Readers React: In defense of breast density notification laws

We read with interest the article “Breast density laws: Are you in compliance?” [December 2016 Contemporary OB/GYN]. We appreciated the perspective of our gynecologist colleagues. We would like to help clarify and give context to some of the information in the article.

Breast density notification laws were developed and enacted specifically because of strong evidence about the limitations of mammography in women with dense breast tissue and the demonstrated benefits of supplemental screening in them. The laws vary by state, although there are efforts to develop a national standard. It is important that radiologists, primary care physicians, and ob/gyns work together to implement breast density notification as effectively as possible.

The authors state, “These [breast density notification] laws … in general … are not supported by known clinical facts.” Later, they state, “The American College of Obstetricians and Gynecologists (ACOG) Committee Opinion 625 … relates that … no studies have demonstrated earlier detection or improved prognosis when additional breast imaging is obtained in patients with mammographically dense breasts.” It is important to revisit the literature, because increasingly strong evidence supports supplemental screening.

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Randomized controlled trials have proven reduction in breast cancer mortality due to mammography screening.^1-3 Importantly, the trials in which screening produced a shift to diagnosis of earlier-stage breast cancer, especially node-negative invasive cancer, are the ones that demonstrated improved outcomes.^4,5 However, not all women benefit equally from mammographic screening. Interval cancers are those detected because of symptoms (such as a lump) during the interval between recommended screens. An interval cancer rate of more than 10% of cancers detected suggests the screening strategy is inadequate. In women with dense breasts, the interval cancer rate after mammographic screening is often more than 30% of all cancers, versus less than 10% in women with fatty breasts. Other modalities that improve detection of node-negative invasive cancer and reduce the interval cancer rate in women with dense breasts are expected to improve patient outcomes. Unfortunately, long-term mortality trials of supplemental screening would be prohibitively expensive and suffer from technology migration.

Benefits of screening mammography are reduced in women with dense breasts.⁶ Women with dense breasts are more likely to develop breast cancer, and breast cancer without calcifications can be masked by areas of dense tissue.⁷

Case 2 presented in the December article is an unlikely scenario because calcifications would typically be seen early (often in ductal carcinoma in situ component) even in dense breasts.

Earlier cancer detection by supplemental MRI

Based on multiple prospective international studies, supplemental screening with magnetic resonance imaging (MRI) has been recommended since 2007 for women at high risk for breast cancer beginning at age 25–30⁸: a) in those with known or suspected pathogenic mutation in BRCA1 or BRCA2 or other less common disease-causing mutations; b) in those with a 20%–25% lifetime risk of breast cancer based on models that assess risk of mutations; and c) in women with a history of chest radiation therapy before age 30 and at least 8 years earlier. High-risk women have been shown to have more advanced disease at diagnosis and interval cancer rates as high as 50% with mammographic screening alone.^9-11

Recommendations for annual supplemental screening with MRI (to begin by age 25–30 in such women) are independent of breast density and are based on many studies showing improved detection of early-stage breast cancer using MRI in high-risk women (with supplemental cancer detection rates after mammography averaging over 10 per 1000).¹²

Importantly, Warner et al. showed increased detection of node-negative invasive cancer and reduction in late-stage disease among women with known pathogenic BRCA mutations who were screened with MRI compared to those who were not screened with MRI.¹³ An analysis of large studies of MRI in 3 countries showed low rates of interval cancers of 10% or less even among high-risk women when screened with MRI in addition to mammography.¹⁴

Improved detection of early breast cancers with good prognosis has been shown with MRI even for average-risk women.¹⁵ An abbreviated or “fast” MRI using only a few of the standard sequences can be performed with comparable accuracy to the full diagnostic protocol¹⁶ and at much lower cost and may make use of MRI more accessible to women whose only risk factor is dense breasts. This is currently under investigation by the American College of Radiology Imaging Network (ACRIN).

NEXT: Earlier detection by supplemental ultrasound

Earlier cancer detection by supplemental ultrasound

Results from trials involving more than 100,000 women using supplemental screening ultrasound have been published and consistently show added detection (after mammography) of 3-4 cancers per 1000 women screened, with such results maintained each year in the ACRIN 6666 study.¹⁷ Importantly, more than 85% of cancers found with screening ultrasound are node-negative invasive cancers.¹⁸ In the randomized prospective trial of screening ultrasound in Japan (J-START), detection of node-negative invasive cancers was significantly increased and the interval cancer rate was cut in half among women having screening ultrasound.¹⁹

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Tomosynthesis (3D mammography) improves cancer detection over standard mammography (1–2 more cancers per 1000 women screened) but this benefit does not appear to extend to women with extremely dense breasts.²⁰ In practice at the University of Pittsburgh Medical Center, we recommend tomosynthesis for all women and supplemental screening with ultrasound for women with extremely dense breasts. We limit our recommendation for ultrasound to those women with extremely dense breasts only because of our limited capacity to perform screening ultrasound; screening ultrasound is performed on request in women with heterogeneously dense breasts. Women at high risk should have supplemental MRI instead of ultrasound. In high-risk women with dense breasts who are unable to have or tolerate MRI, supplemental ultrasound is recommended.²¹

Insurance coverage for supplemental screening

Insurance covers supplemental screening with ultrasound in women with dense breasts (ICD10 code R92.2), but, in states without mandatory insurance coverage, this is subject to a deductible and copay and the resulting out-of-pocket cost is typically $100–$125. In women at high risk, most insurers will cover supplemental screening with MRI (regardless of breast density), but again it is subject to a copay or deductible except in a few states. In a few states (Connecticut, Illinois, Indiana, and New York), if a patient and her provider reach the decision to pursue further screening, insurance coverage is mandated (though not necessarily without a copay or deductible). In New Jersey, such coverage is mandated only for women with extremely dense breasts.

