Published Ahead of Print on June 23, 2014 as 10.1200/JCO.2014.56.1514 The latest version is at http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2014.56.1514
JOURNAL OF CLINICAL ONCOLOGY
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Rethinking Breast Cancer Screening: Ultra FAST Breast Magnetic Resonance Imaging Elizabeth A. Morris, Memorial Sloan Kettering Cancer Center, New York, NY See accompanying article doi: 10.1200/JCO.2013.52.5386
Breast cancer screening is once again controversial. It is hard to miss headlines stating that mammography is an imperfect screening test,1 missing biologically aggressive cancers and picking up indolent cancers that do not need treatment. We, who have devoted our lives to fighting breast cancer, have long been aware of the limitations of mammography, especially in women with extremely dense breast tissue. Mammography, for all its limits, is still the only test proven to decrease mortality in multiple randomized controlled trials and through experience with population-based screening.2 Detecting small cancers on imaging before they are palpable improves survival, as well as treatment options.3 Yet, questions persist. Does the test pick up too much and still not enough; is it wrong too often? Perhaps relying on anatomic density, distortions, and secondary byproducts (calcifications) of cancer on mammograms is not enough; we need a better test. As with oncologic treatment, oncologic imaging these days relies more on functionality than anatomy. Screening for breast cancer needs to catch up to this paradigm to better image clinically significant malignant changes. The quest for improvement in sensitivity and specificity of breast cancer screening is precisely why new tests are being developed by the radiology community. Traditional two-dimensional digital mammography is being supplanted by three-dimensional digital breast tomosynthesis (DBT), and contrast-enhanced digital mammography (CEDM) is a test that images vascularity as well as anatomic abnormalities. Screening breast ultrasound is an increasingly requested supplemental test in women of all breast densities. Luckily, we have had the most sensitive test for breast cancer detection at our disposal for decades: breast magnetic resonance imaging (MRI). And it rarely misses invasive breast cancers. Breast MRI can tell us functionally how a lesion is behaving as the images reflect the tumor’s molecular/genetic characteristics.4 Breast MRI does not use radiation, cannot induce cancers, and is exceedingly safe even though it does require intravenous contrast. Unlike mammography, which generates images based on the density of tissue, MRI creates a “blood flow map,” detecting tumor neovascularity and peritumoral inflammation; this explains its high sensitivity. Therefore, unlike mammography, MRI relies on alterations that correlate with proliferation and possibly metastatic potential. As medical oncology moves into new therapies based on oncogenetics and greater understanding of cell biology, the evolution in imaging is similarly a function of our new understanding of tumor biology. Journal of Clinical Oncology, Vol 32, 2014
In the article that accompanies this editorial, Kuhl et al5 show that a rapid (ie, 3-minute) breast MRI is comparable to the accepted standard 21-minute study when screening for cancer. They pared down the imaging protocol to the bare basics (three dimensional maximum intensity projection [MIP] and first postcontrast subtracted T1-weighted image [FAST]), cutting out any nonessential sequences. Although this protocol is likely not appropriate for diagnostic studies, by doing this in the screening setting they achieved a high detection rate without a high false-positive rate, the hallmarks of a quality screening test. They report that 603 screening rounds in 443 asymptomatic women at intermediate to slightly increased risk of breast cancer and with negative mammograms yielded 11 breast cancers, including seven invasive cancers and four ductal carcinoma in situ (DCIS; 18.3 of 1,000). All were Tis or T1, N0, M0, and almost all were path or nuclear grade 2 or 3. Median tumor size was 8.4 mm, and no interval cancers were diagnosed. MIP images allowed quick detection of enhancement that was further evaluated on the FAST images. MIP analysis alone yielded a sensitivity and negative predictive value of 98.9%, which increased to 100% with the FAST images. These results are exciting for they show that an ultrafast MRI scan can detect all those cancers—invasive as well as DCIS—that mammography cannot. The benefits of a fast examination are obvious. Patient tolerance is improved, and there is great potential for cost savings, which is related to shorter scan time. Kuhl et al show us that we can chip away at the cost of MRI and possibly make screening breast MRI competitive with other imaging tests, including mammography and ultrasound. Breast density legislation is now present in many states in the United States. Women and their