Imaging Management of Breast Density, a Controversial Risk Factor for Breast Cancer

Reduced sensitivity rates of mammography due to masking alone do not explain the increased risk of breast cancer associated with increased breast density. First described in 1976, Wolfe⁴ identified breast density as a risk factor for breast cancer, qualitatively evaluating the mammographic appearance of the breast. A direct relationship was reported between progressively dense breast tissue and increasing risk of breast cancer.³ McCormack et al⁵ performed a meta-analysis of 42 studies and found that increased breast density was a strong risk factor for breast cancer independent of other known risk factors but was confounded by age and body mass index. The risk of breast malignancy associated with dense breasts has been reported to be 4- to 6-fold, making it second only to age and BRCA carrier status for highest risk.^3,6 However, critics argue that this assessment of risk is an overestimation.² The studies compared extremes (ie, dense breasts to fatty breasts) rather than comparing dense breasts to average-density breasts (between scattered fibroglandular and heterogeneously dense tissue).² When the risk for breast cancer is expressed relative to average breast density, the risk decreases to 1.2 to 2.1 times higher than the average for heterogeneously dense or extremely dense breasts, respectively.² Thus, breast density may more accurately represent a modest risk factor similar to that for a woman with 1 first-degree relative with unilateral postmenopausal breast cancer.²

Awareness is increasing among public and medical communities alike regarding breast density as a risk factor for breast cancer as well as the limitations of mammography in women with dense breasts.^2,7 Thus, in 2009, Connecticut became the first state to mandate patient and referring physician notification of dense breasts, as determined by the interpreting radiologist. Since then, 26 states have enacted similar notification laws, and legislation has been introduced in several other states.⁸ Controversy surrounds these notification laws, particularly with regard to how notification relates to additional imaging and reimbursement.

Price et al² identified the efficacy, benefits, and harms of supplemental screening tests as key issues. Although notification increases patient awareness, it also increases patient anxiety.^9,10 Conversely, notification may give a false sense of security to women with fatty breasts who receive a negative finding on mammography.¹⁰ Critics also raise concerns that notification will increase demand for additional screening beyond mammography, which could result in additional false-positive findings and increased health care costs.¹⁰ Five states have mandatory insurance coverage for supplemental screening, suggesting that disparities could develop between women who can afford additional screening and those who cannot.^8,10,11 In a study performed in New Jersey after the implementation of legislation directed at notifying women of their breast density — which also mandated health insurance coverage — an increase was seen in patients utilizing screening ultrasonography, thus resulting in an expansion of the ultrasonography department at the New Jersey institution as well as increasing the direct cost for health care insurers of approximately $4.9 million to $9.8 million for a given month.⁷

Thus, as notification laws gain momentum, clinicians may be faced with new challenges in their approach to breast cancer screening in women with dense breasts. In this review, we address the available types of supplemental screening studies, the risks and benefits of each modality, and suggest an imaging approach to managing the imaging of dense breasts.

Screening Mammography and Tomosynthesis

Mammography has long been the mainstay of detecting breast cancer and is the only screening test proven to reduce breast cancer–related mortality.¹² Early detection by mammography has reduced breast cancer–related mortality by up to 30% — a rate based on several large, randomized controlled trials with 10 to 20 years of follow-up time.^12,13 The overall sensitivity rate of digital mammography is between 81% and 87% for the detection of breast cancer in women aged 40 to 79 years; the detection rate of cancer via mammography is 4 to 5 per 1,000 people in the average population.¹⁴

However, mammography is an imperfect screening tool. Although it remains the gold standard for breast cancer screening, awareness is increasing that mammography has reduced sensitivity in certain subpopulations of women. In particular, among women with dense breasts, tissue superimposition can occur to a greater degree,¹⁴ and 50% of cancers will be visible in extremely dense breast tissue.¹⁵ Among women with heterogeneously dense or extremely dense breast parenchyma, full-field digital mammography (FFDM) has been shown to be more sensitive than film-screen mammography.¹⁶ The sensitivity rates of both digital and analog mammography remain low in women with dense breast parenchyma, thus limiting its usefulness in younger women at high risk.^17,18

Digital breast tomosynthesis is an emerging technology utilized by many breast imaging centers, both domestically and internationally. Digital breast tomosynthesis was approved in February 2011 as an adjunct screening tool.¹⁹ It is an FFDM system capable of producing standard 2-dimensional (2D) and 3-dimensional (3D) tomosynthesis imaging. Digital breast tomosynthesis can help improve the detection and characterization of lesions by minimizing the influence of tissue overlap in women with nonfatty breasts. To acquire the image, the tube moves in an arc across the breast, and a series of low-dose scans are obtained from different angles. Typically, the imaging is then reconstructed into thin, 1-mm slices that can be scrolled through slice by slice — similar to that seen in computed tomography. Thin-slice imaging allows the clinician to better detect lesions, particularly masses, architectural distortions, and asymmetries (Figure 2).²⁰ Increased lesion conspicuity is beneficial when imaging dense breast tissue because it can be difficult for the clinician to detect lesions in extremely dense breast tissue.