effectiveness of screening mammography (i.e., film mammography, FM) for women at average risk aged 40 to 49 years. The second part will be an evaluation of screening by either magnetic resonance imaging or digital mammography, with the objective of determining the optimal screening modality in these younger women.
Review Strategy
The following questions were asked:
Does screening mammography for women aged 40 to 49 years who are at average risk for breast cancer reduce breast cancer mortality?
What is the sensitivity and specificity of mammography for this age group?
What are the risks associated with annual screening from ages 40 to 49?
What are the risks associated with false positive and false negative mammography results?
What are the economic considerations if evidence for effectiveness is established?
The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the International Network of Agencies for Health Technology Assessment.
Keywords used in the search were breast cancer, breast neoplasms, mass screening, and mammography.
In total, the search yielded 6,359 articles specific to breast cancer screening and mammography. This did not include reports on diagnostic mammograms. The search was further restricted to English-language randomized controlled trials (RCTs), systematic reviews, and meta-analyses published between 1995 and 2005. Excluded were case reports, comments, editorials, and letters, which narrowed the results to 516 articles and previous health technology policy assessments.
These were examined against the criteria outlined below. This resulted in the inclusion of 5 health technology assessments, the Canadian Preventive Services Task Force report, the United States Preventive Services Task Force report, 1 Cochrane review, and 8 RCTs.
Inclusion Criteria
English-language articles, and English and French-language health technology policy assessments, conducted by other organizations, from 1995 to 2005
Articles specific to RCTs of screening mammography of women at average risk for breast cancer that included results for women randomized to studies between the ages of 40 and 49 years
Studies in which women were randomized to screening with or without mammography, although women may have had clinical breast examinations and/or may have been conducting breast self-examination.
UK Age Trial results published in December 2006.
Exclusion Criteria
Observational studies, including those nested within RCTs
RCTs that do not include results on women between the ages of 40 and 49 at randomization
Studies in which mammography was compared with other radiologic screening modalities, for example, digital mammography, magnetic resonance imaging or ultrasound.
Studies in which women randomized had a personal history of breast cancer.
Intervention
Film mammography
Comparators
Within RCTs, the comparison group would have been women randomized to not undergo screening mammography, although they may have had clinical breast examinations and/or have been conducting breast self-examination.
Outcomes of Interest
Breast cancer mortality
Summary of Findings
There is Level 1 Canadian evidence that screening women between the ages of 40 and 49 years who are at average risk for breast cancer is not effective, and that the absence of a benefit is sustained over a maximum follow-up period of 16 years.
All remaining studies that reported on women aged under 50 years were based on subset analyses. They provide additional evidence that, when all these RCTs are taken into account, there is no significant reduction in breast cancer mortality associated with screening mammography in women aged 40 to 49 years.
Conclusions
There is Level 1 evidence that screening mammography in women aged 40 to 49 years at average risk for breast cancer is not effective in reducing mortality.
Moreover, risks associated with exposure to mammographic radiation, the increased risk of missed cancers due to lower mammographic sensitivity, and the psychological impact of false positives, are not inconsequential.
The UK Age Trial results published in December 2006 did not change these conclusions.
PMCID: PMC3377515  PMID: 23074501
3.  Evaluation of breast amorphous calcifications by a computer-aided detection system in full-field digital mammography 
The British Journal of Radiology  2012;85(1013):517-522.
Objectives
The purpose of this study was to evaluate the performance of a direct computer-aided detection (d-CAD) system integrated with full-field digital mammography (FFDM) in assessment of amorphous calcifications.
Methods
From 1438 consecutive stereotactic-guided biopsies, FFDM images with amorphous calcifications were selected for retrospective evaluation by d-CAD in 122 females (mean age, 56 years; range, 35–84 years). The sensitivity, specificity, accuracy and false-positive rate of the d-CAD system were calculated in the total group of 124 lesions and in the subgroups based on breast density, mammographic lesion distribution and extension. Logistic regression analysis was used to stratify the risk of malignancy by patient risk factors and age.
Results
The d-CAD marked all (36/36) breast cancers, 85% (11/13) of the high-risk lesions and 80% (60/75) of benign amorphous calcifications (p<0.01) correctly. The sensitivity, specificity and diagnostic accuracy for the combined malignant and “high-risk” lesions was 96, 80 and 86%, respectively. The likelihood of malignancy was 29%. There was no significant difference between the marking of fatty or dense breasts (p>0.05); however, d-CAD marks showed differences for small (<7 mm) lesions (p=0.02) and clustered calcifications (p=0.03). The false-positive rate of d-CAD was 1.76 marks per full examination.
Conclusion
The d-CAD system correctly marked all biopsy-proven breast cancers and a large number of biopsy-proven high-risk lesions that presented as amorphous calcifications. Given our 29% likelihood of malignancy, imaging-guided biopsy appears to be a reasonable recommendation in cases of amorphous calcifications marked by d-CAD.
doi:10.1259/bjr/31850970
PMCID: PMC3479871  PMID: 22556404
4.  CAD May Not be Necessary for Microcalcifications in the Digital era, CAD May Benefit Radiologists for Masses 
Objective:
The aim of this study was to evaluate the effectiveness of computer-aided detection (CAD) to mark the cancer on digital mammograms at the time of breast cancer diagnosis and also review retrospectively whether CAD marked the cancer if visible on any available prior mammograms, thus potentially identifying breast cancer at an earlier stage. We sought to determine why breast lesions may or may not be marked by CAD. In particular, we analyzed factors such as breast density, mammographic views, and lesion characteristics.
Materials and Methods:
Retrospective review from 2004 to 2008 revealed 3445 diagnosed breast cancers in both symptomatic and asymptomatic patients; 1293 of these were imaged with full field digital mammography (FFDM). After cancer diagnosis, in a retrospective review held by the radiologist staff, 43 of these cancers were found to be visible on prior-year mammograms (false-negative cases); these breast cancer cases are the basis of this analysis. All cases had CAD evaluation available at the time of cancer diagnosis and on prior mammography studies. Data collected included patient demographics, breast density, palpability, lesion type, mammographic size, CAD marks on current- and prior-year mammograms, needle biopsy method, pathology results (core needle and/or surgical), surgery type, and lesion size.
Results:
On retrospective review of the mammograms by the staff radiologists, 43 cancers were discovered to be visible on prior-year mammograms. All 43 cancers were masses (mass classification included mass, mass with calcification, and mass with architectural distortion); no pure microcalcifications were identified in this cohort. Mammograms with CAD applied at the time of breast cancer diagnosis were able to detect 79% (34/43) of the cases and 56% (24/43) from mammograms with CAD applied during prior year(s). In heterogeneously dense/extremely dense tissue, CAD marked 79% (27/34) on mammograms taken at the time of diagnosis and 56% (19/34) on mammograms with CAD applied during the prior year(s). At time of diagnosis, CAD marked lesions in 32% (11/34) on the craniocaudal (CC) view, 21% (7/34) on the mediolateral oblique (MLO) view. Lesion size of those marked by CAD or not marked were similar, the average being 15 and 12 mm, respectively.