physicians are requesting supplemental screening above and beyond mammography.6 It has perplexed many of us in the breast imaging community how screening breast ultrasound appears to be accepted for supplemental screening whereas breast MRI is not. There is not a single study that shows ultrasound detects more cancer than MRI. In fact, studies show that a significant number of cancers are missed on screening ultrasound but are readily found with MRI.7 Importantly, false positives are much greater with screening ultrasound than with screening MRI. In fact the likelihood of finding a cancer at biopsy performed on the basis of ultrasound screening is less than 10%, whereas it is approximately 30% with MRI.8 A much higher percentage of biopsies from screening MRI turn out to be cancer. © 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on June 30, 2014. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
Copyright 2014 by American Society of Clinical Oncology
1
Editorial
False-positive rates are important in the choice of a screening test. With experience and training, it has been shown that the false-positive rate of MRI can be lower than mammography. Radiology societies such as the American College of Radiology, Society of Breast Imaging, and European Society of Breast Imaging have prioritized the education of radiologists interpreting breast MRI. In the United States, the American College of Radiology offers accreditation of sites and radiologists so that women and referring physicians can know that the quality of the MRI examination and interpretation is excellent. Currently, with further maturation of the technology and radiologist experience, MRI overcalls have diminished. Of course no technology is perfect, and not all cancers are detected on MRI. It is exceedingly rare for MRI to miss an invasive cancer as most are associated with neovascularity. Invasive lobular carcinoma that may not be highly vascularized may be missed (although the vast numbers of invasive lobular carcinomas are indeed detected). Furthermore, the invasive cancers that are detected on MRI are small and mostly node negative.9 Although it is impossible with our current knowledge to know which of these invasive cancers is biologically aggressive and potentially metastatic, most breast experts would err in favor of treatment. The type of cancer that MRI most often misses is DCIS, although it seems that most of these are also MRI detectable. MRI may not detect DCIS that presents as calcifications on mammography because the DCIS may not have associated vascularity. DCIS is controversial and has been targeted as one of the problems with mammography causing unnecessary treatment. Previous data from the Kuhl group10 have shown that MRI sensitivity for DCIS detection increases from 80% for low grade to 98% for high grade, whereas the sensitivity of mammography actually decreases as DCIS grade increases, dropping from 61% for low grade DCIS to 35% for high-grade DCIS without necrosis. An interesting theory is that MRI appears to pick up the more biologically relevant DCIS, whereas mammography is geared for detection of the less biologically relevant. It is interesting to postulate that the more biologically relevant in situ disease that has invasive potential and possibly metastatic potential is the disease detected by MRI. So, given the impressive ability to detect cancer not seen on mammography and ultrasound, why not use MRI for screening in all women? Is perceived patient discomfort with loud knocking noises and tight confines part of the cause? Although these complaints were true, the last decade has seen improvements with noise dampening techniques and wider bores that cause less claustrophobia. Improvements continue, but most MRI suites these days are not those of yore. Moreover, mammography is plagued with complaints about discomfort and pain as a result of compression, as well as the use of radiation. Sonography screening may be difficult to schedule and is time consuming and messy. Access to magnets may be the major reason why more women are not undergoing screening with MRI. Limited access yields limited use. MRI scanners are expensive; they are large and require space and special shielding. In some areas, the dearth of scanners restricts access for large numbers of women in need. Then there is the issue of cost. Cost-effectiveness analyses11 justify use in the highrisk population; however, considering current prices (dictated by MRI time), use in lower risk population are questioned. With limited access for many, high cost, and outdated perceptions of efficacy, breast MRI is used today only in high-risk populations12-16 where the cost benefit analysis makes sense (many countries, including the United States and the United Kingdom, recommend annual breast MRI as first-line 2
© 2014 by American Society of Clinical Oncology
