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.