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1.  Beyond Mammography: New Frontiers in Breast Cancer Screening 
The American journal of medicine  2013;126(6):472-479.
Breast cancer screening remains a subject of intense and, at times, passionate debate. Mammography has long been the mainstay of breast cancer detection and is the only screening test proven to reduce mortality. Although it remains the gold standard of breast cancer screening, there is increasing awareness of subpopulations of women for whom mammography has reduced sensitivity. Mammography has also undergone increased scrutiny for false positives and excessive biopsies, which increase radiation dose, cost and patient anxiety. In response to these challenges, new technologies for breast cancer screening have been developed, including; low dose mammography; contrast enhanced mammography, tomosynthesis, automated whole breast ultrasound, molecular imaging and MRI. Here we examine some of the current controversies and promising new technologies that may improve detection of breast cancer both in the general population and in high-risk groups, such as women with dense breasts. We propose that optimal breast cancer screening will ultimately require a personalized approach based on metrics of cancer risk with selective application of specific screening technologies best suited to the individual’s age, risk, and breast density.
PMCID: PMC4010151  PMID: 23561631
2.  Multimodality Screening of High-Risk Women: A Prospective Cohort Study 
Journal of Clinical Oncology  2009;27(36):6124-6128.
Mammography has been established as the primary imaging screening method for breast cancer; however, the sensitivity of mammography is limited, especially in women with dense breast tissue. Given the limitations of mammography, interest has developed in alternative screening techniques. This interest has led to numerous studies reporting mammographically occult breast cancers detected on magnetic resonance imaging (MRI) or ultrasound. In addition, digital mammography was shown to be more sensitive than film mammography in selected populations. Our goal was to prospectively compare cancer detection of digital mammography (DM), whole-breast ultrasound (WBUS), and contrast-enhanced MRI in a high-risk screening population previously screened negative by film screen mammogram (FSM).
During a 2-year period, 609 asymptomatic high-risk women with nonactionable FSM examinations presented for a prospective multimodality screening consisting of DM, WBUS, and MRI. The FSM examinations were reinterpreted by study radiologists. Patients had benign or no suspicious findings on clinical examination. The cancer yield by modality was evaluated.
Twenty cancers were diagnosed in 18 patients (nine ductal carcinomas in situ and 11 invasive breast cancers). The overall cancer yield on a per-patient basis was 3.0% (18 of 609 patients). The cancer yield by modality was 1.0% for FSM (six of 597 women), 1.2% for DM (seven of 569 women), 0.53% for WBUS (three of 567 women), and 2.1% for MRI (12 of 571 women). Of the 20 cancers detected, some were only detected on one imaging modality (FSM, n = 1; DM, n = 3; WBUS, n = 1; and MRI, n = 8).
The addition of MRI to mammography in the high-risk group has the greatest potential to detect additional mammographically occult cancers. The incremental cancer yield of WBUS and DM is much less.
PMCID: PMC2793033  PMID: 19884532
3.  Evaluating the correlation between mammography and MRI for screening women with increased breast cancer risk 
Academic radiology  2009;16(11):1323-1328.
Rationale and Objectives
Breast magnetic resonance imaging (MRI) is increasingly being added to mammography for screening asymptomatic women at increased risk of breast cancer. Because the direction and extent of correlation between mammography and MRI could potentially result in over- or under-estimation of the diagnostic gain related to using MRI as an adjunct to mammographic screening, we performed an analysis to evaluate the extent of correlation between mammography and MRI.
Materials and Methods
We reviewed the published literature to identify multimodality breast cancer screening studies reporting the sensitivity of mammography and MRI, alone and in combination, for breast cancer diagnosis. After calculating the expected sensitivity of combined mammography and MRI under conditions of test independence (no correlation), we compared the calculated and observed sensitivities for combined mammography and MRI. We then calculated correlation coefficients for mammography and MRI.
Seven studies of multimodality screening in women at increased risk of developing breast cancer were included for analysis. Of these studies, the correlation between film mammography and MRI was positive in three studies, negative in two studies, and not identified in two studies. The calculated correlation coefficients ranged from -0.38 to 0.18. In 6 of 7 studies, the 95% confidence interval for the correlation coefficient included 0.0, indicating no significant correlation.
Evidence from published trials of multimodality breast cancer screening identified no statistically significant correlation between film mammography and MRI. Using both tests for breast cancer screening is likely to improve the early detection of breast cancer in women at increased risk.