screening along with mammography for the highest risk women17). However, the current study by Kuhl et al5 breaks down several barriers that would limit this examination to only high-risk women. With a FAST MRI examination available that is quick, competitive in price, and highly sensitive, perhaps screening recommendations should be rethought and possibly expanded so that more women could benefit. How will we ever know if screening with breast MRI affects survival? We will never have a randomized trial to look at the outcome of MRI screening— or for that matter, any of these newer techniques—as the technology is rapidly progressing and improving. Screening trials of this sort are relegated to the past. They are expensive and imperfect trials that can still incite controversy these days. No long-term outcome study exists to show that MRI detection of small cancers affects long-term survival. Recent evidence from a Dutch modeling study18 shows that survival can be improved for women with a family risk of breast cancer who undergo breast MRI screening. Other studies19 have shown that in high-risk women, MRI-detected cancers are more often node negative and that these are more frequently smaller than 1 cm. Although surrogate indicators, these strongly suggest that survival is improved with MRI screening. So where does this study leave us? First and foremost we need to embrace breast MRI screening, even if it is not performed as FAST MRI, and offer it to our patients who are currently eligible as it is inarguably the best available screening test. It is a disservice to our patients not to do this. Next, we need to support a prospective clinical trial to hopefully establish FAST MRI as a viable alternative to the standard MRI examination. On the basis of the Kuhl et al study,5 performed at a single institution, there is enough evidence to perform a multicenter trial comparing FAST MRI with standard MRI. Importantly, when designing this trial, expert readers should be recruited to validate the newer technique as inexperienced readers may overcall or undercall potential lesions, decreasing confidence in the test. Hopefully the results of this trial will allow more practices to start offering more FAST MRI. Also, we need to make the price of a FAST MRI competitive with other supplemental screening modalities. Insurers must recognize that FAST breast MRI is a competitively priced, highly sensitive test with high specificity. Ultrasound is a comforting test, but we need to recognize that compared with other available technology, it is not very good, with marked limitations in cancer detection and excessive false positives. We need to recognize that if additional screening is required, breast MRI should be the next test, not ultrasound. The decision makers in detecting, preventing, and treating breast cancer are the patient and her physician. They know that screening can save lives. The preponderance of evidence says so. The breast cancer death rate was virtually unchanged until the 1990s when regular mammography was introduced and mortality dropped by 30%. Despite this, too many women—mothers, sisters, daughters, and friends—are still dying of breast cancer, even when screened. We are not picking up some of the biologically relevant cancers with mammography. Another test that builds on the success of mammography and that relies more on tumor biology and functionality, not just anatomy, is called for. Abbreviated FAST breast MRI is a huge step forward in breast cancer screening and may pave the way for future tests based on functionality rather than anatomy, and with better patient access, such as contrast-enhanced digital mammography. FAST breast MRI, with its ability to detect early neovascularity, could potentially make a big impact on identifying biologically relevant cancers that are fatal and JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on June 30, 2014. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
Editorial
currently missed by screening. Data clearly demonstrates that FAST breast MRI could be the standard for breast cancer screening: it is safe, does not induce cancers, and can find more cancers than mammography. We can and must do a better job of linking women with the screening test that can save their lives. AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Miller AB, Wall C, Baines CJ, et al: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial. BMJ 348:g366, 2014 2. Taba´r L, Vitak B, Chen TH, et al: Swedish two-county trial: Impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 260:658-663, 2011 3. Kopans DB: Arguments against mammography screening continue to be based on faulty science. Oncologist 19:107-112, 2014 4. Morris EA: Diagnostic breast MR imaging: Current status and future directions. Magn Reson Imaging Clin N Am 18:57-74, 2010 5. Kuhl CK, Schrading S, Strobel K, et al: Abbreviated breast magnetic resonance imaging (MRI): First postcontrast subtracted images and maximumintensity projection—A novel approach to breast cancer screening with MRI. J Clin Oncol doi: 10.1200/JCO.2013.52.5386 6. Hooley RJ, Scoutt LM, Philpotts LE: Breast ultrasonography: State of the art. Radiology 268:642-659, 2013 7. Berg WA, Zhang Z, Lehrer D, et al: Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA 307:1394-1404, 2012 8. Berg WA, Blume JD, Cormack JB, et al: Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA 299:2151-2163, 2008
