Role of MRI in screening women at high risk for breast cancer

Breast cancer is diagnosed in over one million women worldwide every year. Until breast cancer can be prevented, early detection offers the best chance for cure. Mammographic screening is an effective method for early detection in average-risk women. However, the sensitivity of mammography is decreased in women at high risk for breast cancer. Because of its high sensitivity, multiple investigators have studied the potential role of MRI in screening women at high risk. In the past few years, results from eight major clinical trials exploring breast MRI as a screening tool have been published. Combined, the studies included 4271 patients and found 144 breast cancers detected by MRI, for an overall cancer yield of 3%. The sensitivity of MRI ranged from 71% to 100% across the studies. Although its reported specificity was variable, the call-back rates and risk of benign biopsies were within acceptable limits. In general, patients who underwent breast MRI screening had a 10% risk of being called back, and a 5% risk of having a benign biopsy. This work reviews the literature and current practices and recommendations for MRI as a screening tool for high-risk women.     

Contrast-enhanced mammography: past,present, and future

Contrast-enhanced mammography (CEM) combines conventional mammography with iodinated contrast material to improve cancer detection. CEM has comparable performance to breast MRI without the added cost or time of conventional MRI protocols. Thus, this technique may be useful for indications previously reserved for MRI, such as problem-solving, determining disease extent in patients with newly diagnosed cancer, monitoring response to neoadjuvant therapy, evaluating the posttreatment breast for residual or recurrent disease, and potentially screening in women at intermediate- or high-risk for breast cancer. This article will provide a comprehensive overview on the past, present, and future of CEM, including its evolving role in the diagnostic and screening settings.     

The use of magnetic resonance imaging in breast cancer screening

Screening mammography is a powerful tool for reducing breast cancer mortality. Mammography can often detect clinically occult, early-stage breast cancer that is amenable to successful treatment. However, mammography is not a perfect test and has lower sensitivity in young women and in those with dense breasts. Magnetic resonance imaging (MRI) has been shown to depict breast cancers that are occult to other forms of detection, including mammography. This has generated interest in the use of MRI for breast cancer screening. Although preliminary studies in highly selected populations show promise for the potential efficacy of breast cancer screening with MRI, there are many questions that should be addressed before this technique is offered to the general population.     

Comparison of screening CEDM and MRI for women at increased risk for breast cancer: A pilot study

ObjectivesContrast enhanced digital mammography (CEDM) is a new breast imaging technology increasingly used in the diagnostic setting but its utility in the pure screening setting has not been reported. The goal of this pilot study is to prospectively compare screening CEDM to breast MRI in women with an increased risk for breast cancer.MethodsIn this IRB-approved HIPAA-compliant study, 318 women at increased breast cancer risk were consented (December 2012–May 2015) to undergo CEDM in addition to their scheduled MRI. CEDM was performed within 30 days of screening MRI. CEDM was interpreted blinded to MRI. The reference standard was defined as a combination of pathology and 2-year imaging follow-up.ResultsData from 307/318 patients were evaluable. Three cancers (two invasive cancers, one ductal carcinoma in situ) were detected at first round screening: MRI detected all three and CEDM detected the two invasive cancers. None of the three cancers was seen on the low energy mammograms which are comparable to conventional mammography. At 2 year imaging follow up, there were 5 additional screen detected cancers and no palpable cancers. The positive predictive value 3 (PPV₃) for CEDM was 15% (2/13, 95% CI: 2–45%) and 14% for MRI (3/21, 95% CI: 3–36%). The specificity of CEDM and MRI were 94.7% and 94.1% respectively.ConclusionsBoth CEDM and MRI detected additional cancers not seen on conventional mammography, primarily invasive cancers. Our pilot data suggest that CEDM could be valuable as a supplemental imaging exam for women at increased risk for breast cancer who do not meet the criteria for MRI or for whom access to MRI is limited. Validation in larger multi institutional trials is warranted.     