PMCID: PMC2763935  PMID: 19632865
Mammography; MRI; screening; technology assessment
4.  Cost-effectiveness of MRI for breast cancer screening in BRCA1/2 mutation carriers 
BMC Cancer  2013;13:339.
Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting.
We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis.
The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY.
The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness.
PMCID: PMC3711845  PMID: 23837641
Breast cancer; BRCA; MRI; Cost-effectiveness; Screening
5.  Cancer Screening with Digital Mammography for Women at Average Risk for Breast Cancer, Magnetic Resonance Imaging (MRI) for Women at High Risk 
Executive Summary
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.
Digital mammography.
Magnetic resonance imaging.
Screening with film mammography.
Outcomes of Interest
Breast cancer mortality (although no studies were found with such long follow-up).
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.
Both MRI and FM.
Screening with MRI alone and FM alone.
Outcomes of Interest
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
6.  Prospective screening study of 0.5 Tesla dedicated magnetic resonance imaging for the detection of breast cancer in young, high-risk women 
BMC Women's Health  2006;6:10.
Evidence-based screening guidelines are needed for women under 40 with a family history of breast cancer, a BRCA1 or BRCA2 mutation, or other risk factors. An accurate assessment of breast cancer risk is required to balance the benefits and risks of surveillance, yet published studies have used narrow risk assessment schemata for enrollment. Breast density limits the sensitivity of film-screen mammography but is not thought to pose a limitation to MRI, however the utility of MRI surveillance has not been specifically examined before in women with dense breasts. Also, all MRI surveillance studies yet reported have used high strength magnets that may not be practical for dedicated imaging in many breast centers. Medium strength 0.5 Tesla MRI may provide an alternative economic option for surveillance.
We conducted a prospective, nonrandomized pilot study of 30 women age 25–49 years with dense breasts evaluating the addition of 0.5 Tesla MRI to conventional screening. All participants had a high quantitative breast cancer risk, defined as ≥ 3.5% over the next 5 years per the Gail or BRCAPRO models, and/or a known BRCA1 or BRCA2 germline mutation.
The average age at enrollment was 41.4 years and the average 5-year risk was 4.8%. Twenty-two subjects had BIRADS category 1 or 2 breast MRIs (negative or probably benign), whereas no category 4 or 5 MRIs (possibly or probably malignant) were observed. Eight subjects had BIRADS 3 results, identifying lesions that were "probably benign", yet prompting further evaluation. One of these subjects was diagnosed with a stage T1aN0M0 invasive ductal carcinoma, and later determined to be a BRCA1 mutation carrier.
Using medium-strength MRI we were able to detect 1 early breast tumor that was mammographically undetectable among 30 young high-risk women with dense breasts. These results support the concept that breast MRI can enhance surveillance for young high-risk women with dense breasts, and further suggest that a medium-strength instrument is sufficient for this application. For the first time, we demonstrate the use of quantitative breast cancer risk assessment via a combination of the Gail and BRCAPRO models for enrollment in a screening trial.
PMCID: PMC1553433  PMID: 16800895
7.  Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts 
European Radiology  2009;20(3):734-742.
Mammography, the standard method of breast cancer screening, misses many cancers, especially in dense-breasted women. We compared the performance and diagnostic yield of mammography alone versus an automated whole breast ultrasound (AWBU) plus mammography in women with dense breasts and/or at elevated risk of breast cancer.
AWBU screening was tested in 4,419 women having routine mammography (Trial Registration: Identifier: NCT00649337). Cancers occurring during the study and subsequent 1-year follow-up were evaluated. Sensitivity, specificity and positive predictive value (PPV) of biopsy recommendation for mammography alone, AWBU and mammography with AWBU were calculated.
Breast cancer detection doubled from 23 to 46 in 6,425 studies using AWBU with mammography, resulting in an increase in diagnostic yield from 3.6 per 1,000 with mammography alone to 7.2 per 1,000 by adding AWBU. PPV for biopsy based on mammography findings was 39.0% and for AWBU 38.4%. The number of detected invasive cancers 10 mm or less in size tripled from 7 to 21 when AWBU findings were added to mammography.
AWBU resulted in significant cancer detection improvement compared with mammography alone. Additional detection and the smaller size of invasive cancers may justify this technology’s expense for women with dense breasts and/or at high risk for breast cancer.
PMCID: PMC2822222  PMID: 19727744
Mammography; Ultrasound; Breast cancer; Screening; Automated
8.  Breast imaging in the young: the role of magnetic resonance imaging in breast cancer screening, diagnosis and follow-up 
Journal of Thoracic Disease  2013;5(Suppl 1):S9-S18.