9. Kuhl C, Weigel S, Schrading S, et al: Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: The EVA trial. J Clin Oncol 28:1450-1457, 2010 10. Kuhl CK: Why do purely intraductal cancers enhance on breast MR images? Radiology 253:281-283, 2009 11. Feig S: Cost-effectiveness of mammography, MRI, and ultrasonography for breast cancer screening Radiol Clin North Am 48:879-891, 2010 12. Kriege M, Brekelmans CT, Boetes C, et al: Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351:427-437, 2004 13. Warner E, Plewes DB, Hill KA, et al: Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292:1317-1325, 2004 14. Leach MO, Boggis CR, Dixon AK, et al: Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: A prospective multicentre cohort study (MARIBS). Lancet 365: 1769-1778, 2005 15. Kuhl CK, Schrading S, Leutner CC, et al: Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23:8469-8476, 2005 16. Lehman CD, Blume JD, Weatherall P, et al: Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 103:1898-1905, 2005 17. Saslow D, Boetes C, Burke W, et al: American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57:75-89, 2007 18. Saadatmand S, Tilanus-Linthorst MM, Rutgers EJ, et al: Cost-effectiveness of screening women with familial risk for breast cancer with magnetic resonance imaging. J Natl Cancer Inst 105:1314-1321, 2013 19. Sardanelli F, Podo F, D’Agnolo G, et al: Multicenter comparative multimodality surveillance of women at genetic-familial high risk for breast cancer (HIBCRIT study): Interim results. Radiology 242:698-715, 2007
DOI: 10.1200/JCO.2014.56.1514; published online ahead of print at www.jco.org on June 23, 2014
■ ■ ■
www.jco.org
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on June 30, 2014. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
3
Editorial
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Rethinking Breast Cancer Screening: Ultra FAST Breast Magnetic Resonance Imaging The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Elizabeth A. Morris Honoraria: Bracco Diagnostics Consulting or Advisory Role: Genentech
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on June 30, 2014. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
JOURNAL OF CLINICAL ONCOLOGY
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D
I
T
O
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L
Rethinking Breast Cancer Screening: Ultra FAST Breast Magnetic Resonance Imaging Elizabeth A. Morris, Memorial Sloan Kettering Cancer Center, New York, NY See accompanying article doi: 10.1200/JCO.2013.52.5386
Breast cancer screening is once again controversial. It is hard to miss headlines stating that mammography is an imperfect screening test,1 missing biologically aggressive cancers and picking up indolent cancers that do not need treatment. We, who have devoted our lives to fighting breast cancer, have long been aware of the limitations of mammography, especially in women with extremely dense breast tissue. Mammography, for all its limits, is still the only test proven to decrease mortality in multiple randomized controlled trials and through experience with population-based screening.2 Detecting small cancers on imaging before they are palpable improves survival, as well as treatment options.3 Yet, questions persist. Does the test pick up too much and still not enough; is it wrong too often? Perhaps relying on anatomic density, distortions, and secondary byproducts (calcifications) of cancer on mammograms is not enough; we need a better test. As with oncologic treatment, oncologic imaging these days relies more on functionality than anatomy. Screening for breast cancer needs to catch up to this paradigm to better image clinically significant malignant changes. The quest for improvement in sensitivity and specificity of breast cancer screening is precisely why new tests are being developed by the radiology community. Traditional two-dimensional digital mammography is being supplanted by three-dimensional digital breast tomosynthesis (DBT), and contrast-enhanced digital mammography (CEDM) is a test that images vascularity as well as anatomic abnormalities. Screening breast ultrasound is an increasingly requested supplemental test in women of all breast densities. Luckily, we have had the most sensitive test for breast cancer detection at our disposal for decades: breast magnetic resonance imaging (MRI). And it rarely misses invasive breast cancers. Breast MRI can tell us functionally how a lesion is behaving as the images reflect the tumor’s molecular/genetic characteristics.4 Breast MRI does not use radiation, cannot induce cancers, and is exceedingly safe even though it does require intravenous contrast. Unlike mammography, which generates images based on the density of tissue, MRI creates a “blood flow map,” detecting tumor neovascularity and peritumoral inflammation; this explains its high sensitivity. Therefore, unlike mammography, MRI relies on alterations that correlate with proliferation and possibly metastatic potential. As medical oncology moves into new therapies based on oncogenetics and greater understanding of cell biology, the evolution in imaging is similarly a function of our new understanding of tumor biology. Journal of Clinical Oncology, Vol 32, 2014
