North Carolina Passes Breast Density Law

North Carolina is the 12th state to enact a breast density notification law.

The North Carolina legislature passed a law (Session Law 2013-321) requiring that all women who have mammograms be informed of their breast tissue type.  Specifically, women who have dense breast tissue will receive the following statement in writing as part of their mammogram result:

“Your mammogram indicates that you may have dense breast tissue. Dense breast tissue is relatively common and is found in more than forty percent (40%) of women. The presence of dense tissue may make it more difficult to detect abnormalities in the breast and may be associated with an increased risk of breast cancer. We are providing this information to raise awareness of this important factor and to encourage you to talk with your physician about this and other breast cancer risk factors. Together, you can decide which screening options are right for you. A report of your results was sent to your physician.”

The new law became effective on January 1, 2014

Question: I have been getting more questions recently about breast cancer screening and dense breasts. Why?

Answer: The North Carolina legislature recently passed a law (Session Law 2013-321) requiring that women who have mammograms be informed of their breast tissue type. Specifically, women who have dense breast tissue will receive the following statement in writing as part of their mammogram result:

“Your mammogram indicates that you may have dense breast tissue. Dense breast tissue is relatively common and is found in more than forty percent (40%) of women. The presence of dense tissue may make it more difficult to detect abnormalities in the breast and may be associated with an increased risk of breast cancer. We are providing this information to raise your awareness of this important factor and to encourage you to talk with your physician about this and other breast cancer risk factors. Together, you can decide which screening options are right for you. A report of your results was sent to your physician.”

Question: Why is this new? I thought that mammogram results always included information about density.

Answer: 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.

Breast Density Definitions

Question: How common is it to have dense breasts?

Answer: 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: 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.

Question: What is the significance of mammographic breast density?

Answer: There are two primary implications of mammographic breast density. One implication is the effect on mammographic sensitivity (i.e., 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 potential masking effect of breast density is likely of greater import than the minor increase in breast cancer risk.

Breast Density and Risk

Question: How high is the cancer risk associated with breast density?

Answer: 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.

Masking

Question: What is masking and how frequently does breast density mask the visibility of non-palpable cancer at screening mammography?

Answer: 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 non-dense 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. MRI has been demonstrated to be a useful screening tool in patients at very high risk for breast cancer. Ultrasound and tomosynthesis are also being studied as potential supplemental screening modalities, with current results suggesting some increase in cancer detection using both modalities, but increased false positives for ultrasound compared to decreased false positives for tomosynthesis

Importance of Mammograms

Question: Should my patients who receive this letter and have dense breasts continue to get mammograms?

Answer: 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. While 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.

Supplemental Screening Options: a risk-based approach

Question: If my patients with dense breasts want to have additional tests done, what are the “screening options”?

Answer: Among the additional tests that are available, screening breast MRI and screening breast ultrasound have been tested. Background breast density has less impact on the ability of MRI and ultrasound to detect cancer than it does for mammography, which is why either of these tests increases cancer detection over mammography alone, MRI much more so than ultrasound. However, both MRI and ultrasound are associated with a much higher rate of benign biopsies and 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 positives. 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 MRI or ultrasound. Preliminary data suggest that tomosynthesis may increase breast cancer detection to about the same degree as ultrasound (although not as much as MRI), but that tomosynthesis may decrease rather than increase the rate of false positives. 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 ultrasound. However, we await more robust evidence on the benefits and limitations of tomosynthesis. At this point, availability of tomosynthesis may be limited.

Question: Are any supplemental screening tests recommended by radiologists for high risk women?

Answer: In high risk women, supplemental screening tests are recommended in addition to mammography. Studies support the use of screening MRI 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 ultrasound for high-risk women, but only for those women with dense breasts who have not had MRI. If a woman has a screening MRI, screening ultrasound will provide no additional benefit. In addition, many centers either do not offer screening ultrasound or offer it with out-of-pocket charges to the patient. Although a more expensive test, screening breast MRI 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 ultrasound. Some radiologists are opposed to it, while some believe that it has a role.

Question: So if a woman has dense breasts, a risk assessment may be helpful?

Answer: 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 to determine whether supplemental screening is appropriate. If a woman is at very high risk, a screening MRI would likely be helpful.

Question: It is impossible for me to do a risk assessment on all of them. What do you suggest?

Answer: 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 on prior biopsy (ADH, ALH, LCIS). While 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, using mathematical 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 on to a cancer risk assessment program.

For patients who have had mantle radiation therapy at age <30, or who have previously tested positive for the BRCA1 or BRCA2 gene mutations or other genetic syndromes, screening breast MRI is recommended annually in addition to mammography. Of note, gene mutation testing is not a requirement to be considered an appropriate candidate for MRI screening. If a woman tests negative for BRCA gene mutation but has strong family history, she may still need MRI screening.

Question: 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?

Answer: Screening MRI has not been studied in average-risk women with no known cancer diagnosis. However, if a patient expresses a desire to be screened with MRI, 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 on biopsy or with a personal history of breast cancer), the decision to have a screening MRI should be made on a case-by-case basis using a shared decision-making approach.

The data on screening ultrasound is limited at this point. Mammography typically finds 6 to 8 breast cancers in every 1000 women screened for the first time. In women with dense breasts at average risk, small studies have shown ultrasound can detect 1.6 to 4 mammographically occult cancers for every 1000 women screened for the first time. Therefore, supplemental ultrasound adds substantially to the cancer yield in some studies. The majority of cancers found on ultrasound 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 early stage, and whether there is any impact on mortality. The second drawback is that many more biopsies are generated by screening ultrasound than screening mammography, and most of these additional biopsy recommendations ultimately end up being false positives. The positive biopsy rate for lesions detected on screening mammography is 25% to 40%, while the positive biopsy rate for lesions found on screening ultrasound is 5-10%. This means that 90% to 95% of biopsies initiated by the screening ultrasound 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 ultrasound. Some radiologists are opposed to it, while some believe that it has a role. The results of screening breast ultrasound 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.

Question: What about tomosynthesis (“3D mammography”)?

Answer: 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 exams, some women in North Carolina 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 ultrasound andMRIstill applies.

Question: What will the cost of supplemental screening tests be to my patient and to the healthcare system?

Answer: The North Carolina legislature did not mandate insurance coverage for any supplemental breast cancer screening tests. Currently, there are no insurance billing codes for screening breast ultrasound or tomosynthesis. Screening breast MRI 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 percent of North Carolina women with dense breasts would result in very substantial additional cost to the health care system.

Take Home Points

• Starting January 1, 2014, North Carolina law requires that all patients who have a mammogram be informed of their breast tissue density, and if they have “dense breast tissue”, 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 them 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% to 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 MRI, ultrasound and tomosynthesis (“3D mammography”). Screening breast MRI 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% to 20% lifetime risk), a patient-centered shared decision-making approach is recommended.
• Screening breast ultrasound 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 positives 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.

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