Diagnosis of breast cancer in young individuals (younger than 40 years old) poses a real challenge to breast radiologists because their breast tissue is often denser than the breast tissue of older women. Magnetic Resonance Imaging (MRI) may be particularly helpful in such situations. The American Cancer Society (ACS) recommended breast MRI screening as an adjunct to mammography for: BRCA mutation carriers and their first-degree relatives; women with a lifetime breast cancer risk ≥20% to 25%; women with a history of chest radiation between ages of 10 and 30 years; and women with predisposing genetic syndromes. Currently, breast MRI demonstrates a high sensitivity in the range of 93-100%. As many benign lesions also show enhancement or other atypical features on MRI, the primary weakness of contrast enhanced MRI remains in its low specificity, reported to be in the range of 37-97%. Breast MRI is helpful in demonstrating the true tumor size initially, as well as identifying residual tumor following the completion of neo-adjuvant therapy. In general, sensitivities ranging from 61% to 86% for detecting residual disease have been reported. The absence of enhancement virtually excludes a recurrence and the presence of enhancement is very specific for tumor even in the radiated breast. MRI is also the preferred modality for assessment of the breast after re- constructive surgery. The role of Magnetic Resonance Imaging (MRI) in breast diagnosis will continue to evolve as technology improves and clinical experience with new techniques expands.
PMCID: PMC3695543  PMID: 23819032
Breast cancer; young females; magnetic resonance imaging (MRI)
9.  Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population 
Breast magnetic resonance imaging (MRI) is a sensitive method of breast imaging virtually uninfluenced by breast density. Because of the improved sensitivity, breast MRI is increasingly being used for detection of breast cancer among high risk young women. However, the specificity of breast MRI is variable and costs are high. The purpose of this study was to determine if breast MRI is a cost-effective approach for the detection of breast cancer among young women at high risk.
A Markov model was created to compare annual breast cancer screening over 25 years with either breast MRI or mammography among young women at high risk. Data from published studies provided probabilities for the model including sensitivity and specificity of each screening strategy. Costs were based on Medicare reimbursement rates for hospital and physician services while medication costs were obtained from the Federal Supply Scale. Utilities from the literature were applied to each health outcome in the model including a disutility for the temporary health state following breast biopsy for a false positive test result. All costs and benefits were discounted at 5% per year. The analysis was performed from the payer perspective with results reported in 2006 U.S. dollars. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters.
Breast MRI provided 14.1 discounted quality-adjusted life-years (QALYs) at a discounted cost of $18,167 while mammography provided 14.0 QALYs at a cost of $4,760 over 25 years of screening. The incremental cost-effectiveness ratio of breast MRI compared to mammography was $179,599/QALY. In univariate analysis, breast MRI screening became < $50,000/QALY when the cost of the MRI was < $315. In the probabilistic sensitivity analysis, MRI screening produced a net health benefit of -0.202 QALYs (95% central range: -0.767 QALYs to +0.439 QALYs) compared to mammography at a willingness-to-pay threshold of $50,000/QALY. Breast MRI screening was superior in 0%, < $50,000/QALY in 22%, > $50,000/QALY in 34%, and inferior in 44% of trials.
Although breast MRI may provide health benefits when compared to mammographic screening for some high risk women, it does not appear to be cost-effective even at willingness to pay thresholds above $120,000/QALY.
PMCID: PMC2630922  PMID: 19144138
10.  Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer 
British Journal of Cancer  2006;95(7):801-810.
Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1–7 individual annual screening events. Women aged 35–49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was £28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to £11 731 (CE MRI vs mammography) and £15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.
PMCID: PMC2360541  PMID: 17016484
cost-effectiveness analysis; breast MRI; screening; BRCA1 and BRCA2; breast cancer; high risk
11.  Detected, yet not Diagnosed – Breast Cancer Screening with MRI Mammography in High-Risk Women 
Breast Care  2012;7(3):236-239.
MRI has been demonstrated to be the most sensitive imaging method for detecting breast cancer in women at high risk, allowing depiction of cancers that are occult on mammography, ultrasound and clinical breast examination. This high sensitivity is tempered by imperfect specificity due to overlap in the features of benign and malignant lesions.
We present the case of a young BRCA2 mutation carrier whose breast cancer could have been diagnosed 2 years earlier; this is a rare case of a false-negative finding in MRI.