Density legislation

• Connecticut’s law requires women be provided general information about breast density, but does not require a woman be told her breasts are dense or information about her personal breast density category. New York’s law, effective January 19, 2013, was the first to require that a woman receive information about her own breast density.

• Twenty-seven states require some level of breast density notification (see interactive map at Dense-Breast-info.org: http://densebreastinfo.org/legislation.aspx). Indiana also has a law on this topic but the language is vague.

• No state density information law “mandates” offering supplemental breast screening although many recommend that women discuss additional screening with their doctors.

• No state law requires a referring physician to contact a patient to discuss breast density. Some state laws direct the woman to contact her doctor with any questions or for further discussion.

References

1. Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(10):727-37, W237-42.

2. Coldman A, Phillips N, Wilson C, et al. Pan-canadian study of mammography screening and mortality from breast cancer. J Natl Cancer Inst. 2014;106(11).

3. Tabar L, Yen MF, Vitak B, Chen HH, Smith RA, Duffy SW. Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening. Lancet. 2003;361(9367):1405-10.

4. Tabar L, Yen AM, Wu WY, et al. Insights from the breast cancer screening trials: how screening affects the natural history of breast cancer and implications for evaluating service screening programs. Breast J. 2015;21(1):13-20.

5. Smith RA, Duffy SW, Gabe R, Tabar L, Yen AM, Chen TH. The randomized trials of breast cancer screening: what have we learned? Radiol Clin North Am. 2004;42(5):793-806.

6. van der Waal D, Ripping TM, Verbeek AL, Broeders MJ. Breast cancer screening effect across breast density strata: A case-control study. Int J Cancer. 2016.

7. Harvey JA, Bovbjerg VE. Quantitative assessment of mammographic breast density: relationship with breast cancer risk. Radiology. 2004;230(1):29-41.

8. 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. 2007;57(2):75-89.

9. Tilanus-Linthorst M, Verhoog L, Obdeijn IM, et al. A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography. Int J Cancer. 2002;102(1):91-5.

10. Komenaka IK, Ditkoff BA, Joseph KA, et al. The development of interval breast malignancies in patients with BRCA mutations. Cancer. 2004;100(10):2079-83.

11. Brekelmans CT, Seynaeve C, Bartels CC, et al. Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. J Clin Oncol. 2001;19(4):924-30.

12. Berg WA. Tailored supplemental screening for breast cancer: what now and what next? AJR Am J Roentgenol. 2009;192(2):390-9.

13. Warner E, Hill K, Causer P, et al. Prospective study of breast cancer incidence in women with a BRCA1 or BRCA2 mutation under surveillance with and without magnetic resonance imaging. J Clin Oncol. 2011;29(13):1664-9.

14. Heijnsdijk EA, Warner E, Gilbert FJ, et al. Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined. Cancer Epidemiol Biomarkers Prev. 2012;21(9):1458-68.

15. Schrading S, Strobel K, Kuhl CK. MRI screening of women at average risk of breast cancer. San Antonio Breast Cancer Symposium. San Antonio, TX, 2013.

16. Kuhl CK, Schrading S, Strobel K, Schild HH, Hilgers RD, Bieling HB. Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection-a novel approach to breast cancer screening with MRI. J Clin Oncol. 2014;32(22):2304-10.

17. 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. 2012;307(13):1394-404.

18. Berg WA. Screening Ultrasound. In: Berg WA, Yang WT, eds. Diagnostic Imaging: Breast, 2nd ed. Salt Lake CIty: Amirsys, 2014; p. 9:38-43.

19. Ohuchi N, Suzuki A, Sobue T, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anticancer Randomized Trial (J-START): a randomised controlled trial. Lancet. 2015.

20. Rafferty EA, Durand MA, Conant EF, et al. Breast cancer screening using tomosynthesis and digital mammography in dense and nondense breasts. JAMA. 2016;315(16):1784-6.

21. Lee CH, Dershaw DD, Kopans D, et al. Breast cancer screening with imaging: recommendations from the Society of Breast Imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and other technologies for the detection of clinically occult breast cancer. J Am Coll Radiol. 2010;7(1):18-27.

22.Harvey J. Breast density websites: where to send your patients and referring providers for information. Society of Breast Imaging Member Newsletter, August 2016 Issue 3. http://densebreast-info.org/img/sbibreastdensitywebsites_jenniferharveymd.pdf