RSNA, 2013 Appendix E1 Frequently Asked Questions about Breast Density, Breast Cancer Risk, and the Breast Density Notification Law in California: A Consensus Document 1. I have been getting more questions recently about breast cancer screening and dense breasts. Why? The California legislature recently passed a law requiring that women who have screening mammograms be informed if they have dense breast tissue. Specifically, women who have dense breast tissue will receive the following statement in writing as part of their mammogram result: Your mammogram shows that your breast tissue is dense. Dense breast tissue is common and is not abnormal. However, dense breast tissue can make it harder to evaluate the results of your mammogram and may also be associated with an increased risk of breast cancer. This information about the results of your mammogram is given to you to raise your awareness and to inform your conversations with your doctor. Together, you can decide which screening options are right for you. A report of your results was sent to your physician. 2. Why is this new? I thought that mammogram results always included information about density. Radiologists have routinely reported the breast density as part of their interpretation for years, which is in the report sent to the patient s physician or available on an electronic medical database. However, up until now, it has not been a part of the standard letter that women receive when their mammogram is negative. 3. How common is it to have dense breasts? Breast density is essentially the ratio of fat to fibroglandular tissue in the breast. Radiologists characterize each mammogram into one of four levels of overall density. Based on population studies, and listed in order of least dense to most dense, the frequency distribution of these categories is approximately as follows: almost entirely fatty, 10%; scattered areas of fibroglandular density, 40%; heterogeneously dense, 40%; and extremely dense, 10%. All women who fall into the latter two categories (heterogeneously dense and extremely dense) will be informed that they have dense breasts under the law. Therefore, approximately 50% of women will fall into these two categories and be told that they have dense breasts. Currently, the determination of density by radiologists is a qualitative, visual assessment. Evolving technologies may provide more objective and quantitative density assessment in the future. 4. What is the significance of mammographic breast density? There are two primary implications of mammographic breast density. One implication is the effect on mammographic sensitivity (ie, the test s ability to identify a clinically occult malignancy); this concept is known as masking. The second implication is the increase in breast cancer risk imparted by dense breasts. Both these implications are described below. Overall, the Page 1 of 8
potential masking effect of breast density is likely of greater import than the minor increase in breast cancer risk. 5. How high is the cancer risk associated with breast density? Consider the risk that an average woman will be diagnosed with breast cancer during the next 10 years of her life: Age 30: 0.44% (1 in 227) Age 40: 1.47% (1 in 68) Age 50: 2.38% (1 in 42) Age 60: 3.56% (1 in 28) Age 70: 3.82% (1 in 26) The medical literature on the impact of density on this cancer risk is often misleading because most studies describe the risk by comparing the 10% of women in the highest density category (extremely dense) with the 10% of women in the lowest density category (almost entirely fatty). This is not meaningful to the other 80% of women, nor should risk comparisons be related to such a small subset of the patient population. When risk is expressed relative to average breast density (between scattered areas of fibroglandular density and heterogeneously dense), the risk for the 40% of women with heterogeneously dense breasts is only about 1.2 times greater and the risk for the 10% of women with extremely dense breasts is only about 2 times greater. Therefore, breast density is not a major cancer risk factor. 6. What is masking and how frequently does breast density mask the visibility of nonpalpable cancer at screening mammography? Masking occurs when surrounding breast tissue obscures a cancer. The cancer is thus indiscernible mammographically, limiting the sensitivity of the screening test. While masking is not a substantial problem in patients with nondense breasts, mammographic sensitivity is diminished by up to 10% 20% in dense breasts. This is a major contributor to the drive for an additional screening modality to be used in conjunction with mammography. MR imaging has been demonstrated to be a useful screening tool in patients at very high risk for breast cancer. US and tomosynthesis are also being studied as potential supplemental screening modalities, with current results suggesting some increase in cancer detection with both modalities but increased false-positive findings for US compared with decreased false-positive findings for tomosynthesis. 7. Should my patients who receive this letter and have dense breasts continue to get mammograms? Yes. Mammography is the only screening tool that has been demonstrated through large randomized trials to lower breast cancer mortality. Those trials included all breast densities. Although mammography sensitivity is somewhat lower in women with extremely dense breasts, it is still the best modality for population-based screening. Also, mammography is the only test that can reliably detect suspicious calcifications. Such calcifications are often the first sign of in situ cancers, which (in 20% of cases) coexist with otherwise invisible invasive cancers. Page 2 of 8