Conclusion:
CAD marked cancers on mammograms at the time of diagnosis in 79% of the cases and in 56% of the cases from the mammograms with CAD applied in the prior year(s). Our review demonstrated that CAD can mark invasive breast carcinomas in even dense breast tissue. CAD marked a significant portion on the CC view only, which may be an indicator to radiologists to be especially vigilant when a lesion is marked on this view.
doi:10.4103/2156-7514.99179
PMCID: PMC3424776  PMID: 22919559
Breast carcinoma; breast imaging; calcifications; computer-aided detection; digital mammography
5.  Retrieval Rate and Accuracy of Ultrasound-Guided 14-G Semi-Automated Core Needle Biopsy of Breast Microcalcifications 
Korean Journal of Radiology  2014;15(1):12-19.
Objective
To evaluate the retrieval rate and accuracy of ultrasound (US)-guided 14-G semi-automated core needle biopsy (CNB) for microcalcifications in the breast.
Materials and Methods
US-guided 14-G semi-automated CNB procedures and specimen radiography were performed for 33 cases of suspicious microcalcifications apparent on sonography. The accuracy of 14-G semi-automated CNB and radiology-pathology concordance were analyzed and the microcalcification characteristics between groups with successful and failed retrieval were compared.
Results
Thirty lesions were successfully retrieved and the microcalcification retrieval rate was 90.9% (30/33). Thirty lesions were successfully retrieved. Twenty five were finally diagnosed as malignant (10 invasive ductal carcinoma, 15 ductal carcinoma in situ [DCIS]) and five as benign. After surgery and mammographic follow-up, the 25 malignant lesions comprised 12 invasive ductal carcinoma and 13 DCIS. Three lesions in the failed retrieval group (one DCIS and two benign) were finally diagnosed as two DCIS and one benign after surgery. The accuracy of 14-G semi-automated CNB was 90.9% (30/33) because of two DCIS underestimates and one false-negative diagnosis. The discordance rate was significantly higher in the failed retrieval group than in the successful retrieval group (66.7% vs. 6.7%; p < 0.05). Punctate calcifications were significantly more common in the failed retrieval group than in the successful retrieval group (66.7% vs. 3.7%; p < 0.05).
Conclusion
US-guided 14-G semi-automated CNB could be a useful procedure for suspicious microcalcifications in the breast those are apparent on sonography.
doi:10.3348/kjr.2014.15.1.12
PMCID: PMC3909843  PMID: 24497787
Breast biopsy; Breast ultrasound; Breast neoplasms, microcalcifications
6.  Correlation between mammographic and sonographic findings and prognostic factors in patients with node-negative invasive breast cancer 
The British Journal of Radiology  2011;84(997):19-30.
Objectives
The purpose of this study was to correlate sonographic and mammographic findings with prognostic factors in patients with node-negative invasive breast cancer.
Methods
Sonographic and mammographic findings in 710 consecutive patients (age range 21–81 years; mean age 49 years) with 715 node-negative invasive breast cancers were retrospectively evaluated. Pathology reports relating to tumour size, histological grade, lymphovascular invasion (LVI), extensive intraductal component (EIC), oestrogen receptor (ER) status and HER-2/neu status were reviewed and correlated with the imaging findings. Statistical analysis was performed using logistic regression analysis and intraclass correlation coefficient (ICC).
Results
On mammography, non-spiculated masses with calcifications were associated with all poor prognostic factors: high histological grade, positive LVI, EIC, HER-2/neu status and negative ER. Other lesions were associated with none of these poor prognostic factors. Hyperdense masses on mammography, the presence of mixed echogenicity, posterior enhancement, calcifications in-or-out of masses and diffusely increased vascularity on sonography were associated with high histological grade and negative ER. Associated calcifications on both mammograms and sonograms were correlated with EIC and HER-2/neu overexpression. The ICC value for the disease extent was 0.60 on mammography and 0.70 on sonography.
Conclusion
Several sonographic and mammographic features can have a prognostic value in the subsequent treatment of patients with node-negative invasive breast cancer. Radiologists should pay more attention to masses that are associated with calcifications because on both mammography and sonography associated calcifications were predictors of positive EIC and HER-2/neu overexpression.
doi:10.1259/bjr/92960562
PMCID: PMC3473801  PMID: 20682592
7.  Lobular intraepithelial neoplasia arising within breast fibroadenoma 
BMC Research Notes  2013;6:267.
Background
Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer.
Case presentation
A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia.
Conclusions
The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating follow-up. According to our experience, when patients are older than 40 years and have a familial history of breast cancer, we prefer to carry out lumpectomy with follow up to avoid the risk of underestimation in situ foci within the lump.
doi:10.1186/1756-0500-6-267
PMCID: PMC3716517  PMID: 23849288
Fibroadenoma; Lobular intraepithelial neoplasia; Popcorn-like calcifications
8.  US-Guided Vacuum-Assisted Biopsy of Microcalcifications in Breast Lesions and Long-Term Follow-Up Results 
Korean Journal of Radiology  2008;9(6):503-509.
Objective
To evaluate the diagnostic accuracy of the use of an ultrasonography (US)-guided vacuum-assisted biopsy for microcalcifications of breast lesions and to evaluate the efficacy of the use of US-guided vacuum-assisted biopsy with long-term follow-up results.
Materials and Methods
US-guided vacuum-assisted biopsy cases of breast lesions that were performed between 2002 and 2006 for microcalcifications were retrospectively reviewed. A total of 62 breast lesions were identified where further pathological confirmation was obtained or where at least two years of mammography follow-up was obtained. These lesions were divided into the benign and malignant lesions (benign and malignant group) and were divided into underestimated group and not-underestimated lesions (underestimated and not-underestimated group) according to the diagnosis after a vacuum-assisted biopsy. The total number of specimens that contained microcalcifications was analyzed and the total number of microcalcification flecks as depicted on specimen mammography was analyzed to determine if there was any statistical difference between the groups.
Results
There were no false negative cases after more than two years of follow-up. Twenty-nine lesions were diagnosed as malignant (two invasive carcinomas and 27 carcinoma in situ lesions). Two of the 27 carcinoma in situ lesions were upgraded to invasive cancers after surgery. Among three patients diagnosed with atypical ductal hyperplasia, the diagnosis was upgraded to a ductal carcinoma in situ after surgery in one patient. There was no statistically significant difference in the number of specimens with microcalcifications and the total number of microcalcification flecks between the benign group and malignant group of patients and between the underestimated group and not-underestimated group of patients.
Conclusion
US-guided vacuum-assisted biopsy can be an effective alternative to stereotactic-guided vacuum-assisted biopsy in cases where microcalcifications are visible with the use of high-resolution US.
doi:10.3348/kjr.2008.9.6.503
PMCID: PMC2627239  PMID: 19039266
Breast, US; Breast, Biopsy; Breast, Calcification
9.  Association of Mammographic Density with Pathologic Findings 
Background
Breast cancer is one of the most common cancers in the world and is the first cause of death due to cancer among women. Mammography is the best screening method and mammographic density, which determines the percentage of fibro glandular tissue of breast, is one of the strongest risk factors of breast cancer. Because benign and malignant lesions may present as dense lesions in mammography so it is necessary to take a core biopsy of any suspicious lesions to evaluate pathologic findings.