In the article that accompanies this editorial, Kuhl et al5 show that a rapid (ie, 3-minute) breast MRI is comparable to the accepted standard 21-minute study when screening for cancer. They pared down the imaging protocol to the bare basics (three dimensional maximum intensity projection [MIP] and first postcontrast subtracted T1-weighted image [FAST]), cutting out any nonessential sequences. Although this protocol is likely not appropriate for diagnostic studies, by doing this in the screening setting they achieved a high detection rate without a high false-positive rate, the hallmarks of a quality screening test. They report that 603 screening rounds in 443 asymptomatic women at intermediate to slightly increased risk of breast cancer and with negative mammograms yielded 11 breast cancers, including seven invasive cancers and four ductal carcinoma in situ (DCIS; 18.3 of 1,000). All were Tis or T1, N0, M0, and almost all were path or nuclear grade 2 or 3. Median tumor size was 8.4 mm, and no interval cancers were diagnosed. MIP images allowed quick detection of enhancement that was further evaluated on the FAST images. MIP analysis alone yielded a sensitivity and negative predictive value of 98.9%, which increased to 100% with the FAST images. These results are exciting for they show that an ultrafast MRI scan can detect all those cancers—invasive as well as DCIS—that mammography cannot. The benefits of a fast examination are obvious. Patient tolerance is improved, and there is great potential for cost savings, which is related to shorter scan time. Kuhl et al show us that we can chip away at the cost of MRI and possibly make screening breast MRI competitive with other imaging tests, including mammography and ultrasound. Breast density legislation is now present in many states in the United States. Women and their physicians are requesting supplemental screening above and beyond mammography.6 It has perplexed many of us in the breast imaging community how screening breast ultrasound appears to be accepted for supplemental screening whereas breast MRI is not. There is not a single study that shows ultrasound detects more cancer than MRI. In fact, studies show that a significant number of cancers are missed on screening ultrasound but are readily found with MRI.7 Importantly, false positives are much greater with screening ultrasound than with screening MRI. In fact the likelihood of finding a cancer at biopsy performed on the basis of ultrasound screening is less than 10%, whereas it is approximately 30% with MRI.8 A much higher percentage of biopsies from screening MRI turn out to be cancer. © 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on June 30, 2014. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
Copyright 2014 by American Society of Clinical Oncology
1
Editorial
False-positive rates are important in the choice of a screening test. With experience and training, it has been shown that the false-positive rate of MRI can be lower than mammography. Radiology societies such as the American College of Radiology, Society of Breast Imaging, and European Society of Breast Imaging have prioritized the education of radiologists interpreting breast MRI. In the United States, the American College of Radiology offers accreditation of sites and radiologists so that women and referring physicians can know that the quality of the MRI examination and interpretation is excellent. Currently, with further maturation of the technology and radiologist experience, MRI overcalls have diminished. Of course no technology is perfect, and not all cancers are detected on MRI. It is exceedingly rare for MRI to miss an invasive cancer as most are associated with neovascularity. Invasive lobular carcinoma that may not be highly vascularized may be missed (although the vast numbers of invasive lobular carcinomas are indeed detected). Furthermore, the invasive cancers that are detected on MRI are small and mostly node negative.9 Although it is impossible with our current knowledge to know which of these invasive cancers is biologically aggressive and potentially metastatic, most breast experts would err in favor of treatment. The type of cancer that MRI most often misses is DCIS, although it seems that most of these are also MRI detectable. MRI may not detect DCIS that presents as calcifications on mammography because the DCIS may not have associated vascularity. DCIS is controversial and