8. If my patients with dense breasts want to have additional tests done, what are the screening options referred to in the new letter language? Among the additional tests that are available, screening breast MR imaging and screening breast US have been tested extensively. Background breast density has less impact on the ability of MR imaging and US to detect cancer than it does for mammography, which is why either of these tests increases cancer detection over mammography alone, MR imaging much more so than US. However, US is associated with a much higher rate of benign biopsies and both MR imaging and US result in a much higher rate of recommendation for short-interval follow-up than mammography. Therefore, choosing to have one of these tests in addition to mammography involves the benefit-risk trade-off of early cancer detection versus increased false-positive findings. The higher the cancer risk, the more likely there will be benefit, so the trade-off is more favorable for high-risk women than for average-risk women who simply have dense breasts. Screening breast tomosynthesis (sometimes referred to in advertising as 3D mammography ) is currently being introduced into some radiology practices, but its use has not been as completely studied as either MR imaging or US. Preliminary data suggest that tomosynthesis may increase breast cancer detection to about the same degree as US (although not as much as MR imaging) but that tomosynthesis may decrease rather than increase the rate of false-positive findings. As such, tomosynthesis ultimately may be shown to be a better screening test than standard mammography and may eliminate the need to consider supplementary screening with US. However, we await more robust evidence on the benefits and limitations of tomosynthesis. At this point, availability of tomosynthesis may be limited. 9. Are any supplemental screening tests recommended by radiologists for highrisk women? In high-risk women, supplemental screening tests are recommended in addition to mammography. Studies support the use of screening MR imaging in women who are known to have a very high risk (>20% lifetime or >5% 10 year) of breast cancer, regardless of their breast density. This examination is widely recommended by radiologists. Other studies have provided support for screening US for high-risk women, but only for those women with dense breasts who have not had MR imaging. If a woman undergoes screening MR imaging, screening US will provide no additional benefit. In addition, many centers either do not offer screening US or offer it with out-of-pocket charges to the patient. Although a more expensive test, screening breast MR imaging is generally covered for women who are at very high risk. There is no formal recommendation from the radiology community at this point regarding screening US. Some radiologists are opposed to it, while some believe that it has a role. 10. So if a woman has dense breasts, a risk assessment may be helpful? Perhaps. For the great majority of women informed that they have dense breasts under the law, breast density in itself has only a small impact on their overall risk. But there are other important risk factors that also may come into play, and knowing a specific patient s risk level can help determine whether supplemental screening is appropriate. If a woman is at very high risk, screening MR imaging would likely be helpful. Page 3 of 8
11. Approximately 50% of women who have a screening mammogram will be receiving letters including a statement suggesting consideration of other screening options. It is impossible for me to do a risk assessment on all of them. What do you suggest? If a woman requests supplemental breast screening, it may be possible to rapidly triage the need for a risk assessment. The strongest risk factors for breast cancer, other than age and sex, are personal or family history (especially a first-degree relative with premenopausal breast or ovarian cancer) and personal history of atypia at prior biopsy (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ). Although neither of these risks, nor dense breasts, individually place a woman in the very-high-risk category, they may identify those who would likely benefit from a full risk assessment with use of mathematic models such as Claus, BRCAPRO, Tyrer-Cuzick (IBIS Breast Cancer Risk Evaluation Tool), BOADICEA, and others. This is best conducted by someone who is fully informed on risk assessment procedures and who also can counsel the patient on the results. Clinicians who feel comfortable in this capacity can perform a risk assessment or refer the patient to a cancer risk assessment program. For patients who have had mantle radiation therapy at an age younger than 30 years or who have previously tested positive for the BRCA1 or BRCA2 gene mutations or other genetic syndromes, screening breast MR imaging is recommended annually in addition to mammography. Of note, gene mutation testing is not a requirement to be considered an appropriate candidate for MR imaging screening. If a woman tests negative for BRCA gene mutation but has strong family history, she may still need MR imaging screening. 