We discuss morphological, physiological and psychological reasons for underestimation of MRI sets, especially in young women.
We conclude that double reading in MR screening for breast cancer in high-risk women, as conducted for mammography screening, could be considered.
PMCID: PMC3409389  PMID: 22872799
Breast imaging; Familiar breast cancer; Double reading
12.  Successful oxytocin-assisted nipple aspiration in women at increased risk for breast cancer 
Familial Cancer  2010;9(3):321-325.
The high rate of interval malignancies urges for new screening methods for women at high risk for breast cancer. Nipple aspiration provides direct access to the breast tissue and its DNA, and therefore is a likely candidate, but clinical applications have been limited by the failure to obtain nipple aspiration fluid from most women. We performed oxytocin-assisted nipple aspiration in 90 women at increased risk for breast cancer based on family history or genetic test results (n = 63) and/or previous breast cancer (n = 34). Nipple fluid was obtained from 81/90 women (90%) and bilaterally in 77%. Mean discomfort rating was 0.6 (on a 0–10 scale), which was significantly lower than for mammography or MRI. These findings suggest that a new tool for biomarker detection in oxytocin-assisted nipple fluid of women at high risk for breast cancer is at hand.
PMCID: PMC2921501  PMID: 20443067
Nipple aspiration; Breast cancer; BRCA1; BRCA2; Screening; Early detection
13.  Using Clinical Factors and Mammographic Breast Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model 
Annals of internal medicine  2008;148(5):337-347.
Current models for assessing breast cancer risk are complex and do not include breast density, a strong risk factor for breast cancer that is routinely reported with mammography.
To develop and validate an easy-to-use breast cancer risk prediction model that includes breast density.
Empirical model based on Surveillance, Epidemiology, and End Results incidence, and relative hazards from a prospective cohort.
Screening mammography sites participating in the Breast Cancer Surveillance Consortium.
1 095 484 women undergoing mammography who had no previous diagnosis of breast cancer.
Self-reported age, race or ethnicity, family history of breast cancer, and history of breast biopsy. Community radiologists rated breast density by using 4 Breast Imaging Reporting and Data System categories.
During 5.3 years of follow-up, invasive breast cancer was diagnosed in 14 766 women. The breast density model was well calibrated overall (expected–observed ratio, 1.03 [95% CI, 0.99 to 1.06]) and in racial and ethnic subgroups. It had modest discriminatory accuracy (concordance index, 0.66 [CI, 0.65 to 0.67]). Women with low-density mammograms had 5-year risks less than 1.67% unless they had a family history of breast cancer and were older than age 65 years.
The model has only modest ability to discriminate between women who will develop breast cancer and those who will not.
A breast cancer prediction model that incorporates routinely reported measures of breast density can estimate 5-year risk for invasive breast cancer. Its accuracy needs to be further evaluated in independent populations before it can be recommended for clinical use.
PMCID: PMC2674327  PMID: 18316752
14.  Accuracy and Outcomes of Screening Mammography in Women With a Personal History of Early-Stage Breast Cancer 
Women with a personal history of breast cancer (PHBC) are at risk of developing another breast cancer and are recommended for screening mammography. Few high-quality data exist on screening performance in PHBC women.
To examine the accuracy and outcomes of mammography screening in PHBC women relative to screening of similar women without PHBC.
Design and Setting
Cohort of PHBC women, mammogram matched to non-PHBC women, screened through facilities (1996–2007) affiliated with the Breast Cancer Surveillance Consortium.
There were 58 870 screening mammograms in 19 078 women with a history of early-stage (in situ or stage I-II invasive) breast cancer and 58 870 matched (breast density, age group, mammography year, and registry) screening mammograms in 55 315 non-PHBC women.
Main Outcome Measures
Mammography accuracy based on final assessment, cancer detection rate, interval cancer rate, and stage at diagnosis.