Objectives
The aim of this study was to assess the association between mammographic density and histopathological findings in Iranian population. Moreover, we assessed the correlation between mammographic density and protein expression profile. We indeed, determined the accuracy and positive predictive value and negative predictive value of mammographic reports in our center.
Patients and Method
This study is a cross-sectional study carried out among 131 eligible women who had referred to imaging center for mammographic examination and had been advised to take biopsy of breast tissue. All participants of the study had filled out the informed consent. Pathologic review was performed blinded to the density status. Patients were divided into low density breast tissue group (ACR density group 1-2) and high density breast tissue group (ACR 3, 4) and data was compared between these two groups. Statistical analysis performed using SPSS for windows, version 11.5. We used chi-square, t-test, and logistic regression test for analysis and Odds Ratio calculated where indicated.
Results
In patients with high breast densities, malignant cases (61.2%) were significantly more in comparison to patients with low breast densities (37.3%) (P= 0.007, OR=2.66 95% CI=1.29-5.49). After adjusting for age, density was associated with malignancy in age groups <46 years (P=0.007), and 46-60 years (P=0.024) but not in age group >60yrs (P=0.559). Adjusting for menopausal status, density showed association with malignancy in both pre-menopause (P=0.041) and menopause (P=0.010) patients. Using logistic regression test, only age and density showed independent association with risk of breast cancer. No association was found between density and protein profile expression. Mammographic method has a false negative percent of 10.3% for negative BI-RADS group and a Positive Predictive Value (PPV) of 69.6% for positive BI-RADS group. PPVs for BI-RADS 4a, 4b, 4c and 5 were 16%, 87.5%, 84.6%, and 91.5% respectively. NPVs for BI-RADS 1, 2 and 3 were 66.7%, 95.8% and 90.0% respectively.
Conclusions
In this study we found that increasing in mammographic density is associated with an increase in malignant pathology reports. Expression of ER, PR and HER-2 receptors didn't show association with density. Our mammographic reports had a sensitivity of 94.1% and a specificity of 55.6%, which shows that our mammography is an acceptable method for screening breast cancer in this center.
doi:10.5812/ircmj.16698
PMCID: PMC3955519  PMID: 24693404
Mammographic Density; Pathology; Receptors, Estrogen; Receptors, Progesterone
10.  Role of Computer-Aided Detection in Very Small Screening Detected Invasive Breast Cancers 
Journal of Digital Imaging  2012;26(3):572-577.
This study aims to assess computer-aided detection (CAD) performance with full-field digital mammography (FFDM) in very small (equal to or less than 1 cm) invasive breast cancers. Sixty-eight invasive breast cancers less than or equal to 1 cm were retrospectively studied. All cases were detected with FFDM in women aged 49–69 years from our breast cancer screening program. Radiological characteristics of lesions following BI-RADS descriptors were recorded and compared with CAD sensitivity. Age, size, BI-RADS classification, breast density type, histological type of the neoplasm, and role of the CAD were also assessed. Per-study specificity and mass false-positive rate were determined by using 100 normal consecutive studies. Thirty-seven (54.4 %) masses, 17 (25 %) calcifications, 6 (8.8 %) masses with calcifications, 7 (10.3 %) architectural distortions, and 1 asymmetry (1.5 %) were found. CAD showed an overall sensitivity of 86.7 % (masses, 86.5 %; calcifications, 100 %; masses with calcifications, 100 %; and architectural distortion, 57.14 %), CAD failed to detect 9 out of 68 cases: 5 of 37 masses, 3 of 7 architectural distortions, and 1 of 1 asymmetry. Fifteen out of 37 masses were hyperdense, and all of them were detected by CAD. No association was seen among mass morphology or margins and detectability. Per-study specificity and CAD false-positive rate was 26 % and 1.76 false marks per study. In conclusion, CAD shows a high sensitivity and a low specificity. Lesion size, histology, and breast density do not influence sensitivity. Mammographic features, mass density, and thickness of the spicules in architectural distortions do influence.
doi:10.1007/s10278-012-9550-y
PMCID: PMC3649063  PMID: 23131867
Breast neoplasm; Cancer detection; Computer-assisted detection
11.  Cancer Screening with Digital Mammography for Women at Average Risk for Breast Cancer, Magnetic Resonance Imaging (MRI) for Women at High Risk 
Executive Summary
Objective
The purpose of this review is to determine the effectiveness of 2 separate modalities, digital mammography (DM) and magnetic resonance imaging (MRI), relative to film mammography (FM), in the screening of women asymptomatic for breast cancer. A third analysis assesses the effectiveness and safety of the combination of MRI plus mammography (MRI plus FM) in screening of women at high risk. An economic analysis was also conducted.
Research Questions
How does the sensitivity and specificity of DM compare to FM?
How does the sensitivity and specificity of MRI compare to FM?
How do the recall rates compare among these screening modalities, and what effect might this have on radiation exposure? What are the risks associated with radiation exposure?
How does the sensitivity and specificity of the combination of MRI plus FM compare to either MRI or FM alone?
What are the economic considerations?
Clinical Need
The effectiveness of FM with respect to breast cancer mortality in the screening of asymptomatic average- risk women over the age of 50 has been established. However, based on a Medical Advisory Secretariat review completed in March 2006, screening is not recommended for women between the ages of 40 and 49 years. Guidelines published by the Canadian Task Force on Preventive Care recommend mammography screening every 1 to 2 years for women aged 50 years and over, hence, the inclusion of such women in organized breast cancer screening programs. In addition to the uncertainty of the effectiveness of mammography screening from the age of 40 years, there is concern over the risks associated with mammographic screening for the 10 years between the ages of 40 and 49 years.
The lack of effectiveness of mammography screening starting at the age of 40 years (with respect to breast cancer mortality) is based on the assumption that the ability to detect cancer decreases with increased breast tissue density. As breast density is highest in the premenopausal years (approximately 23% of postmenopausal and 53% of premenopausal women having at least 50% of the breast occupied by high density), mammography screening is not promoted in Canada nor in many other countries for women under the age of 50 at average risk for breast cancer. It is important to note, however, that screening of premenopausal women (i.e., younger than 50 years of age) at high risk for breast cancer by virtue of a family history of cancer or a known genetic predisposition (e.g., having tested positive for the breast cancer genes BRCA1 and/or BRCA2) is appropriate. Thus, this review will assess the effectiveness of breast cancer screening with modalities other than film mammography, specifically DM and MRI, for both pre/perimenopausal and postmenopausal age groups.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined whereas mortality is decreasing, though at a slower rate. The observed decreases in mortality rates may be attributable to screening, in addition to advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the Surveillance, Epidemiology and End Results (better known as SEER) cancer registry in the United States, indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20 year period, from 2.7 to 25 per 100,000.