Wertigkeit der Mamma-MRT als Ergänzung zu Mammographie und Sonographie bei Patientinnen mit erhöhtem Mammakarzinomrisiko

PURPOSE: The aim of this study is to give an overview on early detection of breast cancer in patients with an increased risk of breast cancer. Sensitivities and diagnostic accuracies of breast MRI, mammography and ultrasound were compared. MATERIAL AND METHODS: A systematic literature search of the past 3 years was performed. Studies which compared breast imaging modalities and used image-guided biopsy results as standard of reference were included. Patients included had to have had an increased lifetime risk for breast cancer (>15%). RESULTS: Regarding sensitivity and diagnostic accuracy, breast MRI performed best in comparison to the other modalities within this collective of patients. Sensitivities ranged from 71-100%, 0-78%, and 13-65%, for MRI, mammography, and ultrasound, respectively CONCLUSION: Breast MRI is a well established tool for screening in patients at high risk for developing breast cancer and is a valuable supplement to mammography and ultrasound within this selected cohort of patients.     

Localization of breast lesions shown only on MRI--a review for the UK Study of MRI Screening for Breast Cancer. Advisory Group of MARIBS

The UK study of screening for breast cancer compares mammography and dynamic contrast enhanced MRI of the breast in women at high genetic risk of developing cancer. Owing to the high sensitivity of MR in the breast, it is anticipated that some lesions will be visible only on MR. A key issue for the study is how to localize these lesions for histological verification and removal. This article reviews available methods and describes the current UK expertise and recent European developments. The use of MR compatible wires and markers has been explored in a phantom. The use of these markers in vivo is demonstrated in a case imaged by MR and mammography and further discussed. The susceptibility artefacts produced on MRI, and technical properties associated with these needles, wires and markers are discussed. The clinical pathway by which these lesions will be worked up for the study, and the quality control procedures for keeping the number of such biopsies to a minimum, are described. There is an urgent need for further centres in the UK to become proficient at removing lesions found only on MRI in support of this study and other breast MRI applications. The management of these lesions must be resolved in order to realize the full potential of MRI for screening for breast cancer in women at genetic risk, and for other diagnostic applications.     

Travel Burden to Breast MRI and Utilization: Are Risk and Sociodemographics Related?

PurposeMammography, unlike MRI, is relatively geographically accessible. Additional travel time is often required to access breast MRI. However, the amount of additional travel time and whether it varies on the basis of sociodemographic or breast cancer risk factors is unknown.MethodsThe investigators examined screening mammography and MRI between 2005 and 2012 in the Breast Cancer Surveillance Consortium by (1) travel time to the closest and actual mammography facility used and the difference between the two, (2) women’s breast cancer risk factors, and (3) sociodemographic characteristics. Logistic regression was used to examine the odds of traveling farther than the closest facility in relation to women’s characteristics.ResultsAmong 821,683 screening mammographic examinations, 76.6% occurred at the closest facility, compared with 51.9% of screening MRI studies (n = 3,687). The median differential travel time among women not using the closest facility for mammography was 14 min (interquartile range, 8-25 min) versus 20 min (interquartile range, 11-40 min) for breast MRI. Differential travel time for both imaging modalities did not vary notably by breast cancer risk factors but was significantly longer for nonurban residents. For non-Hispanic black compared with non-Hispanic white women, the adjusted odds of traveling farther than the closest facility were 9% lower for mammography (odds ratio, 0.91; 95% confidence interval, 0.87-0.95) but more than two times higher for MRI (odds ratio, 2.64; 95% confidence interval, 1.36-5.13).ConclusionsBreast cancer risk factors were not related to excess travel time for screening MRI, but sociodemographic factors were, suggesting the possibility that geographic distribution of advanced imaging may exacerbated disparities for some vulnerable populations.     