Within 1 year after screening, 655 cancers were observed in PHBC women (499 invasive, 156 in situ) and 342 cancers (285 invasive, 57 in situ) in non-PHBC women. Screening accuracy and outcomes in PHBC relative to non-PHBC women were cancer rates of 10.5 per 1000 screens (95%CI, 9.7–11.3) vs 5.8 per 1000 screens (95%CI, 5.2–6.4), cancer detection rate of 6.8 per 1000 screens (95%CI, 6.2–7.5) vs 4.4 per 1000 screens (95% CI, 3.9–5.0), interval cancer rate of 3.6 per 1000 screens (95%CI, 3.2–4.1) vs 1.4 per 1000 screens (95% CI, 1.1–1.7), sensitivity 65.4% (95% CI, 61.5%–69.0%) vs 76.5% (95% CI, 71.7%–80.7%), specificity 98.3% (95% CI, 98.2%–98.4%) vs 99.0% (95% CI, 98.9%–99.1%), abnormal mammogram results in 2.3% (95% CI, 2.2%–2.5%) vs 1.4% (95% CI, 1.3%–1.5%) (all comparisons P <.001). Screening sensitivity in PHBC women was higher for detection of in situ cancer (78.7%;95% CI, 71.4%–84.5%) than invasive cancer (61.1%; 95% CI, 56.6%–65.4%), P<.001; lower in the initial 5 years (60.2%; 95% CI, 54.7%–65.5%) than after 5 years from first cancer (70.8%;95% CI, 65.4%–75.6%), P =.006; and was similar for detection of ipsilateral cancer (66.3%; 95% CI, 60.3%–71.8%) and contralateral cancer (66.1%; 95% CI, 60.9%–70.9%), P=.96. Screen-detected and interval cancers in women with and without PHBC were predominantly early stage.
Mammography screening in PHBC women detects early-stage second breast cancers but has lower sensitivity and higher interval cancer rate, despite more evaluation and higher underlying cancer rate, relative to that in non-PHBC women.
PMCID: PMC3799940  PMID: 21343578
15.  Long-term results of screening with magnetic resonance imaging in women with BRCA mutations 
British Journal of Cancer  2012;107(1):24-30.
The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study.
From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography.
In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28 previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three patients died of other causes. None of the 24 survivors has had a distant recurrence at a median follow-up of 8.4 years since diagnosis.
Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will detect the majority of breast cancers at a very early stage. The absence of distant recurrences of incident cancers to date is encouraging. However, longer follow-up is needed to confirm the safety of breast surveillance.
PMCID: PMC3389408  PMID: 22588560
breast cancer; BRCA1/2 mutation; magnetic resonance imaging; mammography; screening; sensitivity and specificity
16.  Randomized Controlled Trial on Effectiveness of Ultrasonography Screening for Breast Cancer in Women Aged 40–49 (J-START): Research Design 
In cancer screening, it is essential to undertake effective screening with appropriate methodology, which should be supported by evidence of a reduced mortality rate. At present, mammography is the only method for breast cancer screening with such evidence. However, mammography does not achieve sufficient accuracy in breasts with high density at ages below 50. Although ultrasonography achieves better accuracy in Breast Cancer detection even in dense breasts, the effectiveness has not been verified. We have planned a randomized controlled trial to assess the effectiveness of ultrasonography in women aged 40–49, with a design to study 50 000 women with mammography and ultrasonography (intervention group), and 50 000 controls with mammography only (control group). The participants are scheduled to take second round screening with the same modality 2 years on. The primary endpoints are sensitivity and specificity, and the secondary endpoint is the rate of advanced breast cancers.
PMCID: PMC3028987  PMID: 21131295
breast cancer screening; mammography; ultrasonography; randomized controlled trial
17.  Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study 
Mammographic breast density is one of the strongest known risk factors for breast cancer. We present a novel technique for estimating breast density based on 3D T1-weighted Magnetic Resonance Imaging (MRI) and evaluate its performance, including for breast cancer risk prediction, relative to two standard mammographic density-estimation methods.
The analyses were based on MRI (n = 655) and mammography (n = 607) images obtained in the course of the UK multicentre magnetic resonance imaging breast screening (MARIBS) study of asymptomatic women aged 31 to 49 years who were at high genetic risk of breast cancer. The MRI percent and absolute dense volumes were estimated using our novel algorithm (MRIBview) while mammographic percent and absolute dense area were estimated using the Cumulus thresholding algorithm and also using a 21-point Visual Assessment scale for one medio-lateral oblique image per woman. We assessed the relationships of the MRI and mammographic measures to one another, to standard anthropometric and hormonal factors, to BRCA1/2 genetic status, and to breast cancer risk (60 cases) using linear and Poisson regression.
MRI percent dense volume is well correlated with mammographic percent dense area (R = 0.76) but overall gives estimates 8.1 percentage points lower (P < 0.0001). Both show strong associations with established anthropometric and hormonal factors. Mammographic percent dense area, and to a lesser extent MRI percent dense volume were lower in BRCA1 carriers (P = 0.001, P = 0.010 respectively) but there was no association with BRCA2 carrier status. The study was underpowered to detect expected associations between percent density and breast cancer, but women with absolute MRI dense volume in the upper half of the distribution had double the risk of those in the lower half (P = 0.009).