There is a 4-fold lower incidence of breast cancer in the 40 to 49 year age group than in the 50 to 69 year age group (approximately 140 per 100,000 versus 500 per 100,000 women, respectively). The sensitivity of FM is also lower among younger women (approximately 75%) than for women aged over 50 years (approximately 85%). Specificity is approximately 80% for younger women versus 90% for women over 50 years. The increased density of breast tissue in younger women is likely responsible for the decreased accuracy of FM.
Treatment options for breast cancer vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy and/or radiotherapy. Surgery is the first-line intervention for biopsy-confirmed tumors. The subsequent use of radiation, chemotherapy or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is considered a noninvasive tumour.
Women at high risk for breast cancer are defined as genetic carriers of the more commonly known breast cancer genes (BRCA1, BRCA2 TP53), first degree relatives of carriers, women with varying degrees of high risk family histories, and/or women with greater than 20% lifetime risk for breast cancer based on existing risk models. Genetic carriers for this disease, primarily women with BRCA1 or BRCA2 mutations, have a lifetime probability of approximately 85% of developing breast cancer. Preventive options for these women include surgical interventions such as prophylactic mastectomy and/or oophorectomy, i.e., removal of the breasts and/or ovaries. Therefore, it is important to evaluate the benefits and risks of different screening modalities, to identify additional options for these women.
This Medical Advisory Secretariat review is the second of 2 parts on breast cancer screening, and concentrates on the evaluation of both DM and MRI relative to FM, the standard of care. Part I of this review (March 2006) addressed the effectiveness of screening mammography in 40 to 49 year old average-risk women. The overall objective of the present review is to determine the optimal screening modality based on the evidence.
Evidence Review Strategy
The Medical Advisory Secretariat followed its standard procedures and searched the following electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment database. The subject headings and keywords searched included breast cancer, breast neoplasms, mass screening, digital mammography, magnetic resonance imaging. The detailed search strategies can be viewed in Appendix 1.
Included in this review are articles specific to screening and do not include evidence on diagnostic mammography. The search was further restricted to English-language articles published between January 1996 and April 2006. Excluded were case reports, comments, editorials, nonsystematic reviews, and letters.
Digital Mammography: In total, 224 articles specific to DM screening were identified. These were examined against the inclusion/exclusion criteria described below, resulting in the selection and review of 5 health technology assessments (HTAs) (plus 1 update) and 4 articles specific to screening with DM.
Magnetic Resonance Imaging: In total, 193 articles specific to MRI were identified. These were examined against the inclusion/exclusion criteria described below, resulting in the selection and review of 2 HTAs and 7 articles specific to screening with MRI.
The evaluation of the addition of FM to MRI in the screening of women at high risk for breast cancer was also conducted within the context of standard search procedures of the Medical Advisory Secretariat. as outlined above. The subject headings and keywords searched included the concepts of breast cancer, magnetic resonance imaging, mass screening, and high risk/predisposition to breast cancer. The search was further restricted to English-language articles published between September 2007 and January 15, 2010. Case reports, comments, editorials, nonsystematic reviews, and letters were not excluded.
MRI plus mammography: In total, 243 articles specific to MRI plus FM screening were identified. These were examined against the inclusion/exclusion criteria described below, resulting in the selection and review of 2 previous HTAs, and 1 systematic review of 11 paired design studies.
Inclusion Criteria
English-language articles, and English or French-language HTAs published from January 1996 to April 2006, inclusive.
Articles specific to screening of women with no personal history of breast cancer.
Studies in which DM or MRI were compared with FM, and where the specific outcomes of interest were reported.
Randomized controlled trials (RCTs) or paired studies only for assessment of DM.
Prospective, paired studies only for assessment of MRI.
Exclusion Criteria
Studies in which outcomes were not specific to those of interest in this report.
Studies in which women had been previously diagnosed with breast cancer.
Studies in which the intervention (DM or MRI) was not compared with FM.
Studies assessing DM with a sample size of less than 500.
Intervention
Digital mammography.
Magnetic resonance imaging.
Comparator
Screening with film mammography.
Outcomes of Interest
Breast cancer mortality (although no studies were found with such long follow-up).
Sensitivity.
Specificity.
Recall rates.
Summary of Findings
Digital Mammography
There is moderate quality evidence that DM is significantly more sensitive than FM in the screening of asymptomatic women aged less than 50 years, those who are premenopausal or perimenopausal, and those with heterogeneously or extremely dense breast tissue (regardless of age).
It is not known what effect these differences in sensitivity will have on the more important effectiveness outcome measure of breast cancer mortality, as there was no evidence of such an assessment.
Other factors have been set out to promote DM, for example, issues of recall rates and reading and examination times. Our analysis did not show that recall rates were necessarily improved in DM, though examination times were lower than for FM. Other factors including storage and retrieval of screens were not the subject of this analysis.
Magnetic Resonance Imaging
There is moderate quality evidence that the sensitivity of MRI is significantly higher than that of FM in the screening of women at high risk for breast cancer based on genetic or familial factors, regardless of age.
Radiation Risk Review
Cancer Care Ontario conducted a review of the evidence on radiation risk in screening with mammography women at high risk for breast cancer. From this review of recent literature and risk assessment that considered the potential impact of screening mammography in cohorts of women who start screening at an earlier age or who are at increased risk of developing breast cancer due to genetic susceptibility, the following conclusions can be drawn:
For women over 50 years of age, the benefits of mammography greatly outweigh the risk of radiation-induced breast cancer irrespective of the level of a woman’s inherent breast cancer risk.
Annual mammography for women aged 30 – 39 years who carry a breast cancer susceptibility gene or who have a strong family breast cancer history (defined as a first degree relative diagnosed in their thirties) has a favourable benefit:risk ratio. Mammography is estimated to detect 16 to 18 breast cancer cases for every one induced by radiation (Table 1). Initiation of screening at age 35 for this same group would increase the benefit:risk ratio to an even more favourable level of 34-50 cases detected for each one potentially induced.
Mammography for women under 30 years of age has an unfavourable benefit:risk ratio due to the challenges of detecting cancer in younger breasts, the aggressiveness of cancers at this age, the potential for radiation susceptibility at younger ages and a greater cumulative radiation exposure.
Mammography when used in combination with MRI for women who carry a strong breast cancer susceptibility (e.g., BRCA1/2 carriers), which if begun at age 35 and continued for 35 years, may confer greatly improved benefit:risk ratios which were estimated to be about 220 to one.
While there is considerable uncertainty in the risk of radiation-induced breast cancer, the risk expressed in published studies is almost certainly conservative as the radiation dose absorbed by women receiving mammography recently has been substantially reduced by newer technology.
A CCO update of the mammography radiation risk literature for 2008 and 2009 gave rise to one article by Barrington de Gonzales et al. published in 2009 (Barrington de Gonzales et al., 2009, JNCI, vol. 101: 205-209). This article focuses on estimating the risk of radiation-induced breast cancer for mammographic screening of young women at high risk for breast cancer (with BRCA gene mutations). Based on an assumption of a 15% to 25% or less reduction in mortality from mammography in these high risk women, the authors conclude that such a reduction is not substantially greater than the risk of radiation-induced breast cancer mortality when screening before the age of 34 years. That is, there would be no net benefit from annual mammographic screening of BRCA mutation carriers at ages 25-29 years; the net benefit would be zero or small if screening occurs in 30-34 year olds, and there would be some net benefit at age 35 years or older.