has been targeted as one of the problems with mammography causing unnecessary treatment. Previous data from the Kuhl group10 have shown that MRI sensitivity for DCIS detection increases from 80% for low grade to 98% for high grade, whereas the sensitivity of mammography actually decreases as DCIS grade increases, dropping from 61% for low grade DCIS to 35% for high-grade DCIS without necrosis. An interesting theory is that MRI appears to pick up the more biologically relevant DCIS, whereas mammography is geared for detection of the less biologically relevant. It is interesting to postulate that the more biologically relevant in situ disease that has invasive potential and possibly metastatic potential is the disease detected by MRI. So, given the impressive ability to detect cancer not seen on mammography and ultrasound, why not use MRI for screening in all women? Is perceived patient discomfort with loud knocking noises and tight confines part of the cause? Although these complaints were true, the last decade has seen improvements with noise dampening techniques and wider bores that cause less claustrophobia. Improvements continue, but most MRI suites these days are not those of yore. Moreover, mammography is plagued with complaints about discomfort and pain as a result of compression, as well as the use of radiation. Sonography screening may be difficult to schedule and is time consuming and messy. Access to magnets may be the major reason why more women are not undergoing screening with MRI. Limited access yields limited use. MRI scanners are expensive; they are large and require space and special shielding. In some areas, the dearth of scanners restricts access for large numbers of women in need. Then there is the issue of cost. Cost-effectiveness analyses11 justify use in the highrisk population; however, considering current prices (dictated by MRI time), use in lower risk population are questioned. With limited access for many, high cost, and outdated perceptions of efficacy, breast MRI is used today only in high-risk populations12-16 where the cost benefit analysis makes sense (many countries, including the United States and the United Kingdom, recommend annual breast MRI as first-line 2
© 2014 by American Society of Clinical Oncology
screening along with mammography for the highest risk women17). However, the current study by Kuhl et al5 breaks down several barriers that would limit this examination to only high-risk women. With a FAST MRI examination available that is quick, competitive in price, and highly sensitive, perhaps screening recommendations should be rethought and possibly expanded so that more women could benefit. How will we ever know if screening with breast MRI affects survival? We will never have a randomized trial to look at the outcome of MRI screening— or for that matter, any of these newer techniques—as the technology is rapidly progressing and improving. Screening trials of this sort are relegated to the past. They are expensive and imperfect trials that can still incite controversy these days. No long-term outcome study exists to show that MRI detection of small cancers affects long-term survival. Recent evidence from a Dutch modeling study18 shows that survival can be improved for women with a family risk of breast cancer who undergo breast MRI screening. Other studies19 have shown that in high-risk women, MRI-detected cancers are more often node negative and that these are more frequently smaller than 1 cm. Although surrogate indicators, these strongly suggest that survival is improved with MRI screening. So where does this study leave us? First and foremost we need to embrace breast MRI screening, even if it is not performed as FAST MRI, and offer it to our patients who are currently eligible as it is inarguably the best available screening test. It is a disservice to our patients not to do this. Next, we need to support a prospective clinical trial to hopefully establish FAST MRI as a viable alternative to the standard MRI examination. On the basis of the Kuhl et al study,5 performed at a single institution, there is enough evidence to perform a multicenter trial comparing FAST MRI with standard MRI. Importantly, when designing this trial, expert readers should be recruited to validate the newer technique as inexperienced readers may overcall or undercall potential lesions, decreasing confidence in the test. Hopefully the results of this trial will allow more practices to start offering more FAST MRI. Also, we need to make the price of a FAST MRI competitive with other supplemental screening modalities. Insurers must recognize that FAST breast MRI is a competitively priced, highly sensitive test with high specificity. Ultrasound is a comforting test, but we need to recognize that compared with other available technology, it is not very good, with marked limitations in cancer detection and excessive false positives. We need to recognize that if additional screening is required, breast MRI should