The MRIBview estimates of volumetric breast density are highly correlated with mammographic dense area but are not equivalent measures; the MRI absolute dense volume shows potential as a predictor of breast cancer risk that merits further investigation.
PMCID: PMC2815542  PMID: 19903338
18.  Mammographic screening and mammographic patterns 
Breast Cancer Research : BCR  2000;2(4):247-251.
Mammography is an effective screening modality for the early detection of breast cancer. The reduction in breast cancer mortality is greater for women aged over 50 at screening than for women aged under 50. Mammography can also contribute to an understanding of the biology of breast cancer. Screening trials provide good evidence for the dedifferentiation of a cancer as it develops over time, and the age dependency of this dedifferentiation explains much of the age difference in the effectiveness of screening. Mammographic density is an important predictor of future breast cancer risk, and has potential as an early endpoint in breast cancer prevention trials. Mammographic density is also an important determinant of mammographic screening sensitivity.
PMCID: PMC138783  PMID: 11250716
dedifferentiation; mammography; mammographic density; screening sensitivity
19.  Technology as a force for improved diagnosis and treatment of breast disease 
Canadian Journal of Surgery  2010;53(4):268-277.
Increasing numbers of women are seeking evaluation of screen-detected breast abnormalities, and more women with breast cancer are living with the consequences of treatment. Improved technologies have helped to individualize diagnostic evaluation and treatment, improve efficacy and minimize morbidity. This article highlights some of these technologies. Superior imaging techniques have improved breast cancer screening and show promise for intraoperative surgical guidance and postoperative specimen evaluation. Digital mammography improves the sensitivity of mammography for women younger than 50 years with dense breasts, and tomosynthesis may improve specificity. Magnetic resonance imaging provides sensitive delineation of the extent of the disease and superior screening for women with a greater than 25% lifetime risk of breast cancer Minimally invasive techniques have been developed for the assessment of intraductal lesions, biopsy of imaging abnormalities, staging of the axilla and breast radiotherapy. Ductoscopy facilitates intraductal biopsy and localization of lesions for excision, sentinel lymph node biopsy is becoming standard for axillary staging, and intraoperative radiotherapy has the potential to reduce treatment time and morbidity. Three-dimensional imaging allows correlation of final histology with preoperative imaging for superior margin assessment. Related techniques show promise for translation to the intraoperative setting for surgical guidance. New classifications of breast cancers based on gene expression, rather than morphology, describe subtypes with different prognoses and treatment implications, and new targeted therapies are emerging. Genetic fingerprints that predict treatment response and outcomes are being developed to assign targeted treatments to individual patients likely to benefit. Surgeons play a vital role in the successful integration of new technologies into practice.
PMCID: PMC2912014  PMID: 20646402
20.  Detection of Breast Cancer with Addition of Annual Screening Ultrasound or a Single Screening MRI to Mammography in Women with Elevated Breast Cancer Risk 
Annual ultrasound (US) may detect small, node-negative breast cancers not seen on mammography (M). MRI may depict additional breast cancers beyond mammography and ultrasound (M+US).
Determine supplemental cancer detection yield of ultrasound and MRI in women at elevated risk for breast cancer.
Design, Setting, Participants
From April 2004 to February 2006, 2809 women at 21 sites with elevated cancer risk and dense breasts consented to three annual independent screens with mammography and ultrasound in randomized order. After 3 rounds of mammography and US screening, 703 women from 14 sites consented to a single MRI.
Main Outcome Measures
Cancer detection rate (yield), sensitivity, specificity, positive predictive value of biopsies performed (PPV3 – rate of malignancy among cases positive on screening, who actually underwent biopsy), interval cancer rate. The diagnosis of breast cancer was based on a biopsy showing in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma in the breast or axillary lymph nodes. Reference standard was defined as a combination of pathology and 12-month follow-up and was available for 2662 women (7473 M+US screens) and 612 MRI participants.