The Addition of Mammography to Magnetic Resonance Imaging
The effects of the addition of FM to MRI screening of high risk women was also assessed, with inclusion and exclusion criteria as follows:
Inclusion Criteria
English-language articles and English or French-language HTAs published from September 2007 to January 15, 2010.
Articles specific to screening of women at high risk for breast cancer, regardless of the definition of high risk.
Studies in which accuracy data for the combination of MRI plus FM are available to be compared to that of MRI and FM alone.
RCTs or prospective, paired studies only.
Studies in which women were previously diagnosed with breast cancer were also included.
Exclusion Criteria
Studies in which outcomes were not specific to those of interest in this report.
Studies in which there was insufficient data on the accuracy of MRI plus FM.
Intervention
Both MRI and FM.
Comparators
Screening with MRI alone and FM alone.
Outcomes of Interest
Sensitivity.
Specificity.
Summary of Findings
Magnetic Resonance Imaging Plus Mammography
Moderate GRADE Level Evidence that the sensitivity of MRI plus mammography is significantly higher than that of MRI or FM alone, although the specificity remains either unchanged or decreases in the screening of women at high risk for breast cancer based on genetic/familial factors, regardless of age.
These studies include women at high risk defined as BRCA1/2 or TP53 carriers, first degree relatives of carriers, women with varying degrees of high risk family histories, and/or >20% lifetime risk based on existing risk models. This definition of high risk accounts for approximately 2% of the female adult population in Ontario.
PMCID: PMC3377503  PMID: 23074406
12.  Reliability and validity of needle biopsy evaluation of breast-abnormalities using the B-categorization – design and objectives of the Diagnosis Optimisation Study (DIOS) 
BMC Cancer  2007;7:100.
Background
The planned nationwide implementation of mammography screening 2007 in Germany will increase the occurrence of mammographically detected breast abnormalities. These abnormalities are normally evaluated by minimal invasive core biopsy. To minimize false positive and false negative histological findings, quality assurance of the pathological evaluation of the biopsies is essential. Various guidelines for quality assurance in breast cancer diagnosis recommend applying the B-classification for histopathological categorization. However, to date there are only few studies that reported results about reliability and validity of B-classification. Therefore, objectives of our study are to determine the inter- and intraobserver variability (reliability study) and construct and predictive validity (validity study) of core biopsy evaluation of breast abnormalities. This paper describes the design and objectives of the DIOS Study.
Methods/Design
All consecutive asymptomatic and symptomatic women with breast imaging abnormalities who are referred to the University Hospital of Halle for core breast biopsy over a period of 24 months are eligible. According to the sample size calculation we need 800 women for the study. All patients in the study population underwent clinical and radiological examination. Core biopsy is performed by stereotactic-, ultrasound- or magnetic resonance (MR) guided automated gun method or vacuum assisted method. The histopathologic agreement (intra- and interobserver) of pathologists and the histopathologic validity will be evaluated. Two reference standards are implemented, a reference pathologist and in case of suspicious or malignant findings the histopathologic result of excision biopsy. Furthermore, a self administrated questionnaire which contains questions about potential risk factors of breast cancer, is sent to the participants approximately two weeks after core biopsy. This enables us to run a case-control-analysis (woman with breast cancer histological verified after excision are defined as cases, woman without malignant breast lesions are defined as controls) to investigate the predictive values of various risk factors on breast cancer risk.
Conclusion
The analysis of reliability and validity of the histopathological evaluation of core biopsy specimens of breast abnormalities is intended to provide important information needed for a high quality in breast cancer diagnostic and for planning of treatment strategies.
doi:10.1186/1471-2407-7-100
PMCID: PMC1913923  PMID: 17570833
13.  Surgical outcomes of borderline breast lesions detected by needle biopsy in a breast screening program 
Background
The Australian Capital Territory and South East New South Wales branch of BreastScreen Australia (BreastScreen ACT&SENSW) performs over 20,000 screening mammograms annually. This study describes the outcome of surgical biopsies of the breast performed as a result of a borderline lesion being identified after screening mammography and subsequent workup.
A secondary aim was to identify any parameters, such as a family history of breast cancer, or radiological findings that may indicate which borderline lesions are likely to be upgraded to malignancy after surgery.
Methods
From a period of just over eight years, all patients of BreastScreen ACT&SENSW who were diagnosed with a borderline breast lesion were identified. These women had undergone needle biopsy in Breastscreen ACT&SENSW and either atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), atypical lobular hyperplasia (ALH), radial scar/complex sclerosing lesion, papillary lesion, mucocoele-like lesion (MLL) or lobular carcinoma in situ (LCIS) was found. Final outcomes for each type of borderline lesion after referral for surgical biopsy were recorded and analysed. Results of the surgical biopsy were compared to the type of needle biopsy and its result, radiological findings and family history status.
Results
Of the 94 surgical biopsies performed due to the presence of a borderline breast lesion, 20% showed benign pathology, 55% remained as borderline lesions, 17% showed non-invasive malignancy and 7% showed invasive malignancy. VALCS biopsy was the most common needle biopsy method used to identify the lesions in this study (76%). Malignant outcomes resulted from 24% of the surgical biopsies, with the most common malignant lesion being non-comedo ductal carcinoma in situ (DCIS). The most common borderline lesion for which women underwent surgical biopsy was ADH (38%). Of these women, 22% were confirmed as ADH on surgical biopsy and 47% with a malignancy.
Conclusions
Further research is required to determine whether characteristics of the mammographic lesion (particularly calcification patterns), the area targeted for biopsy and number of core samples retrieved, can indicate a closer correlation with eventual pathology. This study identified no findings in the diagnostic assessment that could exclude women with borderline lesions from surgical biopsy.
doi:10.1186/1477-7819-8-78
PMCID: PMC2945347  PMID: 20822548
14.  Correlation of Mammographic Calcifications with HER-2/neu Overexpression in Primary Breast Carcinomas 
Journal of Digital Imaging  2008;21(2):170-176.