Associations in breast and colon cancer screening behavior in women

RATIONALE AND OBJECTIVES: Gender-based psychosocial factors appear to influence colorectal cancer (CRC) screening adherence. Given its near-universal acceptance by the public, screening mammography represents a potential "teachable moment" for educating patients about the risk of CRC. Accordingly, to better understand screening behaviors among women, data from the Behavioral Risk Factors Surveillance Survey (BRFSS) were analyzed to identify potential relationships that would allow interventions to enhance CRC screening. MATERIALS AND METHODS: Women 50 years and older who participated in the BRFSS 2001 survey were included in the analysis. Colorectal, breast, and cervical cancer screening adherence with American Cancer Society guidelines was determined. We identified the association between breast and cervical cancer screening adherence and general health and demographic characteristics with CRC screening adherence. RESULTS: After adjustment for sociodemographic factors in a multivariate analysis, women 60-69 years old (adjusted odds ratio [OR], 1.50; P < .01) and 70-79 years old (adjusted OR, 1.39; P < .01), having achieved at least some high school (adjusted OR, 1.62; P < .01) or college (adjusted OR, 2.11; P < .01) education, having health coverage (adjusted OR, 1.67; P < .01) or a personal physician (adjusted OR, 1.60; P < .01), and adherence to screening mammography (adjusted OR, 2.42; P < .01) and Pap smear (adjusted OR, 1.70; P < .01) were independently associated with an increased likelihood CRC screening adherence. Women in self-reported good general health were less likely to have adhered to CRC screening guidelines (adjusted OR, 0.79; P < .01). Current smokers were also less likely to have adhered to CRC screening guidelines than were women who never smoked or formerly smoked (adjusted OR, 0.76; P < .01). Participants who adhered to both mammography and Pap smear guidelines were significantly more likely to adhere to CRC screening (51.5% CRC screening adherence) compared with women who adhered to neither screening test (8.2% CRC screening adherence), with an adjusted OR of 5.67 (P < .001). Participants who adhered to both mammography and Pap smear guidelines were significantly more likely to adhere to CRC screening than were women who adhered to either screening test (38.0% CRC screening adherence) with an adjusted OR of 1.94 (P < .001). CONCLUSION: Women with up-to-date mammography and cervical cancer screening were more likely to be up-to-date with CRC screening. Regardless of the increased association between non-CRC-related cancer screening and CRC screening, rates of CRC screening utilization remained low in these otherwise compliant populations.     

致密型乳腺影像筛查技术及研究进展

乳腺密度反映乳腺X 线摄影上乳腺的组成成分,乳腺密度评估是乳腺X 线筛查的常规临床需求。致密型乳腺是乳腺癌的潜在危险因素之一,也是乳腺X 线筛查乳腺癌敏感性及特异性偏倚存在的主要因素之一。就数字乳腺X 线摄影、超声、乳腺断层融合摄影及MRI 对致密型乳腺的诊断效能及研究进展予以综述。     

MRI of occult breast carcinoma in a high-risk population

OBJECTIVE: The purpose of this study was to determine the frequency of cancer and the positive predictive value of biopsy in the first screening round of breast MRI in women at high risk of developing breast cancer. MATERIALS AND METHODS: Retrospective review was performed of the records of 367 consecutive women at high risk of developing breast cancer who had normal findings on mammography and their first breast MRI screening examination during a 2-year period. The frequency of recommending biopsy at the first screening MRI study and the biopsy results were reviewed. RESULTS: Biopsy was recommended in 64 women (17%). Biopsy revealed cancer that was occult on mammography and physical examination in 14 (24%) of 59 women who had biopsy and in 14 (4%) of 367 women who underwent breast MRI screening. Histologic findings in 14 women with cancer were ductal carcinoma in situ in eight (57%) and infiltrating carcinoma in six (43%). The median size of infiltrating carcinoma was 0.4 cm (range, 0.1-1.2 cm). Two patients had nodes that were positive for cancer. Biopsy revealed high-risk lesions (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, or radial scar) in 13 (4%) of 367 women and other benign findings in 32 (9%) of 367 women who had MRI screening. CONCLUSION: Among women at high risk of developing breast cancer, breast MRI led to a recommendation of biopsy in 17%. Cancer was found in 24% of women who underwent biopsy and in 4% of women who had breast MRI screening. More than half the MRI-detected cancers were ductal carcinoma in situ.     