The 2662 patients underwent 7473 mammograms and US, with 110 women having 111 breast cancers detected, of which 33 were detected on mammography only, 32 on US only, 26 on both mammography and US, and 9 on MRI after mammography and US. Eleven were not detected by any imaging modality. Supplemental incidence-screening US identified 3.7 cancers per 1000 women-screens (95% CI 2.1 to 5.8, p<.001). Sensitivity, specificity, and PPV3 for M +US were 57/75 (0.76, 95% CI 0.65 to 0.85), 3987/4739 (0.84, 95% CI 0.83 to 0.85), and 55/339 (0.16, 95% CI 0.12 to 0.21); and for mammography alone 39/75 (0.52, 95% CI 0.40 to 0.64), 4325/4739 (0.91,95% 0.90 to 0.92), and 37/97 (0.38, 95% CI 0.28 to 0.49) (p<.001 all comparisons). Of 612 analyzable MRI participants, 16 (2.6%) had breast cancer diagnosed. Supplemental yield of MRI was 14.7 per 1000 (95% CI 3.5 to 25.9, p=.004). Sensitivity, specificity, and PPV3 for MRI+M+US were 16/16 (1.00, 95% CI 0.79 to 1.00), 390/596 (0.65, 95% CI 0.61 to 0.69), and 15/81 (0.19, 95% CI 0.11 to 0.29); and for M+US 7/16 (0.44, 95% CI 0.20 to 0.70, p=.004), 503/596 (0.84, 95% CI 0.81 to 0.87, p <.001), and 7/38 (0.18, 95% CI 0.08 to 0.34, p= .98) for M+US. Number of screens needed to detect one cancer was 127(95%CI 99 to 167) for mammography; 234(95%CI 173 to 345) for supplemental ultrasound, and 68 (95%CI 39 to 286) for MRI after negative M+US.
The addition of screening ultrasound or MRI to mammography in women at increased risk of breast cancer resulted in a higher cancer detection yield but also an increase in false positive findings.
PMCID: PMC3891886  PMID: 22474203
21.  Personalizing Mammography by Breast Density and Other Risk Factors for Breast Cancer: Analysis of Health Benefits and Cost-Effectiveness 
Annals of internal medicine  2011;155(1):10-20.
Current guidelines recommend mammography every 1 or 2 years starting at age 40 or 50 years, regardless of individual risk for breast cancer.
To estimate the cost-effectiveness of mammography by age, breast density, history of breast biopsy, family history of breast cancer, and screening interval.
Markov microsimulation model.
Data Sources
Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and the medical literature.
Target Population
U.S. women aged 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years with initial mammography at age 40 years and breast density of Breast Imaging Reporting and Data System (BI-RADS) categories 1 to 4.
Time Horizon
National health payer.
Mammography annually, biennially, or every 3 to 4 years or no mammography.
Outcome Measures
Costs per quality-adjusted life-year (QALY) gained and number of women screened over 10 years to prevent 1 death from breast cancer.
Results of Base-Case Analysis
Biennial mammography cost less than $100 000 per QALY gained for women aged 40 to 79 years with BI-RADS category 3 or 4 breast density or aged 50 to 69 years with category 2 density; women aged 60 to 79 years with category 1 density and either a family history of breast cancer or a previous breast biopsy; and all women aged 40 to 79 years with both a family history of breast cancer and a previous breast biopsy, regardless of breast density. Biennial mammography cost less than $50 000 per QALY gained for women aged 40 to 49 years with category 3 or 4 breast density and either a previous breast biopsy or a family history of breast cancer. Annual mammography was not cost-effective for any group, regardless of age or breast density.
Results of Sensitivity Analysis
Mammography is expensive if the disutility of false-positive mammography results and the costs of detecting nonprogressive and nonlethal invasive cancer are considered.
Results are not applicable to carriers of BRCA1 or BRCA2 mutations.
Mammography screening should be personalized on the basis of a woman’s age, breast density, history of breast biopsy, family history of breast cancer, and beliefs about the potential benefit and harms of screening.
Primary Funding Source
Eli Lilly, Da Costa Family Foundation for Research in Breast Cancer Prevention of the California Pacific Medical Center, and Breast Cancer Surveillance Consortium.
PMCID: PMC3759993  PMID: 21727289
22.  Breast MRI Use Uncommon among U.S. Women 
The goal of breast cancer screening is to reduce breast cancer mortality. Mammography is the standard screening method for detecting breast cancer early. Breast magnetic resonance imaging (MRI) is recommended to be used in conjunction with mammography for screening subsets of women at high risk for breast cancer. We offer the first study to provide national estimates of breast MRI use among women in the United States.
We analyzed data from women who responded to questions about having a breast MRI on the 2010 National Health Interview Survey. We assessed report of having a breast MRI and reasons for it by sociodemographic characteristics and access to health care and computed 5-year and lifetime breast cancer risk using the Gail model.