be the next test, not ultrasound. The decision makers in detecting, preventing, and treating breast cancer are the patient and her physician. They know that screening can save lives. The preponderance of evidence says so. The breast cancer death rate was virtually unchanged until the 1990s when regular mammography was introduced and mortality dropped by 30%. Despite this, too many women—mothers, sisters, daughters, and friends—are still dying of breast cancer, even when screened. We are not picking up some of the biologically relevant cancers with mammography. Another test that builds on the success of mammography and that relies more on tumor biology and functionality, not just anatomy, is called for. Abbreviated FAST breast MRI is a huge step forward in breast cancer screening and may pave the way for future tests based on functionality rather than anatomy, and with better patient access, such as contrast-enhanced digital mammography. FAST breast MRI, with its ability to detect early neovascularity, could potentially make a big impact on identifying biologically relevant cancers that are fatal and JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on June 30, 2014. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
Editorial
currently missed by screening. Data clearly demonstrates that FAST breast MRI could be the standard for breast cancer screening: it is safe, does not induce cancers, and can find more cancers than mammography. We can and must do a better job of linking women with the screening test that can save their lives. AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. Miller AB, Wall C, Baines CJ, et al: Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: Randomised screening trial. BMJ 348:g366, 2014 2. Taba´r L, Vitak B, Chen TH, et al: Swedish two-county trial: Impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 260:658-663, 2011 3. Kopans DB: Arguments against mammography screening continue to be based on faulty science. Oncologist 19:107-112, 2014 4. Morris EA: Diagnostic breast MR imaging: Current status and future directions. Magn Reson Imaging Clin N Am 18:57-74, 2010 5. Kuhl CK, Schrading S, Strobel K, et al: Abbreviated breast magnetic resonance imaging (MRI): First postcontrast subtracted images and maximumintensity projection—A novel approach to breast cancer screening with MRI. J Clin Oncol doi: 10.1200/JCO.2013.52.5386 6. Hooley RJ, Scoutt LM, Philpotts LE: Breast ultrasonography: State of the art. Radiology 268:642-659, 2013 7. Berg WA, Zhang Z, Lehrer D, et al: Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA 307:1394-1404, 2012 8. Berg WA, Blume JD, Cormack JB, et al: Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA 299:2151-2163, 2008
9. Kuhl C, Weigel S, Schrading S, et al: Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: The EVA trial. J Clin Oncol 28:1450-1457, 2010 10. Kuhl CK: Why do purely intraductal cancers enhance on breast MR images? Radiology 253:281-283, 2009 11. Feig S: Cost-effectiveness of mammography, MRI, and ultrasonography for breast cancer screening Radiol Clin North Am 48:879-891, 2010 12. Kriege M, Brekelmans CT, Boetes C, et al: Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351:427-437, 2004 13. Warner E, Plewes DB, Hill KA, et al: Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292:1317-1325, 2004 14. Leach MO, Boggis CR, Dixon AK, et al: Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: A prospective multicentre cohort study (MARIBS). Lancet 365: 1769-1778, 2005 15. Kuhl CK, Schrading S, Leutner CC, et al: Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23:8469-8476, 2005 16. Lehman CD, Blume JD, Weatherall P, et al: Screening women at high risk for breast cancer with mammography and magnetic resonance imaging. Cancer 103:1898-1905, 2005 17. Saslow D, Boetes C, Burke W, et al: American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57:75-89, 2007 18. Saadatmand S, Tilanus-Linthorst MM, Rutgers EJ, et al: Cost-effectiveness of screening women with familial risk for breast cancer with magnetic resonance imaging. J Natl Cancer Inst 105:1314-1321, 2013 19. Sardanelli F, Podo F, D’Agnolo G, et al: Multicenter comparative multimodality surveillance of women at genetic-familial high risk for breast cancer (HIBCRIT study): Interim results. Radiology 242:698-715, 2007
DOI: 10.1200/JCO.2014.56.1514; published online ahead of print at www.jco.org on June 23, 2014
■ ■ ■
www.jco.org
© 2014 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on June 30, 2014. For personal use only. No other uses without permission. Copyright © 2014 American Society of Clinical Oncology. All rights reserved.
3
Editorial
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Rethinking Breast Cancer Screening: Ultra FAST Breast Magnetic Resonance Imaging The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Elizabeth A. Morris Honoraria: Bracco Diagnostics Consulting or Advisory Role: Genentech
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