Enhanced biological effectiveness of low energy X-rays and implications for the UK breast screening programme

Recent radiobiological studies have provided compelling evidence that the low energy X-rays as used in mammography are approximately four times--but possibly as much as six times--more effective in causing mutational damage than higher energy X-rays. Since current radiation risk estimates are based on the effects of high energy gamma radiation, this implies that the risks of radiation-induced breast cancers for mammography X-rays are underestimated by the same factor. The balance of risk and benefit for breast screening have been re-analysed for relative biological effectiveness (RBE) values between 1 and 6 for mammography X-rays. Also considered in the analysis is a change in the dose and dose-rate effectiveness factor (DDREF) from 2 to 1, women with larger than average breasts and implications for women with a family history of breast cancer. A potential increase in RBE to 6 and the adoption of a DDREF of unity does not have any impact on the breast screening programme for women aged 50-70 years screened on a 3 yearly basis. Situations for which breast screening is not justified due to the potential cancers induced relative to those detected (the detection-to-induction ratio (DIR)) are given for a range of RBE and DDREF values. It is concluded that great caution is needed if a programme of early regular screening with X-rays is to be used for women with a family history of breast cancer since DIR values are below 10 (the lowest value considered acceptable for women below 40 years) even for modest increases in the RBE for mammography X-rays.     

Tomosynthesis as a screening tool for breast cancer: A systematic review

BackgroundMammography is an important screening tool for reducing breast cancer mortality. Digital breast tomosynthesis (DBT) can potentially be integrated with mammography to aid in cancer detection.MethodUsing the PRISMA guidelines, a systematic review of current literature was conducted to identify issues relating to the use of tomosynthesis as a screening tool together with mammography.FindingsUsing tomosynthesis with digital mammography (DM) increases breast cancer detection, reduces recall rates and increases the positive predictive value of those cases recalled. Invasive cancer detection is significantly improved in tomosynthesis compared to mammography, and has improved success for women with heterogeneous or extremely dense breasts.ConclusionTomosynthesis reduces some limitations of mammography at the time of screening that until recently were most often addressed by ultrasound at later work-up. Tomosynthesis can potentially be adopted alongside mammography as a screening tool.     

Präoperatives Staging mit der Mamma-MRT: Pro und Kontra

In oncologic patients, staging of the disease extent is of paramount importance. Imaging studies are used to decide whether the patient is a surgical candidate; if this is the case, imaging is used for detailed planning of the surgical procedure itself. Even in patients with limited prognosis, the first priority is always to achieve clear margins. Due to the widespread use of screening mammography, breast cancers are among the few cancers that are almost always diagnosed in an operable stage and are operated on with curative intention. It is well established that magnetic resonance imaging (MRI) is far superior to mammography (with and without concomitant ultrasound) for mapping the local extent of breast cancer. Accordingly, there is good reason to suggest that a pre-operative breast MRI should be considered an integral part of breast conserving treatment. Still, it is only rarely used in clinical practice. Arguments against its use are: Its high costs, allegedly high number of false positive findings, lack of MR-guided breast biopsy facilities, lack of evidence from randomized prospective trials and, notably, fear of "overtreatment". This paper discusses the reservations against staging MRI and weighs them against its clinical advantages. The point is made that radiologists as well as breast surgeons should be aware of the possibility of overtreatment, i.e. unnecessary mastectomy for very small, "MRI-only" multicentric cancer foci that would indeed be sufficiently treated by radiation therapy. There is a clear need to adapt the guidelines established for treatment of mammography-diagnosed multicentric breast cancer to account for the additional use of MRI for staging. Until these guidelines are available, the management of additional, "MRI-only" diagnosed small multicentric cancer manifestations must be decided on wisely and with caution. MRI for staging may only be done in institutions that can also offer an MR-guided tissue sampling, preferably by MR-guided vacuum assisted biopsy, to provide pre-operative histological proof of lesions visible by breast MRI alone.     

Current Guidelines and Gaps in Breast Cancer Screening

Breast cancer is the most common nonskin cancer in women and the second leading cause of cancer death for women in the United States. Mammography screening is proven to significantly decrease breast cancer mortality, with a 40% or more reduction expected with annual use starting at age 40 for women of average risk. However, less than half of all eligible women have a mammogram annually. The elimination of cost sharing for screening made possible by the Affordable Care Act (2010) encouraged screening but mainly for those already insured. The United States Preventive Services Task Force 2009 guidelines recommended against screening those 40 to 49 years old and have left women over 74 years of age vulnerable to coverage loss. Other populations for whom significant gaps in risk information or screening use exist, including women of lower socioeconomic status, black women, men at higher than average risk of breast cancer, and sexual and gender minorities. Further work is needed to achieve higher rates of screening acceptance for all appropriate individuals so that the full mortality and treatment benefits of mammography screening can be realized.     