12. I have a patient with dense breasts who desires supplemental screening. She is not at very high breast cancer risk and/or has no major risk factors. What should I recommend? Screening MR imaging has not been studied in average-risk women with no known cancer diagnosis. However, if a patient expresses a desire to be screened with MR imaging, then a full risk assessment would be helpful. Even if a patient does not have strong risk factors for breast cancer, there are a number of minor risk factors, including breast density, which together may raise her to a sufficiently high risk. The American Cancer Society states that for intermediate risk women, with a 15% 20% lifetime risk (this may include women with a history of atypia at biopsy or those with a personal history of breast cancer), the decision to have a screening MR imaging should be made on a case-by-case basis by using a shared decision-making approach. The data on screening US is limited at this point. Mammography typically finds six to eight breast cancers in every 1000 women screened for the first time. In women with dense breasts at average risk, small studies have shown US can depict 1.6 4 mammographically occult cancers for every 1000 women screened for the first time. Therefore, supplemental US adds substantially to the cancer yield in some studies. The majority of cancers found at US are smaller than 1 cm and are invasive. However, there are two major drawbacks to the currently available data. The first is that no studies have been performed with control groups and long-term follow-up. Thus, we do not know what the clinical impact of finding these additional small cancers is specifically whether the cancers would otherwise be detected at the next mammography screen while still small, node-negative, and at an early stage and whether there is any impact on mortality. The second Page 4 of 8
drawback is that many more biopsies are generated by screening US than screening mammography, and most of these additional biopsy recommendations ultimately end up being false-positive findings. The positive biopsy rate for lesions detected at screening mammography is 25% 40%, whereas the positive biopsy rate for lesions found at screening US is 5% 10%. This means that 90% 95% of biopsies initiated by the screening US in women with negative mammograms end up showing no cancer. Due to these concerns, there is no formal recommendation from the radiology community at this point regarding screening US. Some radiologists are opposed to it, while some believe that it has a role. The results of screening breast US may be more favorable in centers with a dedicated program. Whichever supplemental screening test is being considered, it is important to keep in mind that for patients who are not high risk, the a priori probability of breast cancer is low. Therefore, the benefit of additional screening is diminished, whereas the potential harms remain the same. 13. What about tomosynthesis ( 3D mammography )? Tomosynthesis uses similar technology to conventional mammography and many centers are currently in the process of adopting it because it has shown promising early results. Recent data suggest that, in general, tomosynthesis reduces false-positive findings and may also permit detection of additional cancers in the screening population. Because some centers are starting to use tomosynthesis routinely in screening examinations, some women in California who have tomosynthesis at screening will receive patient letters stating that they have dense breasts. For these women, the primary physician may want to inform them that they have already had a supplemental test. However, we do not yet know how well tomosynthesis performs, particularly in the small group of women with extremely dense breasts, and the previous discussion about US and MR imaging still applies. The radiation dose of the combined digital plus 3D mammography examination (as is required for all tomosynthesis examinations) is approximately double that of standard digital mammography alone. However, this dose still falls below U.S. FDA limits and dose reduction strategies are being actively developed. In particular, the use of synthesized digital mammographic images created from 3D data has received recent FDA approval, resulting in substantial dose reduction. Thus, the dose-related risk implications for women are considered acceptable. 14. What will the cost of supplemental screening tests be to my patient and to the health care system? The California legislature did not mandate insurance coverage for any supplemental breast cancer screening tests. Currently, there are no insurance billing codes for screening breast US or tomosynthesis. Screening breast MR imaging is usually covered for high-risk women but may not be for women at average risk who simply have dense breasts. As such, women who desire certain types of supplemental screening may be asked to pay out of pocket. From a societal perspective, supplemental screening of the approximately 50% of California women with dense breasts would result in very substantial additional cost to the health care system. Page 5 of 8
Take Home Points Starting April 1, 2013, California law requires that patients be informed if they have dense breast tissue at screening mammography, and, if so, that they may want to discuss their screening options with their primary physician. Approximately 50% of women undergoing screening mammography are classified as having either heterogeneously dense or extremely dense breasts. For all of these women, the patient letter will inform that they have dense breast tissue. Only 10% of all women have extremely dense breast tissue, which is associated with a relative risk of breast cancer of approximately 2 compared with average breast density. 