Among 11,222 women who responded, almost 5% reported ever having a breast MRI and 2% reported having an MRI within the 2 years preceding the survey. Less than half of the women who reported having a breast MRI were at increased risk. Approximately 60% of women reported having the breast MRI for diagnostic reasons. Women who ever had a breast MRI were more likely to be older, black, and insured and to report a usual source of health care compared to women who reported no MRI.
Breast MRI use may be underused or overused in certain subgroups of women.
As access to health care improves, the use of breast MRI and the appropriateness of its use for breast cancer detection will be important to monitor.
PMCID: PMC3538940  PMID: 23155135
23.  Screening of Breast Cancer – an Eternal Discussion Revisited? 
Breast Care  2010;5(2):119-120.
New recommendations on screening for breast cancer in the USA recently presented by the US Preventive Services Task Force (USPSTF) and the Society of Breast Imaging and American Council of Radiologists (ACR) provoke some concerns about the optimal screening strategy for breast cancer. USPSTF recommendations published in November 2009 do not recommend screening mammography in women younger than 50 years old because of high false-positive rates and low effects on mortality and vote against self examination of the breast because of lacking evidence for survival benefit from randomized trials. Nevertheless, the ACR guidelines published two months later strongly support the beginning of screening mammography by the age of 40.
We asked Dr. Kettritz whether the new recommendation from the USA might have impact on the clinical routine in Europe?
Oleg Gluz and Cornelia Liedtke
PMCID: PMC2931048  PMID: 21048828
24.  Physicians’ attitudes and behaviour toward screening mammography in women 40 to 49 years of age 
Canadian Family Physician  2012;58(9):e508-e513.
To determine family physicians’ attitudes and behaviour toward screening mammography, breast self-examination, and breast awareness in women aged 40 to 49 at average risk of breast cancer.
Cross-sectional survey.
Women’s College Hospital and Sunnybrook Health Sciences Centre, both in Toronto, Ont.
Family medicine residents, fellows, and staff physicians at 2 academic family practice health centres affiliated with the University of Toronto (n = 95).
Main outcome measures
Physicians’ answers to questions about offering screening mammography and promoting breast self-examination and breast awareness.
Fifty-two completed surveys were returned (response rate 55%). Less than half of all surveyed family physicians (46%) routinely offered screening mammography to women aged 40 to 49 who were at average risk of breast cancer. Although 40% of physicians did not think breast cancer screening was necessary for women aged 40 to 49, 62% indicated that they would offer screening if their patients requested it. Physicians’ reasons not to offer screening included no evidence of decreasing breast cancer deaths (63%), grade A recommendation to screen women starting at age 50 and not at age 40 (25%), and the harms of screening outweighing the benefits (19%). Physicians’ reasons to offer screening included patient request (55%), personal clinical practice experience or mentors’ recommendations (27%), and guideline recommendations (18%). Breast self-examination was not recommended by most physicians (74%), yet most encouraged women to practise breast awareness (81%).
Many women at average risk of breast cancer are not being offered the opportunity to discuss and initiate mammographic screening before 50 years of age. While breast-self examination is not recommended, most physicians promote breast awareness.
PMCID: PMC3440292  PMID: 22972742
25.  Magnetic resonance imaging for secondary assessment of breast density in a high-risk cohort 
Magnetic resonance imaging  2009;28(1):8-15.
A quantitative measure of three-dimensional breast density derived from noncontrast magnetic resonance imaging (MRI) was investigated in 35 women at high-risk for breast cancer. A semiautomatic segmentation tool was used to quantify the total volume of the breast and to separate volumes of fibroglandular and adipose tissue in noncontrast MRI data. The MRI density measure was defined as the ratio of breast fibroglandular volume over total volume of the breast. The overall correlation between MRI and mammographic density measures was R2=.67. However the MRI/mammography density correlation was higher in patients with lower breast density (R2=.73) than in patients with higher breast density (R2=.26). Women with mammographic density higher than 25% exhibited very different magnetic resonance density measures spread over a broad range of values. These results suggest that MRI may provide a volumetric measure more representative of breast composition than mammography, particularly in groups of women with dense breasts. Magnetic resonance imaging density could potentially be quantified and used for a better assessment of breast cancer risk in these populations.
PMCID: PMC4087111  PMID: 19631485
Volumetric breast density; Breast MRI; Fuzzy c-means; Segmentation; Breast cancer risk; Mammographic density; MR breast density

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