HER-2/neu is a valuable therapeutic and prognostic marker in primary breast carcinomas. The aim of this study was to evaluate the association between mammographic calcifications and HER-2/neu overexpression in primary breast carcinomas and assess its clinical perspective. A retrospective study of 152 preoperative mammograms in patients with breast carcinoma was performed. Expression of HER-2/neu was determined by immunohistochemical staining on 152 tissues that comprised specimens of 11 ductal carcinoma in situ (DCIS) and 141 primary invasive carcinomas. Mammographic calcifications were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS), fourth edition. Calcifications were found in 73 (48.0%) out of 152 patients by mammography finding. Calcifications were more common in carcinomas with HER-2/neu overexpression (45:73, 61.6%) than in those without HER-2/neu overexpression (28:79, 35.4%; P = 0.001). Of the 73 carcinomas with calcifications on mammography, mass with spiculated margin as an associated finding of calcifications was more significantly frequent in carcinomas with HER-2/neu overexpression (15 of 45, 33.3%) than in those without HER-2/neu overexpression (2 of 28, 7.1%; P = 0.036). Fine linear morphology was more common in carcinomas with HER-2/neu overexpression (15:45, 33.3%) when compared with those without HER-2/neu overexpression (2:28, 7.1%; P = 0.036). Clustered distribution of calcifications was more common in carcinomas with HER-2/neu overexpression (26:45, 57.8%) compared with carcinomas without HER-2/neu overexpression (6:28, 21.4%; P = 0.048). Mammographic calcifications are correlated with HER-2/neu overexpression in primary breast carcinomas. Calcifications detected during screening mammography are not only of diagnostic value but of use in determining therapeutic options and prognosis.
doi:10.1007/s10278-008-9105-4
PMCID: PMC3043864  PMID: 18256879
Breast neoplasms; mammography; calcification; HER-2/neu
15.  Absence of Residual Microcalcifications in Atypical Ductal Hyperplasia Diagnosed via Stereotactic Vacuum-Assisted Breast Biopsy: Is Surgical Excision Obviated? 
Journal of Breast Cancer  2014;17(3):265-269.
Purpose
The purpose of our study was to evaluate the underestimation rate of atypical ductal hyperplasia (ADH) on vacuum-assisted breast biopsy (VABB), and to examine the correlation between residual microcalcifications and the underestimation rate of ADH.
Methods
A retrospective study was performed on 27 women (mean age, 49.2±9.2 years) who underwent additional excision for ADH via VABB for microcalcifications observed by using mammography. The mammographic findings, histopathologic diagnosis of all VABB and surgical specimens, and association of malignancy with residual microcalcifications were evaluated. The underestimation rate of ADH was also calculated.
Results
Of the 27 women with microcalcifications, nine were upgraded to ductal carcinoma in situ (DCIS); thus, the underestimation rate was 33.3% (9/27). There was no difference in age (p=0.40) and extent of microcalcifications (p=0.10) when comparing benign and malignant cases. Six of 17 patients (35.3%) with remaining calcifications after VABB were upgraded to DCIS, and three of 10 patients (30%) with no residual calcifications after VABB were upgraded (p=1.00).
Conclusion
The underestimation rate of ADH on VABB was 33.3%. Furthermore, 30% of patients with no remaining calcifications were upgraded to DCIS. Therefore, we conclude that all ADH cases diagnosed via VABB should be excised regardless of the presence of residual microcalcifications.
doi:10.4048/jbc.2014.17.3.265
PMCID: PMC4197357  PMID: 25320625
Breast; Calcinosis; Large-core needle biopsy; Mammography; Segmental mastectomy
16.  The Role of Sonography in Patients with Breast Cancer Presenting as an Axillary Mass 
Korean Journal of Radiology  2002;3(3):189-193.
Objective
To compare sonography and mammography in terms of their diagnostic value in breast cancer cases which initially presented as an axillary mass without a palpable mass or other clinical symptoms.
Materials and Methods
Seven patients with enlarged axillary lymph nodes who first presented with no evidence of palpable breast lesions and who underwent both mammography and sonography were enrolled in this study. In six of the seven, the presence of metastatic adenocarcinoma was confirmed preoperatively by axillary needle aspiration biopsy; in four, subsequent sonographically-guided breast core biopsy performed after careful examination of the primary site indicated that primary breast cancer was present. In each case, the radiologic findings were evaluated by both breast sonography and mammography.
Results
Breast lesions were detected mammographically in four of seven cases (57%); in three of the four, the lesion presented as a mass, and in one as microcalcification. In three of these four detected cases, fatty or scattered fibroglandular breast parenchyma was present; in one, the parenchyma was dense. In the three cases in which lesions were not detected, mammography revealed the presence of heterogeneously dense parenchyma. Breast sonography showed that lesions were present in six of seven cases (86%); in the remaining patient, malignant microcalcification was detected at mammography. Final pathologic examination indicated that all breast lesions except one, which was a ductal carcinoma in situ, with microinvasion, were infiltrating ductal carcinomas whose size ranged from microscopic to greater than 3 cm. At the time of this study, all seven patients were alive and well, having been disease free for up to 61 months after surgery.
Conclusion
In women with a palpable axillary mass confirmed as metastatic adenocarcinoma, breast sonography may be a valuable adjunct to mammography.
doi:10.3348/kjr.2002.3.3.189
PMCID: PMC2713883  PMID: 12271164
Breast neoplasms, diagnosis; Breast neoplasms, radiography; Breast neoplasms, US
17.  Computerized Detection of Breast Tissue Asymmetry Depicted on Bilateral Mammograms: A Preliminary Study of Breast Risk Stratification 
Academic radiology  2010;17(10):1234-1241.
Rationale and Objective
Assessment of the breast tissue pattern asymmetry depicted on bilateral mammograms is routinely used by radiologists when reading and interpreting mammograms. The purpose of this study is to develop an automated scheme to detect breast tissue asymmetry depicted on bilateral mammograms and use the computed asymmetric features to predict the likelihood (or the risk) of women having or developing breast abnormalities or cancer.
Materials and Methods
A testing dataset was selected from a large and diverse full-field digital mammography image database, which includes 100 randomly selected negative cases (not recalled during the screening) and 100 positive cases for having or developing breast abnormalities or cancer. Among these positive cases 40 were recalled (biopsy) due to suspicious findings in which 8 were determined as high-risk with the lesions surgically removed and the remaining were proven to be benign, and 60 cases were acquired from examinations that were interpreted as negative (without dominant masses or micro-calcifications) but the cancers were detected 6 to 18 months later. A computerized scheme was developed to detect asymmetry of mammographic tissue density represented by the related feature differences computed from bilateral images. Initially, each of 20 features was tested to classify between the positive and the negative cases. To further improve the classification performance, a genetic algorithm (GA) was applied to select a set of optimal features and build an artificial neural network (ANN). The leave-one-case-out validation method was used to evaluate the ANN classification performance.
Results
Using a single feature, the maximum classification performance level measured by the area under the receiver operating characteristic curve (AUC), was 0.681±0.038. Using the GA-optimized ANN, the classification performance level increased to an AUC = 0.754±0.024. At 90% specificity, the ANN classifier yielded 42% sensitivity in which 42 positive cases were correctly identified. Among them, 30 were the “prior” examinations of the cancer cases and 12 were recalled benign cases, which represent 50% and 30% sensitivity levels in these two sub-groups, respectively.
Conclusions
This study demonstrated that using the computerized detected feature differences related to the bilateral mammographic breast tissue asymmetry, an automated scheme is able to classify a set of testing cases into the two groups of positive or negative of having or developing breast abnormalities and/or cancer. Hence, further development and optimization of this automated method may eventually help radiologists identify a fraction of women at high-risk of developing breast cancer and ultimately detect cancer at an early stage.
doi:10.1016/j.acra.2010.05.016
PMCID: PMC2939253  PMID: 20619697
Breast cancer; Mammography; Mammographic breast tissue asymmetry; Computer-aided detection (CAD); Risk assessment
18.  A Comprehensive Methodology for Determining the Most Informative Mammographic Features 
Journal of Digital Imaging  2013;26(5):941-947.