Pain during mammography: implications for breast screening programmes

Pain experienced during mammography can deter women from attending for breast cancer screening. Review of the current literature on pain experienced during mammography reveals three main areas of interest: reports of the frequency of pain, identification of predictors of pain and strategies for responding to pain. Implications of this literature for breast screening programmes include the need for appropriate measurements of pain during mammography that are valid for screening populations, a further understanding of organizational factors involved in screening programmes that may be predictors of pain and for the development of valid strategies for responding to pain within breast screening programmes.     

Breast MRI at 3.0 T in a high-risk familial breast cancer screening cohort: comparison with 1.5 T screening studies

Objectives

The sensitivity of X-ray mammography for the detection of breast malignancy in younger females is lower than that of breast MRI; consequently, guidelines recommend annual MRI for patients with a significantly elevated lifetime risk. The improved signal-to-noise ratio obtainable at 3.0 T should result in data superior to those obtainable at 1.5 T. However, breast imaging on higher field strength systems poses specific problems. As a result, caution has been urged in the implementation of breast MRI at 3.0 T. The aim of this study was to determine if it is appropriate to use 3.0 T MRI in the screening of patients by comparing the summary statistics achieved by this 3.0 T MRI programme against the published results of 1.5 T screening studies.

Methods

Over a 20-month period, 291 patients referred with an elevated familial risk of breast cancer were examined at 3.0 T. Resulting images were scored based on the Royal College of Radiologists Breast Group imaging classification. The reference standard was a combination of histology and follow-up imaging.

Results

Follow-up data were available in 267 patients. Analysis revealed positive and negative post-test probabilities of 28% [95% confidence intervals (CI); range, 10–60%] and 1% (95% CI; range, 0–2%), respectively. These results compared favourably against those of a recent meta-analysis [25.3% (95% CI; range, 18.4–33.8%) and 0.4% (95% CI; range, 0.2–0.9%), respectively].

Conclusion

Given the similar summary statistics between this work and the 1.5 T results, it would appear that screening of high-risk patients at 3.0 T has potential. Further studies should be undertaken to verify this result.It is believed that between 5% and 15% of all breast cancers can be attributed to hereditary risk due to genetic mutations [1]. A number of mutations have been identified, including BRCA1, BRCA2, TP53, PTEN, STK11 and CDH1 [2]. These mutations can result in a cumulative lifetime risk as high as 80% [1], compared with a risk of only 10% in the general female population [3]. Additionally, evidence suggests that in the breast malignancies that result from these genetic mutations a more aggressive phenotype is prevalent with higher grade, proliferation rates and negative hormone receptors [3].Management of patients deemed to have an increased hereditary risk of breast cancer usually follows one of two pathways: either a risk-reducing strategy such as prophylactic mastectomy, or active breast cancer surveillance. Regarding the latter, several prospective trials have reported that the sensitivity of X-ray mammography for the detection of breast malignancy in younger females is lower than that of MRI mammography [4-9]. Consequently, recent guidelines from the National Institute for Health and Clinical Excellence in the UK and the American Cancer Society have recommended annual MRI mammography for patients with a significantly elevated lifetime risk [10,11].While breast MRI has been demonstrated to have a higher sensitivity than X-ray mammography for this cohort of females, there is little if any consensus on the acquisition of breast MRI data. This lack of consensus is derived in part from the rapid pace of technical developments in MRI. Typically, technical advances in either software or hardware are rapidly adopted by those practitioners with appropriate access. A classic example has been the move from two-dimensional multislice non-contiguous dynamic acquisitions to three-dimensional (3D) total breast coverage dynamic acquisitions, which are now almost universally adopted. In recent years, 3.0 T scanners capable of breast imaging have become available. Theoretically, the improved signal-to-noise ratio (SNR) obtainable at 3.0 T should result in data superior to those obtainable at 1.5 T. The improved SNR level allows imaging protocols with greater spatial and/or temporal resolution than those achievable with 1.5 T systems. However, breast imaging on higher field strength systems also poses specific problems such as larger chemical shift, greater susceptibility artefacts, B1 inhomogeneities and increased T₁ relaxation times. Consequently, caution has been urged in the implementation of breast MRI at 3.0 T [12,13].The aim of this study was to determine whether it is appropriate to use 3.0 T breast MRI in the screening of patients at high familial risk of breast cancer by comparing the likelihood ratios and post-test probabilities achieved by this 3.0 T MRI breast screening programme against the published results of screening studies at 1.5 T.     