40% of women have heterogeneously dense breast tissue, which is associated with a relative risk of approximately 1.2. Therefore, breast density is not a major cancer risk factor. The sensitivity of mammography is reduced as background breast tissue density increases. When mammography is the only screening test performed, sensitivity decreases by 10% 20% for women with dense breasts. The recommendations for screening mammography are exactly the same for women with dense breasts as for the rest of the population. Mammography is the only screening modality that has undergone randomized controlled trials demonstrating a reduction in breast cancer mortality. There is no recommendation that it be replaced with another test in any subset of the population. For patients who are interested in additional screening options, a breast cancer risk assessment may be appropriate. It is a good starting point in the discussion of whether supplemental tests will be beneficial and what tests, if any, to order. The other breast imaging screening options include screening MR imaging, US, and tomosynthesis ( 3D mammography ). Screening breast MR imaging has been shown to substantially increase the rate of cancer detection. It is recommended in patients who are at very high risk (>20% lifetime risk) based on American Cancer Society guidelines. For patients at intermediate risk, such as those with a personal history of breast cancer or a prior biopsy diagnosis of atypia (equivalent to a 15% 20% lifetime risk), a patientcentered shared decision-making approach is recommended. Screening breast US is not offered at many centers and may entail an out-of-pocket charge to patients. Small studies have shown a modest increase in cancer detection, but also a high rate of false-positive findings resulting in benign biopsies. The choice to have this test should be made on an individual basis after a discussion of these risks, benefits, and costs. Breast tomosynthesis ( 3D mammography ) is being offered in addition to screening mammography in some centers. Thus far, we have preliminary encouraging data on the performance of tomosynthesis in women with dense tissue. Reading List 1. American College of Radiology. Breast Imaging Reporting and Data System (BI-RADS) 5. Reston, Va: American College of Radiology (in press). Page 6 of 8
2. Berg WA, Blume JD, Cormack JB, et al. Combined screening with ultrasound and mammography versus mammography alone in women at elevated risk of breast cancer. JAMA 2008;299:2151 2163. 3. Berg WA, Zhang Z, Lehrer D, et al. Detection of breast cancer with addition of annual screening ultrasound or a single screening MR imaging to mammography in women with elevated breast cancer risk. JAMA 2012;307:1394 1404. 4. Bevers TB, Anderson BO, Bonaccio E, et al. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis. J Natl Compr Canc Netw 2009;7(10):1060 1096. 5. Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. New Engl J Med 2007;356:227 236. 6. Buist DS, Porter PL, Lehman C, Taplin SH, White E. Factors contributing to mammography failure in women aged 40 49 years. J Natl Cancer Inst 2004;96:1432 1440. 7. Carney PA, Miglioretti DL, Yankaskas BC, et al. Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Ann Intern Med 2003;138:168 175. 8. Hooley RJ, Greenberg KL, Stackhouse RM, Geisel JL, Butler RS, Philpotts LE. Screening US in patients with mammographically dense breasts: initial experience with Connecticut Public Act 09 41. Radiology 2012;265:59 69. 9. Kelly KM, Dean J, Comulada WS, Lee SJ. Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts. Eur Radiol 2010;20:734 742. 10. 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 2010;28:1450 1457. 11. Mainiero MB, Lourenco A, Mahoney MC, et al. ACR Appropriateness Criteria Breast Cancer Screening. J Am Coll Radiol 2013;10:11 14. 12. Pinsky RW, Helvie MA. Mammographic breast density: effect on imaging and breast cancer risk. J Natl Compr Canc Netw 2010;8:1157 1164; quiz 65. 13. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MR imaging as an adjunct to mammography. CA Cancer J Clin 2007;57(2):75 89. 14. Schousboe JT, Kerlikowske K, Loh A, Cummings SR. Personalizing mammography by breast density and other risk factors for breast cancer: analysis of health benefits and costeffectiveness. Ann Intern Med 2011;155:10 20. 15. Sickles EA. The use of breast imaging to screen women at high risk for cancer. Radiol Clin North Am 2010;48:859 878. Page 7 of 8
16. Skaane P, Bandos AI, Gullien RT, et al. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology 2013;267(1):47 56. 17. Smith RA, Brooks D, Cokkinides V, Saslow D, Brawley OW. Cancer screening in the United States, 2013. CA Cancer J Clinic 2013;63(2):87 105. 18. Tice JA, Cummings SR, Smith-Bindman R, Ichikawa L, Barlow WE, Kerlikowske K. Using clinical factors and mammographic breast density to estimate breast cancer risk: development and validation of a new predictive model. Ann Intern Med 2008;148:337 347. 19. Vachon CM, van Gils CH, Sellers TA, et al. Mammographic density, breast cancer risk and risk prediction: breast cancer research. BCR 2007;9:217. 20. van Gils CH, Otten JD, Verbeek AL, Hendriks JH. Mammographic breast density and risk of breast cancer: masking bias or causality? Eur J Epidemiol 1998;14:315 320. 21. Whitehead J, Carlile T, Kopecky KJ, et al. Wolfe mammographic parenchymal patterns: a study of the masking hypothesis of Egan and Mosteller. Cancer 1985;56:1280 1286. Appendix E2 Notification Legislation Under the aegis of the U.S. Mammography Quality Standards Act (MQSA), women receive a lay letter informing them of their mammogram result. California s breast density notification law requires that the following statement be included in the letter for women determined to have heterogeneously or extremely dense breasts: Your mammogram shows that your breast tissue is dense. Dense breast tissue is common and is not abnormal. However, dense breast tissue can make it harder to evaluate the results of your mammogram and may also be associated with an increased risk of breast cancer. This information about the results of your mammogram is given to you to raise your awareness and to inform your conversations with your doctor. Together, you can decide which screening options are right for you. A report of your results was sent to your physician. Page 8 of 8