This study aims to determine the most informative mammographic features for breast cancer diagnosis using mutual information (MI) analysis. Our Health Insurance Portability and Accountability Act-approved database consists of 44,397 consecutive structured mammography reports for 20,375 patients collected from 2005 to 2008. The reports include demographic risk factors (age, family and personal history of breast cancer, and use of hormone therapy) and mammographic features from the Breast Imaging Reporting and Data System lexicon. We calculated MI using Shannon’s entropy measure for each feature with respect to the outcome (benign/malignant using a cancer registry match as reference standard). In order to evaluate the validity of the MI rankings of features, we trained and tested naïve Bayes classifiers on the feature with tenfold cross-validation, and measured the predictive ability using area under the ROC curve (AUC). We used a bootstrapping approach to assess the distributional properties of our estimates, and the DeLong method to compare AUC. Based on MI, we found that mass margins and mass shape were the most informative features for breast cancer diagnosis. Calcification morphology, mass density, and calcification distribution provided predictive information for distinguishing benign and malignant breast findings. Breast composition, associated findings, and special cases provided little information in this task. We also found that the rankings of mammographic features with MI and AUC were generally consistent. MI analysis provides a framework to determine the value of different mammographic features in the pursuit of optimal (i.e., accurate and efficient) breast cancer diagnosis.
doi:10.1007/s10278-013-9588-5
PMCID: PMC3782597  PMID: 23503987
Breast cancer; Mammography; BI-RADS; Decision support; Informatics; Mutual information
19.  MRI of the Breast for the Detection and Assessment of the Size of Ductal Carcinoma in Situ 
Korean Journal of Radiology  2007;8(1):32-39.
Objective
The aim of the study was to compare the accuracy of magnetic resonance imaging (MRI) and mammography for the detection and assessment of the size of ductal carcinoma in situ (DCIS).
Materials and Methods
The preoperative contrast-enhanced MRI and mammography were analyzed in respect of the detection and assessment of the size of DCIS in 72 patients (age range: 30-67 years, mean age: 47 years). The MRI and mammographic measurements were compared with the histopathologic size with using the Pearson's correlation coefficients and the Mann-Whitney u test. We evaluated whether the breast density, the tumor nuclear grade, the presence of comedo necrosis and microinvasion influenced the MRI and mammographic size estimates by using the chi-square test.
Results
Of the 72 DCIS lesions, 68 (94%) were detected by MRI and 62 (86%) were detected by mammography. Overall, the Pearson's correlation of the size between MRI and histopathology was 0.786 versus 0.633 between mammography and histopathology (p < 0.001). MRI underestimated the size by more than 1 cm (including false negative examination) in 12 patients (17%), was accurate in 52 patients (72%) and overestimated the size by more than 1 cm in eight patients (11%) whereas mammography underestimated the size in 25 patients (35%), was accurate in 31 patients (43%) and overestimated the size in 16 patients (22%). The MRI, but not the mammography, showed significant correlation for the assessment of the size of tumor in noncomedo DCIS (p < 0.001 vs p = 0.060). The assessment of tumor size by MRI was affected by the nuclear grade (p = 0.008) and the presence of comedo necrosis (p = 0.029), but not by the breast density (p = 0.747) or microinvasion (p = 0.093).
Conclusion
MRI was more accurate for the detection and assessment of the size of DCIS than mammography.
doi:10.3348/kjr.2007.8.1.32
PMCID: PMC2626696  PMID: 17277561
Breast neoplasms; Magnetic resonance (MR), comparative studies; Mammography
20.  False Positive Marks on Unsuspicious Screening Mammography with Computer-Aided Detection 
Journal of Digital Imaging  2011;24(5):772-777.
The contribution of computer-aided detection (CAD) systems as an interpretive aid in screening mammography can be hampered by a high rate of false positive detections. Specificity, false positive rate, and ease of dismissing false positive marks from two CAD systems are retrospectively evaluated. One hundred screening mammographic studies with a BI-RADS assessment code of 1 or 2 and at least 2-year normal mammographic follow-up were retrospectively reviewed using two CAD systems. Breast density, CAD marks, and radiologist's ease of dismissing false positive marks were recorded. Specificities from the two CAD versions considering all marks were 23% and 15% (p value = 0.07); mass marks, 35% and 17% (p value < 0.01); and calcification marks 62% and 75% (p value = 0.01). The two CAD versions did not differ regarding mean and median marks per case for all marks (2.3, 2.0 and 2.3, 2.0, p value = 0.65) or mass marks (1.6, 1.0 and 1.8, 2.0, p value = 0.15), but differed for calcification marks (0.8, 0 and 0.5, 0, p value < 0.01). Slightly higher specificity and fewer marks per case observed in dense breasts did not reach statistical significance. The reviewing radiologist classified most marks from both CAD systems (84% and 88%) as very easy/easy to dismiss. The two CAD versions had small differences in specificity and false positive marks. Differences, although not statistically significant, in specificities and false positive rates between dense and non-dense breasts warrant further research. Most false positive marks are easily dismissed and should not affect clinical performance.
doi:10.1007/s10278-011-9389-7
PMCID: PMC3180536  PMID: 21547517
Screening mammograms; Computer-aided detection (CAD); False positive marks; Specificity; Breast density
21.  Magnetic resonance imaging in size assessment of invasive breast carcinoma with an extensive intraductal component 
Background
Breast-conserving treatment of invasive breast carcinoma with an extensive intraductal component (EIC) is associated with DCIS-involved surgical margins and therefore it has an increased recurrence rate. EIC is a non-palpable lesion of which the size is frequently underestimated on mammography. This study was undertaken to evaluate the accuracy of MRI in size assessment of breast cancer with EIC.
Methods
23 patients were identified and the mammographic (n = 21) and MR (n = 23) images were re-reviewed by a senior radiologist. Size on MR images was compared with histopathological tumour extent.
Results
The correlation of radiological size with histopathological size was r = 0.20 in mammography (p = 0.39) compared to r = 0.65 in MRI (p < 0.01). Mammography underestimated histopathological tumour size in 62%. MR images over- or underestimated tumour size in 22% and 30% of the cases, respectively. In poorly differentiated EIC, MRI adequately estimated the extent more often compared to moderately differentiated EIC (60% versus 25%, respectively).
Conclusion
Size assessment of MRI imaging was more accurate compared to mammography. This was predominantly true for poorly differentiated EIC.
doi:10.1186/1471-2342-9-5
PMCID: PMC2674416  PMID: 19351404
22.  Bilateral Mammographic Density Asymmetry and Breast Cancer Risk: A Preliminary Assessment 
European journal of radiology  2012;81(11):3222-3228.