MRI vs. histologic measurement of breast cancer following chemotherapy: comparison with x-ray mammography and palpation

Twenty consecutive patients with breast cancer were evaluated following chemotherapy using MRI to assess the size of cancer residua and compare these data with subsequent histologic measurements of the viable tumor. This retrospective study also involved assessment of the preoperative size of the malignancy as determined by physical exam and x-ray mammogram. These values were later compared with the histology. The tumor size correlation coefficient between MRI and pathologic analysis was the highest, at 0.93. Physical exam and x-ray mammography (available for 17 patients) produced correlation coefficients of 0.72 and 0.63, respectively, compared to histologic measurement. The accuracy of MRI did not vary with the size of cancer residua. MRI is an accurate method for preoperative assessment of breast cancer residua following chemotherapy. J. Magn. Reson. Imaging 2001;13:868-875.     

Contrast-enhanced spectral mammography in patients referred from the breast cancer screening programme

Objectives

Feasibility studies have shown that contrast-enhanced spectral mammography (CESM) increases diagnostic accuracy of mammography. We studied diagnostic accuracy of CESM in patients referred from the breast cancer screening programme, who have a lower disease prevalence than previously published papers on CESM.

Methods

During 6 months, all women referred to our hospital were eligible for CESM. Two radiologists blinded to the final diagnosis provided BI-RADS classifications for conventional mammography and CESM. Statistical significance of differences between mammography and CESM was calculated using McNemar’s test. Receiver operating characteristic (ROC) curves were constructed for both imaging modalities.

Results

Of the 116 eligible women, 113 underwent CESM. CESM increased sensitivity to 100.0 % (+3.1 %), specificity to 87.7 % (+45.7 %), PPV to 76.2 % (+36.5 %) and NPV to 100.0 % (+2.9 %) as compared to mammography. Differences between conventional mammography and CESM were statistically significant (p?<?0.0001). A similar trend was observed in the ROC curve. For conventional mammography, AUC was 0.779. With CESM, AUC increased to 0.976 (p?<?0.0001). In addition, good agreement between tumour diameters measured using CESM, breast MRI and histopathology was observed.

Conclusion

CESM increases diagnostic performance of conventional mammography, even in lower prevalence patient populations such as referrals from breast cancer screening.

Key Points

? CESM is feasible in the workflow of referrals from routine breast screening. ? CESM is superior to mammography, even in low disease prevalence populations. ? CESM has an extremely high negative predictive value for breast cancer. ? CESM is comparable to MRI in assessment of breast cancer extent. ? CESM is comparable to histopathology in assessment of breast cancer extent.     

Perspektiven der digitalen Mammographieplattform

In Europe one out of every nine women suffers from breast cancer during her lifetime. Since the introduction of mammography screening programs more breast cancers are being diagnosed when they are still small and early stage cancers with a favourable prognosis. The introduction of digital mammography systems has led to a continuous reduction of breast cancer mortality especially in specific patient subgroups. Furthermore, the digital mammography platform enables the development of new, innovative breast imaging methods to increase sensitivity and decrease breast cancer mortality. This digital mammography platform includes digital breast tomosynthesis, digital contrast medium mammography and digital contrast medium breast tomosynthesis as well as fused data sets from digital mammography with ultrasound or MRI. The following article summarizes these new applications, describes the strengths of the digital platform and illustrates the potential advantages of an improved breast cancer diagnosis by digital mammography.