To improve efficacy of breast cancer screening and prevention programs, it requires a risk assessment model with high discriminatory power. This study aimed to assess classification performance of using computed bilateral mammographic density asymmetry to predict risk of individual women developing breast cancer in near-term. The database includes 451 cases with multiple screening mammography examinations. The first (baseline) examinations of all case were interpreted negative. In the next sequential examinations, 187 cases developed cancer or surgically excised high-risk lesions, 155 remained negative (not-recalled), and 109 were recalled benign cases. From each of two bilateral cranio-caudal view images acquired from the baseline examination, we computed two features of average pixel value and local pixel value fluctuation. We then computed mean and difference of each feature computed from two images. When applying the computed features and other two risk factors (woman’s age and subjectively rated mammographic density) to predict risk of cancer development, areas under receiver operating characteristic curves (AUC) were computed to evaluate the discriminatory/classification performance. The AUCs are 0.633±0.030, 0.535±0.036, 0.567±0.031, and 0.719±0.027 when using woman’s age, subjectively rated, computed mean and asymmetry of mammographic density, to classify between two groups of cancer-verified and negative cases, respectively. When using an equal-weighted fusion method to combine woman’s age and computed density asymmetry, AUC increased to 0.761±0.025 (p<0.05). The study demonstrated that bilateral mammographic density asymmetry could be a significantly stronger risk factor associated to the risk of women developing breast cancer in near-term than woman’s age and assessed mean mammographic density.
doi:10.1016/j.ejrad.2012.04.018
PMCID: PMC3430819  PMID: 22579527
Breast cancer risk assessment; Full-field digital mammography; Mammographic density; Risk model
23.  Diagnostic utility of combined ultrasonography and mammography in the evaluation of women with mammographically dense breasts 
Journal of Ultrasound  2007;10(3):143-151.
Purpose
To assess the diagnostic utility and additional cost of combined breast ultrasonography and mammography in the evaluation of asymptomatic women with mammographically dense breasts.
Materials and methods
Of 5108 asymptomatic women, who underwent mammography, 1754 had dense breasts (BI-RADS 3 or 4) and negative mammographic outcome. They were divided in 4 subgroups according to their age (<40 yrs; 40–49 yrs; 50–59 yrs; >59 yrs). Breast ultrasonography was performed immediately after mammography. Lesions detected at ultrasonography were examined cytologically/histologically. Mammograms from women, who were diagnosed carcinoma at ultrasonography, were reviewed by an external radiologist. Costs per diagnosed carcinoma and per examined woman were calculated on the basis of current regional charges.
Results
Mammographies (5108) were performed, 67 cancers were detected (cancer detection rate 13.1‰): mammography identified 55 carcinomas and ultrasonography performed in women with dense breasts identified 12 cancers (17.9% of all cancers detected, overall cancer detection rate 6.8‰). Ultrasonography identified a benign condition in 1567 out of 1754 women (89.3%) (in 925 absence of focal lesions; 438 simple cysts; 56 ductal ectasia; 148 benign solid lesions); 97 complex cysts, 52 lesions that could not be differentiated as liquid or solid lesions, and 38 solid lesions suspicious for malignancy in the remaining 187 out of 1754 patients (10.7%). Cytology/histology confirmed carcinoma in 12 women (overall biopsy rate 26.2‰, benign biopsy rate 19.4‰). The additional costs were: € 6,123.45 per detected cancer, € 41.89 per examined woman.
Conclusion
Breast ultrasonography immediately after mammography in women with dense breasts is useful to avoid diagnostic delays and inconvenient medico-legal implications even though this procedure involves increased costs.
doi:10.1016/j.jus.2007.05.001
PMCID: PMC3478707  PMID: 23396266
Breast ultrasonography; Breast lesion; Breast cancer
24.  Breast vibro-acoustography: initial experience in benign lesions 
BMC Medical Imaging  2014;14(1):40.
Background
Vibro-acoustography (VA) is a newly developed imaging technology that is based on low-frequency vibrations induced in the object by the radiation force of ultrasound. VA is sensitive to the dynamic characteristics of tissue. Here, we evaluate the performance of VA in identifying benign lesions and compare the results to those of mammography.
Methods
An integrated mammography-VA system designed for in vivo breast imaging was tested on a group of female volunteers, age ≥ 18 years, with suspected breast lesions based on clinical examination. A set of VA scans was acquired after each corresponding mammography. Most lesions were classified as benign based on their histological results. However, in 4 cases, initial diagnosis based on clinical imaging determined that the lesions were cysts. These cysts were aspirated with needle aspiration and disappeared completely under direct ultrasound visualization. Therefore, no biopsies were performed on these cases and lesions were classified as benign based on clinical findings per clinical standards. To define the VA characteristics of benign breast masses, we adopted the features that are normally attributed to such masses in mammography. In a blinded assessment, three radiologists evaluated the VA images independently. The diagnostic accuracy of VA for detection of benign lesions was assessed by comparing the reviewers’ evaluations with clinical data.
Results
Out of a total 29 benign lesions in the group, the reviewers were able to locate all lesions on VA images and mammography, 100% with (95% confidence interval (CI): 88% to 100%). Two reviewers were also able to correctly classify 83% (95% CI: 65% to 92%), and the third reviewer 86% (95% CI: 65% to 95%) of lesions, as benign on VA images and 86% (95% CI: 69% to 95%) on mammography.
Conclusions
The results suggest that the mammographic characteristics of benign lesion may also be used to identify such lesions in VA. Furthermore, the results show the ability of VA to detect benign breast abnormalities with a performance comparable to mammography. Therefore, the VA technology has the potential to be utilized as a complementary tool for breast imaging applications. Additional studies are needed to compare the capabilities of VA and traditional ultrasound imaging.
doi:10.1186/s12880-014-0040-1
PMCID: PMC4304615  PMID: 25547172
Breast neoplasms; Breast ultrasonography; Mammography; Vibro-acoustography; Benign breast lesion
25.  Breast cancer imaging: Mammography among women of up to 45 years 
Polish Journal of Radiology  2010;75(1):37-42.
Summary
Background:
Among women under the age of 40, screening mammography examinations are not performed routinely. An ultrasonography scan is considered to be a basic breast imaging examination among younger women. The purpose of this study was to analyze mammography images, as well as to evaluate the usefulness and role of mammography in breast cancer diagnostic processes in women of up to 45 years, based on own experience.
Material/Methods:
A retrospective analysis of mammography images, including 144 cases of breast cancer diagnosed in the group of 140 women of 45 years of age. All the patients underwent pre-treatment mammography and surgery procedure. The images were evaluated in accordance to BIRADS criteria. Lesions detectable in mammography were grouped as follows: • spiculated mass; • non-microcalcified oval/round mass; • microcalcified mass (regardless of shape); • microcalcifications; • architectural distortion; • breast tissue asymmetry.
Results:
The most common mammographic symptom was solid tumor (41%), followed by microcalcified tumors (20.8%). Clusters of microcalcifications constituted 17.4% of mammography findings. In 4.9% of mammography scans, examination did not reveal any pathological lesions.
Conclusions:
Breast cancer mammograms of women aged up to 45 years do not differ from diagnostic pictures of breast cancer in older women.
The diagnostic appearance of breast cancer in 1/3 of the patients involved microcalcifications detectable only on mammograms.
All the women with suspicion of breast cancer should have their mammography examinations performed, irrespective of ultrasonography scans.
PMCID: PMC3389859  PMID: 22802759
breast cancer; mammography; young women; microcalcifications

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